Efficacy and Safety of Co-administration of Cagrilintide s.c. 2.4 mg and Semaglutide s.c. 2.4 mg Once Weekly in Subjects With Type 2 Diabetes
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Sponsor: Novo Nordisk A/S

C o v e r  P a g e  f o r P r ot o c ol  
 
S p o ns or  n a m e:  
N o v o  N or dis k  A/ S  
N C T  n u m b er  
N C T 0 4 9 8 2 5 7 5  
S p o ns or t ri al I D: 
N N 9 8 3 8 -4 8 6 2  
Offi ci al titl e  of st u d y:   
Effi c a c y  a n d s af et y  of  c o -a d mi nistr ati o n  of  c a grili nti d e s. c.  2. 4  
m g  a n d s e m a gl uti d e s. c.  2. 4  m g  o n c e  w e e kl y i n s u bj e cts  wit h 
t y p e  2  di a b et es 
D o c u m e nt  d at e *  
1 6  J u n e 2 0 2 1  
*  D o c u m e nt  d at e r ef ers t o t h e  d at e  o n  w hi c h t h e  d o c u m e nt  w as  m ost r e c e ntl y  u p d at e d.  
   N ot e:  T h e  d at e i n t h e  h e a d er  of  P a g e  2 is t h e  d at e  of  c o m pil ati o n  of t h e  d o c u m e nts  a n d  n ot  of  a n  u p d at e t o  c o nt e nt.  

Li n k
Li n k
List of c o nte nts
Pr ot oc ol ...............................................................................................................................................
1 6. 1. 0 1 St ate me nt Att ac h me nt I a n d II ............................................................................................
Date:
N o v o N or di s k
Versi o n:
Stat us:
Ca gri Se ma
Trial I D: N N 9 8 3 8 4 8 6 2
Cli nical Trial Re p ort
A p pe n di x 1 6. 1. 1
0 1 N o ve m ber 2 0 2 2
1. 0
Fi nal
1 6. 1. 1 Pr ot oc ol a n d pr ot oc ol a me n d me nts
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
Stat us:  
Fi n al  
P a ge:  
1  of 7 4  
Pr ot oc ol
Pr ot oc ol titl e:  Effic ac y a n d s afet y of c o -a d mi nistr ati o n of c a grili nti de s.c. 2. 4 m g a n d 
se m a gl uti de s.c. 2. 4 m g o nce wee kl y i n s u bjects wit h t y pe 2 di a betes  
S u bst a nce n a me: c a grili nti de, se m a gl uti de  
I N D N u m ber: 1 5 5 7 9 6 
U ni vers al Tri al N u m b er: U 1 1 1 1 -1 2 6 6 -2 9 3 1 
Tri al p h ase:  2  
I n t he f oll o wi n g, N o v o N or dis k A/ S a n d its affiliates will be state d as “ N o v o N or dis k”. 
   
   
   
   
    
  
  
   
   
   
   
   
 
 
   
   
   
   
   
   
   
   
    
   
   
 
   
    
 
 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
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C O N FI D E N TI A L
T his c o nfi de ntial d oc u me nt is t he pr o pert y of N o v o N or dis k. N o u n p u blis he d i nf or mati o n c o ntai ne d herei n ma y be 
discl ose d w it h o ut pri or writte n a p pr o val fr o m N o v o N or dis k. Access t o t his d oc u me nt m ust be restricte d t o rele va nt 
parties.

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2  of 7 4  
 
Ta ble of C o nte nts    
 
P a ge  
T a ble of C o nte nts .............................................................................................................................................. 2  
1  Pr ot oc ol s u m m ar y  ....................................................................................................................................... 5  
1. 1  
S y n o psis  .............................................................................................................................................. 5  
1. 2  
Fl o wc hart  ............................................................................................................................................ 8  
2  I ntr o d ucti o n ............................................................................................................................................... 1 0  
2. 1  
Trial rati o nale  .................................................................................................................................... 1 0  
2. 2  
Bac k gr o u n d  ....................................................................................................................................... 1 1  
2. 3  
Be nefit -ris k assess me nt ..................................................................................................................... 1 2  
2. 3. 1   
Ris k assess me nt  ................................................................................................................. 1 3  
2. 3. 2   
Be nefit assess me nt  ............................................................................................................. 1 6  
2. 3. 3   
O v erall be nefit -ris k c o ncl usi o n ......................................................................................... 1 6  
3  O bjecti ves a n d e n d p oi nts  .......................................................................................................................... 1 6  
3. 1  
Pri mar y, sec o n dar y a n d e x pl orat or y o bj ecti ve(s) a n d esti ma n d(s)  ................................................... 1 6  
3. 1. 1   
Pri mar y o bj ecti ves  ............................................................................................................. 1 6  
3. 1. 2   
Sec o n dar y o bj ecti ves  ......................................................................................................... 1 7  
3. 1. 3   
Esti ma n ds  .......................................................................................................................... 1 7  
3. 2  
Pri mar y, sec o n dar y a n d e x pl orat or y e n d p oi nt(s)  .............................................................................. 1 8  
3. 2. 1   
Pri mar y e n d p oi nt  ............................................................................................................... 1 8  
3. 2. 2   
Sec o n dar y e n d p oi nts  .......................................................................................................... 1 8  
3. 2. 2. 1   
C o nfir mat or y sec o n dar y e n d p oi nts  ................................................................ 1 8  
3. 2. 2. 2   
S u p p orti ve sec o n dar y e n d p oi nts  .................................................................... 1 8  
4  Tri al desi g n  ................................................................................................................................................ 1 9  
4. 1  
O verall desi g n  ................................................................................................................................... 1 9  
4. 2  
Scie ntific  rati o nale f or trial desi g n .................................................................................................... 1 9  
4. 3  
J ustificati o n f or d ose ......................................................................................................................... 2 0  
4. 4  
E n d of trial defi niti o n  ........................................................................................................................ 2 1  
5  Tri al p o p ul ati o n  ......................................................................................................................................... 2 1  
5. 1  
I ncl usi o n criteria ............................................................................................................................... 2 1  
5. 2  
E xcl us i o n criteria .............................................................................................................................. 2 1  
5. 3  
Lifest yle c o nsi derati o ns  .................................................................................................................... 2 2  
5. 3. 1   
Meals a n d dietar y restricti o ns  ............................................................................................ 2 3  
5. 3. 2   
Caffei ne, alc o h ol a n d t o bacc o  ........................................................................................... 2 3  
5. 4  
Scree n fail ures  ................................................................................................................................... 2 3  
5. 5  
R u n -i n criteria a n d/ or ra n d o misati o n criteria .................................................................................... 2 3  
6  Tre at me nts  ................................................................................................................................................. 2 3  
6. 1  
Treat me nts a d mi nistere d  ................................................................................................................... 2 3  
6. 1. 1   
Me dical de vices  ................................................................................................................. 2 6  
6. 2  
Pre parati o n/ ha n dli n g/st ora ge/acc o u nta bilit y  ..................................................................................... 2 6  
6. 2. 1   
S hi p me nt of trial pr o d uct t o s u bject’s h o me  ...................................................................... 2 7  
6. 3  
Meas ures t o mi ni mise bias: Ra n d o misati o n a n d bli n di n g ................................................................. 2 7  
6. 4  
Treat me nt c o m plia nce  ....................................................................................................................... 2 8  
6. 5  
C o nc o mita nt me dicati o n  ................................................................................................................... 2 8  
6. 5. 1   
Resc ue me dicati o n  ............................................................................................................. 2 9  
6. 6  
D ose m o dificati o n  ............................................................................................................................. 2 9  
6. 7  
Treat me n t after e n d of trial ............................................................................................................... 3 0  
7  Disc o nti n u ati o n of tri al tre at me nt a n d s u bject  disc o nti n u ati o n/ wit h dr a w al  ....................................... 3 0  
7. 1  
Disc o nti n uati o n of trial treat me nt  ..................................................................................................... 3 0  
7. 1. 1   
T e m p orar y disc o nti n uati o n of trial treat me nt  .................................................................... 3 1  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
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Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3  of 7 4  
 
7. 1. 2   
Resc ue criteria  ................................................................................................................... 3 1  
7. 2  
S u bj ect wit h dra wal fr o m t he trial ...................................................................................................... 3 1  
7. 2. 1   
Re place me nt of s u bjects  .................................................................................................... 3 2  
7. 3  
L ost t o f oll o w -u p ............................................................................................................................... 3 2  
8  Tri al assess me nts a n d pr oce d ures ............................................................................................................ 3 2  
8. 1  
Efficac y assess me nts  ......................................................................................................................... 3 3  
8. 1. 1   
B o d y meas ure me nts  ........................................................................................................... 3 3  
8. 1. 2   
C o nti n u o us gl uc ose m o nit ori n g  ......................................................................................... 3 3  
8. 1. 3   
Cli nical efficac y la b orat or y assess me nts  ........................................................................... 3 4  
8. 2  
Safet y assess me nts  ............................................................................................................................ 3 4  
8. 2. 1   
P h ysical e xa mi nati o ns  ....................................................................................................... 3 5  
8. 2. 2   
Vital si g ns  .......................................................................................................................... 3 5  
8. 2. 3   
Electr ocar di o gra ms  ............................................................................................................ 3 5  
8. 2. 4   
E ye e xa mi nati o n  ................................................................................................................ 3 5  
8. 2. 5   
Cli nic al safet y la b orat or y assess me nts  .............................................................................. 3 6  
8. 3  
A d verse e ve nts a n d seri o us a d verse e ve nts  ....................................................................................... 3 6  
8. 3. 1   
Ti me peri o d a n d fre q ue nc y f or c ollecti n g A E a n d S A E i nf or mati o n  ................................ 3 7  
8. 3. 2   
Met h o d of detecti n g A Es a n d S A Es  .................................................................................. 3 7  
8. 3. 3   
F oll o w -u p of A Es a n d S A Es  ............................................................................................. 3 7  
8. 3. 4   
Re g ulat or y re p orti n g re q uire me nts f or S A Es  .................................................................... 3 8  
8. 3. 5   
Pre g na nc y  .......................................................................................................................... 3 8  
8. 3. 6   
Car di o vasc ular a n d deat h e ve nts  ....................................................................................... 3 8  
8. 3. 7   
H y perse nsiti vit y  ................................................................................................................. 3 8  
8. 3. 8   
T ec h nical c o m plai nts  ......................................................................................................... 3 8  
8. 4  
Treat me nt of o ver d ose  ...................................................................................................................... 3 9  
8. 5  
P har mac o ki netics  .............................................................................................................................. 3 9  
8. 6  
P har mac o d y na mics  ........................................................................................................................... 3 9  
8. 7  
Ge netics  ............................................................................................................................................ 4 0  
8. 8  
Bi o mar kers  ........................................................................................................................................ 4 0  
8. 9  
I m m u n o ge nicit y assess me nts ............................................................................................................ 4 0  
8. 1 0  Healt h ec o n o mics  .............................................................................................................................. 4 0  
9  St atistic al c o nsi der ati o ns  .......................................................................................................................... 4 0  
9. 1  
Statistical h y p ot heses  ........................................................................................................................ 4 0  
9. 2  
Sa m ple size deter mi nati o n  ................................................................................................................ 4 0  
9. 3  
P o p ulati o ns f or a nal yses  ................................................................................................................... 4 1  
9. 4  
Statistical a nal yses  ............................................................................................................................ 4 2  
9. 4. 1   
Ge neral c o nsi derati o ns  ...................................................................................................... 4 2  
9. 4. 2   
Pri mar y e n d p oi nt  ............................................................................................................... 4 2  
9. 4. 3   
Sec o n dar y e n d p oi nt(s)  ....................................................................................................... 4 3  
9. 4. 3. 1   
C o nfir mat or y sec o n dar y e n d p oi nt(s)  .............................................................. 4 3  
9. 4. 3. 2   
S u p p orti ve sec o n dar y e n d p oi nts  .................................................................... 4 3  
9. 4. 4   
E x pl orat or y e n d p oi nts ........................................................................................................ 4 3  
9. 4. 5   
Ot her safet y a nal yses  ......................................................................................................... 4 3  
9. 4. 6   
Ot her a nal yses  ................................................................................................................... 4 3  
9. 4. 6. 1   
P har mac o ki netic m o delli n g  ............................................................................ 4 3  
9. 5  
I nteri m a nal yses ................................................................................................................................ 4 4  
9. 6  
Data m o nit ori n g c o m mittee  .............................................................................................................. 4 4  
9. 7  
Re p orti n g of t he mai n part of t he trial  ............................................................................................... 4 4  
1 0  S u p p orti n g d oc u me nt ati o n a n d o per ati o n al c o nsi der ati o ns .................................................................. 4 5  
1 0. 1  A p pe n di x 1: Re g ulat or y, et hical, a n d trial o versi g ht c o nsi derati o ns  ................................................ 4 5  
1 0. 1. 1  
Re g ulat or y a n d et hical c o nsi derati o ns  ............................................................................... 4 5  
1 0. 1. 2  
Fi na ncial discl os ure  ........................................................................................................... 4 5  
1 0. 1. 3  
I nf or me d c o nse nt pr ocess .................................................................................................. 4 5  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
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Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4  of 7 4  
 
1 0. 1. 4  
I nf or mati o n t o s u bj ects d uri n g trial ................................................................................... 4 6  
1 0. 1. 5  
Data pr otecti o n  .................................................................................................................. 4 6  
1 0. 1. 6  
C o m mittees str uct ure  ......................................................................................................... 4 7  
1 0. 1. 6 . 1  
N o v o N or dis k safet y c o m mittee ..................................................................... 4 7  
1 0. 1. 6. 2   
Trial safet y gr o u p  ........................................................................................... 4 7  
1 0. 1. 6. 3   
Data m o nit ori n g c o m mittee ............................................................................ 4 7  
1 0. 1. 6. 4   
E ve nt a dj u dicati o n c o m mittee  ........................................................................ 4 7  
1 0. 1. 7  
Disse mi nati o n of cli nical trial data  .................................................................................... 4 7  
1 0. 1. 8  
Data q ualit y ass ura nce  ....................................................................................................... 4 7  
1 0. 1. 8. 1   
Case re p ort f or ms  ........................................................................................... 4 7  
1 0. 1. 8 . 2  
M o nit ori n g  ..................................................................................................... 4 8  
1 0. 1. 8. 3   
Pr ot oc ol c o m plia nce  ....................................................................................... 4 8  
1 0. 1. 9  
S o urce d oc u me nts  .............................................................................................................. 4 9  
1 0. 1. 1 0  Re te nti o n of cli nical trial d oc u me ntati o n .......................................................................... 4 9  
1 0. 1. 1 1  Trial a n d site cl os ure .......................................................................................................... 4 9  
1 0. 1. 1 2  Res p o nsi bilities  .................................................................................................................. 5 0  
1 0. 1. 1 3  I n de m nit y state me nt .......................................................................................................... 5 1  
1 0. 1. 1 4  P u blicati o n p olic y  .............................................................................................................. 5 1  
1 0. 1. 1 4. 1  
C o m m u nicati o n of res ults  .............................................................................. 5 1  
1 0. 1. 1 4. 2  
A ut h ors hi p  ...................................................................................................... 5 2  
1 0. 1. 1 4. 3  
Si te-s pecific p u blicati o n(s) b y i n vesti gat or(s)................................................ 5 2  
1 0. 1. 1 4. 4  
I n vesti gat or access t o data a n d re vie w of res ults ........................................... 5 2  
1 0. 2  A p pe n di x 2: Cli nical la b orat or y tests ................................................................................................ 5 3  
1 0. 3  A p pe n di x 3: A d verse e ve nts: Defi niti o ns a n d pr oce d ures f or rec or di n g, e val uati o n, f oll o w -u p, 
a n d re p orti n g ..................................................................................................................................... 5 6  
1 0. 3. 1  
Defi niti o n of A E  ................................................................................................................ 5 6  
1 0. 3. 2  
Defi niti o n of a n S A E  ......................................................................................................... 5 6  
1 0. 3. 3  
Descri pti o n of A Es re q uiri n g a d diti o nal data c ollecti o n  ................................................... 5 7  
1 0. 3. 4  
Rec or di n g a n d f oll o w -u p of A E a n d/ or S A E  ..................................................................... 5 8  
1 0. 3. 5  
Re p orti n g of S A Es  ............................................................................................................. 6 0  
1 0. 4  A p pe n di x 4: C o ntrace pti ve g ui da nce a n d c ollecti o n of pre g na nc y i nf or mati o n  ............................... 6 2  
1 0. 4. 1  
Defi niti o ns  ......................................................................................................................... 6 2  
1 0. 4. 2  
C o ntrace pti o n g ui da nce  ..................................................................................................... 6 2  
1 0. 4 . 3 
C ollecti o n of pre g na nc y i nf or mati o n  ................................................................................. 6 3  
1 0. 5  A p pe n di x 5: Tec h nical c o m plai nts: Defi niti o n a n d pr oce d ures f or rec or di n g, e val uati o n, 
f oll o w-u p a n d re p orti n g  .................................................................................................................... 6 5  
1 0. 5. 1  
Defi niti o n of tec h nical c o m plai nt  ...................................................................................... 6 5  
1 0. 5. 2  
Rec or di n g a n d f oll o w -u p of tec h nical c o m plai nts  ............................................................. 6 5  
1 0. 5. 3  
Re p orti n g of tec h nical c o m plai nts  ..................................................................................... 6 6  
1 0. 6  A p pe n di x 6: Rete nti o n of h u ma n bi osa m ples  ................................................................................... 6 7  
1 0. 7  A p pe n di x 7: H y p o gl ycae mic e pis o des  .............................................................................................. 6 8  
1 0. 8  A p pe n di x 8: A b bre viati o ns  ............................................................................................................... 7 0  
1 1  Ref ere nces  .................................................................................................................................................. 7 2  
Pr ot oc ol attac h me nt I Gl o bal list of ke y staff a n d rele va nt de part me nts a n d s u p pliers  
Pr ot oc ol attac h me nt II C o u ntr y list of ke y staff a n d rele va nt de part me nts.  
 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5  of 7 4  
 
1  Pr ot oc ol s u m m ar y  
1. 1   
S y n o psis  
R ati o n ale:  
Wei g ht l oss is rec o m me n de d f or t y pe 2 dia betes ( T 2 D) ma na ge me nt, as it re d uces fat acc u m ulati o n 
i n li ver a n d pa ncreas, le a di n g t o i m pr o ve d i ns uli n secreti o n a n d i ns uli n se nsiti vit y. Wei g ht l oss i n 
patie nts wit h T 2 D wit h o ver wei g ht or o besit y is ass ociate d wit h a decrease i n H b A 1c. C o m bi ne d 
a d mi nistrati o n of t he l o n g -acti n g a m yli n a nal o g ue ca grili nti de a n d t he gl uca g o n -li ke pe pti de-1 
( G L P-1) rece pt or a g o nist se ma gl uti de was i n vesti gat e d i n a p hase 1 trial ( N N 9 8 3 8 -4 3 9 5) a n d 
ass ociate d wit h a s u bsta ntial wei g ht l oss c o m pare d t o se ma gl uti de al o n e i n i n di vi d uals wit h 
o ver wei g ht a n d o besit y wit h o ut T 2 D. Treat me nt wit h se ma gl uti de is well -esta blis he d i n T 2 D t o 
sec ure g o o d gl ycae mic c o ntr ol a n d is a p pr o ve d w orl d wi de u n der t his i n dicati o n. O ne s h ort -acti n g 
a m yli n a g o nist is c urre ntl y a p pr o ve d f or treat me nt of  t ype 1 dia betes ( T 1 D ) a n d T 2 D. A 
c o m bi nati o n of a l o n g -acti n g a m yli n a g o nist a n d s e ma gl uti de c o ul d lea d t o n ot o nl y s u bsta ntial 
wei g ht l oss b ut p ote ntiall y als o a n i m pr o ve d gl ycae mic c o ntr ol i n s u bjects wit h T 2 D. C o nse q ue ntl y, 
it is rele va nt t o i n vesti gat e w het her a greater i m pr o ve me nt i n gl ycae mic c o ntr ol as meas ure d b y a 
decrease i n H b A 1c is o bser ve d after c o m bi ne d a d mi nistrati o n of ca grili nti de a n d se ma gl uti de 
c o m pare d t o se m a gl uti de or ca grili nti de al o ne.  
O bjecti ves a n d e n d p oi nts:  
Pri m ar y o bjecti ves  
T o c o m pare t h e effect of c o -a d mi nistere d s e ma gl uti de a n d ca grili nti de vers us se ma gl uti de i n 
s u bjects wit h T 2 D i na de q uatel y c o ntr olle d o n metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or o n:  
•  c ha n ge fr o m baseli ne ( wee k 0) t o wee k 3 2 i n H b A 1c ( %-p oi nt)  
Sec o n d ar y o bjecti ves  
T o c o m pare t h e effect of c o -a d mi nistere d s e ma gl ut i de a n d ca grili nti de vers us se ma gl uti de i n 
s u bjects wit h T 2 D i na de q uatel y c o ntr olle d o n metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or o n:  
•  ot her para meters f or gl ycae mic c o ntr ol  
•  b o d y wei g ht  
T o c o m pare t h e effect of c o -a d mi nistere d s e ma gl uti de a n d ca grili nti de v ers us ca grili nti de i n 
s u bjects wit h T 2 D i na de q uatel y c o ntr olle d o n metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or o n:  
•  H b A 1c 
•  ot her para meters f or gl ycae mic c o ntr ol  
•  b o d y wei g ht  
T o c o m pare t h e effect of c o -a d mi nistere d s e ma gl uti de a n d ca grili nti de, se m a gl uti de a n d  ca grili nti de 
i n s u bjects wit h T 2 D i na de q uatel y c o ntr olle d o n metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or o n: 
•  safet y a n d t olera bilit y 
•  h y p o gl ycae mia  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
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V V- T M F- 4 5 3 5 0 0 0
7 4
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6  of 7 4  
 
Pri m ar y e n d p oi nt  
E n d p oi nt title  
Ti me fr a me  
U nit  
C ha n ge i n H b A 1c  
Fr o m baseli ne ( wee k 0) t o we e k 3 2  
% -p oi nt  
Pri m ar y esti m a n d  
T he pri mar y esti ma n d a d dresses t he mai n q uesti o n of i nterest: W hat is t he effect of c o -a d mi nistere d 
se ma gl uti de a n d ca grili nti de vers us se ma gl uti de o n H b A 1c ( %-p oi nts) fr o m baseli ne t o wee k 3 2 i n 
s u bjects wit h T 2 D i na de q uatel y c o ntr olle d on metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or, ha d all 
s u bjects re mai ne d o n tri al treat me nt wit h o ut use of resc u e me dicati o n (a nti -dia betic). A h y p ot h etical 
strate g y is a p plie d f or b ot h i nterc urre nt e ve nt of pre mat ure treat me nt disc o nti n uati o n a n d i nitiati o n  
of resc u e me dicati o n. T h e p o p ulati o n le vel s u m mar y is differe nce i n mea ns.  
T he pri mar y esti ma n d esti mates t he ac hie va ble treat me nt effect wit h o ut t he c o nf o u n di n g of 
treat me nt disc o nti n uati o n a n d i nitiati o n of resc ue i nter ve nti o n. T his a p pr oac h is c o nsi dere d rele va nt 
f or e val u ati n g a mec ha nistic effect.  
O ver all desi g n:  
T his is a 3 2 -wee k, ra n d o mise d, d o u ble -bli n d, acti ve -c o ntr olle d, t hree -ar m, parallel gr o u p, 
m ultice ntre cli nical trial. T he trial will c o m pare t h e effi cac y a n d safet y of c o -a d mi nistrati o n of 
ca grili nti de s u bc uta ne us (s.c.) 2. 4 m g a n d se m a gl uti de s.c. 2. 4 m g vers us s e ma gl uti de s.c. 2. 4 m g 
m o n ot hera p y a n d vers us ca grili nti de s.c. 2. 4 m g m o n ot hera p y i n s u bjects wit h T 2 D.  
S u bjects will be ra n d o mise d t o 1 of t he 3 treat me nt ar ms i n a rati o of 1: 1: 1 .  
Ra n d o misati o n will be stratifie d acc or di n g t o t he S G L T 2 i n hi bit or treat me nt ( Yes/ N o).  
Ke y i ncl usi o n criteri a:  
•  F e male of n o n -c hil d beari n g p ote ntial  or mal e  
•  A ge a b o ve or e q u al t o 1 8 years at t he ti me of si g ni n g i nf or m e d c o nse nt  
•  B o d y mass i n de x ( B MI) ≥ 2 7. 0 k g/ m 2 
•  Dia g n os e d wit h t y p e 2 dia betes mellit us ≥ 1 8 0 da ys bef ore s cree ni n g  
•  H b A 1c of 7. 5 -1 0. 0 % ( 5 8 -8 6 m m ol/ m ol) ( b ot h i ncl usi ve) as assess e d b y ce ntral la b orat or y at 
scree ni n g 
•  Sta ble dail y d ose(s) ≥ 9 0 da ys b ef ore scree ni n g of t he f oll o wi n g a nti dia betic  dr u g(s) or 
c o m bi nati o n re gi me n(s) at ma xi m u m t olerate d or effecti ve d ose as j u d ge d b y t he 
i n vesti gat or: metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or 
Ke y e xcl usi o n criteri a:  
•  Treat me nt wit h a n y me di cati o n f or t he i n dicati o n of dia betes or o b esit y ot h er t ha n state d i n 
t he i ncl usi o n criteria wit hi n 9 0 da ys b ef ore scree ni n g. H o we ver, s h ort ter m i ns uli n treat me nt 
f or a ma xi m u m of 1 4 da ys a n d pri or i ns uli n treat me nt f or gestati o nal dia b etes are all o we d 
•  Re nal i m pair me nt wit h esti mate d Gl o mer ular Filtrati o n Rate (e G F R) < 6 0 ml/ mi n/ 1. 7 3 m 2 b y 
ce ntral la b orat or y at scree ni n g  
•  U nc o ntr olle d a n d p ote nti all y u nsta ble dia b etic reti n o pat h y or mac ul o pat h y. Verifie d b y a 
f u n d us e x a mi nati o n perf or me d wit hi n 9 0 da ys b ef ore scree ni n g or i n t he peri o d bet wee n 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
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V V- T M F- 4 5 3 5 0 0 0
7 4
 of
6
 
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7  of 7 4  
 
scree ni n g a n d ra n d o misati o n. P har mac ol o gi cal p u pil-dilati o n is a re q uire me nt u nless usi n g a 
di gital f u n d us p h ot o gra p h y ca mera s pecifi e d f or n o n -dilate d e x a mi nati o n  
N u m ber of s u bjects:  
A p pr o xi matel y 9 0 s u bj ects will be ra n d o ml y assi g ne d t o trial pr o d uct.   
Tre at me nt gr o u ps a n d d ur ati o n:  
T he trial i ncl u des a mi ni m u m 1 0 -da y s cree ni n g p eri o d t o assess t he s u bject’s eli gi bilit y, a 3 2 -wee k 
treat me nt peri o d a n d a 5-wee k f oll o w u p peri o d. T he 3 2 -wee k treat me nt peri o d c o nsists of a 
1 6 -wee k d os e escalati o n peri o d a n d a 1 6 -wee k mai nte na nce p eri o d. T he pla n ne d t otal trial d urati o n 
f or t he i n di vi d ual s u bject is a p pr o xi matel y 3 9 wee ks. 
T he f oll o wi n g tri al pr o d u cts will be s u p plie d b y N o v o N or dis k A/ S f or t he d urati o n of t he trial:  
•  Se ma gl uti de B 3. 0 m g/ m L P D S 2 9 0  pre -fille d pe n -i nject or a n d se ma gl uti de place b o, s ol uti o n 
f or i njecti o n, 3 m L P D S 2 9 0 pre-fille d pe n-i nject or 
•  Ca grili nti de A 1 0 m g/ m L a n d ca grili nti de place b o, s ol uti o n f or i njecti o n, 3 m L u n der -fille d 
cartri d ge, 1 ml s ol uti o n f or i njecti o n t o be use d wit h N o v o Pe n Ec h o ®  
D at a m o nit ori n g c o m m ittee:  
N ot a p plica ble f or t his st u d y . 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
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V V- T M F- 4 5 3 5 0 0 0
7 4
 of
7
 
-
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0  of 7 4  
 
2  
I ntr o d ucti o n 
Dia betes mellit us is a meta b olic dis or der c h aracterise d b y t he prese n ce of h y p er gl ycae mia d ue t o 
defecti ve i ns uli n secreti o n, i ns uli n acti o n or b ot h. C hr o nic h y p er gl ycae mia of dia betes mellit us is 
ass ociate d wit h si g nifica nt l o n g -ter m c o m plicati o ns, partic ularl y da ma ge, d ysf u ncti o n a n d fail ure of 
vari o us tiss ues  –  es peciall y t he ki d ne y, e ye a n d n er ves. 1 Dia betes is ge nerall y classifie d acc or di n g 
t o aeti ol o gical fact ors, w here T 1 D a n d T 2 D c o nstit ute t he vast maj orit y of cases. I n t he 
I nter nati o nal Dia betes Fe derati o n’s Dia betes Atlas ( 2 0 1 9), t he esti mate d w orl d wi de dia betes 
pre vale nce was 4 6 3 milli o n, wit h a pre dicti o n t hat b y 2 0 4 5, t he n u m ber of pe o ple wit h dia betes will 
ha ve i ncrease d t o 7 0 0 milli o n. 2 
T he p ur p ose of t h e pres e nt trial is t o i n vesti gate t he effi cac y a n d safet y of t he c o m bi nati o n of t he 
G L P -1 rece pt or a g o nist  ( G L P-1 R A) , s e ma gl uti de a n d a m yli n a nal o g ue, ca grili nti de (i nter nati o nal 
n o n pr o prietar y n a me), b ot h a d mi nistere d o nce  wee kl y.  
G L P -1 is a n i n creti n h or m o ne releas e d fr o m i ntesti nal L -cells wit h a gl uc ose -de pe n d e nt sti m ulat or y 
effect o n i ns uli n a n d i n hi bit or y effect o n gl u ca g o n secreti o n fr o m t he pa ncreatic islets. 3 G L P -1 is a 
p h ysi ol o gical r e g ulat or of a p petite a n d G L P -1 rece pt ors are prese nt  i n se veral areas of t he brai n 
i n v ol ve d i n a p petite re g ulati o n.4 Treat me nt wit h G L P -1 rece pt or a g o nists l o wers b o d y wei g ht a n d 
re d uces H b A1c.4 Se ma gl uti de s.c. is a o nce -wee kl y G L P -1 r ece pt or a g o nist a p pr o ve d f or t he 
treat me nt of a d ults wit h T 2 D at d oses of 0. 5 a n d 1. 0 m g ( Oze m pic
® ). O n ce-wee kl y s e ma gl uti de s.c. 
has rece ntl y b ee n s u b mitte d f or re g ulat or y re vie w at d ose of 2. 0 m g f or a d diti o nal gl ycae mic c o ntr ol 
f or a d ults wit h T 2 D, a n d at d ose of 2. 4 m g f or wei g ht ma na ge me nt i n a d ults.  
E n d o ge n o us a m yli n is a ne ur oe n d ocri ne pe pti de h or m o ne t hat is c o -secrete d wit h i ns uli n fr o m 
pa ncreatic beta -cells i n r es p o nse t o f o o d i nta ke. St u dies i n dicate t hat e n d o ge n o us a m yli n is i n v ol ve d 
i n t he ce ntral r e g ulati o n of f o o d i nta ke a n d b o d y wei g ht. 5 Pra mli nti de ( S y mli n ® ) is a s h ort-acti n g 
am yli n a n al o g u e w hic h was a p pr o ve d i n 2 0 0 5 i n t he U nite d States ( U S) as a mealti me a dj u nct 
treat me nt t o i ns uli n i n patie nts wit h T 1 D a n d T 2 D t o c o ntr ol bl o o d gl uc ose.6 Pra mli nti de has bee n 
s h o w n t o sl o w gastric e m pt yi n g a n d t o s u p press p ost-pra n dial gl uca g o n release. 7 Ca grili nti de is a 
l o n g-acti n g a m yli n a nal o g ue wit h a g o nistic effects o n a m yli n rece pt ors. T he wei g ht l oss p ote ntial of 
ca grili nti de has bee n i n ve sti gate d i n a p hase 2 tri al a n d t he c o m bi nati o n wit h se ma gl uti de has bee n 
i n vesti gate d i n a p h ase 1 trial. T he res ults c ollecti v el y i n dicate d t hat t he c o m bi nati o n has t he 
p ote ntial t o offer s u bsta ntiall y greater wei g ht l oss t ha n eit her m o n ot hera p y.  
2. 1   
Tri al r ati o n ale  
Wei g ht l oss is rec o m me n de d i n cli nical practice g ui deli nes f or T 2 D ma n a ge me nt,
8, 9 as it re d uces 
fat acc u m ulati o n i n li ver a n d pa ncreas, lea di n g t o i m pr o ve d i ns uli n secreti o n a n d i ns uli n 
se nsiti vit y. 1 0 Wei g ht l oss i n patie nts wit h T 2 D wit h o ver wei g ht or o besit y is ass ociate d wit h a 
decrease i n H b A 1c.1 1  
Base d o n t h e wei g ht -l o w eri n g effect of c o m bi ni n g ca grili nti de a n d se ma gl uti de, t he esta blish e d 
effect of se ma gl uti de o n gl ycae mic c o ntr ol as well as t he p ote ntial i n v ol ve me nt of a m yli n a g o nists 
i n gl uc ose met a b olis m, it is rele va nt t o i n vesti gate w het her a greater i m pr o ve me nt i n gl ycae mic 
c o ntr ol as meas ure d b y a decrease i n H b A 1c is o bser ve d after c o m bi ne d a d mi nistrati o n of 
ca grili n ti de a n d se ma gl uti de c o m pare d t o s e ma gl uti de or ca grili nti de al o ne.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
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V V- T M F- 4 5 3 5 0 0 0
7 4
 of
1 0
 
-
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 1  of 7 4  
 
2. 2   
B ac k gr o u n d  
Se m a gl uti de  
Se ma gl uti de s.c. is a o n ce -wee kl y G L P -1 rece pt or a g o nist a p pr o ve d f or t he treat me nt of a d ults wit h 
T 2 D at d oses of 0. 5 a n d 1. 0  m g ( Oze m pic ® ). O n ce-wee kl y s e ma gl uti d e s.c. has rece ntl y b ee n 
s u b mitte d f or re g ulat or y re vie w at d os e of 2. 0 m g f or a d diti o nal gl ycae mic c o ntr ol f or a d ults wit h 
T 2 D, a n d at d ose of 2. 4 m g f or wei g ht ma na ge me nt. Se ma gl uti de has a half -life of a p pr o xi matel y 
1 6 0 h o urs, ma ki n g it s uita ble f or o n c e-wee kl y d osi n g. 1 2  
I n t he p hase 3 d e vel o p me nt pr o gra m me f or s e ma gl uti de s.c. 0. 5 a n d 1. 0 m g (t he S U S T AI N 
pr o gra m me), se ma gl uti de pr o vi de d s u peri or l o n g -ter m gl ycae mic c o ntr ol a n d b o d y wei g ht 
re d ucti o n as c o m p are d t o c o m m o nl y use d mar kete d pr o d ucts acr oss t he s pectr u m of patie nts wit h 
T 2 D, ra n gi n g fr o m treat me nt -naï ve t o i ns uli n -treate d. T he safet y pr ofile of se ma gl uti de is well-
d oc u me nte d base d o n d at a fr o m  t he n o ncli nical a n d cli nical de vel o p me nt pr o gra m mes, a n d is 
c o nsiste nt wit h t he safet y pr ofile of ot her dr u gs wit hi n t he G L P -1 R A dr u g class. 1 3, 1 4  
T he S U S T AI N F O R T E trial ( N N 9 5 3 5 -4 5 0 6) i ncl u de d 9 6 1 pe o ple wit h T 2 D. I n t he trial, pe o ple 
treate d wit h se ma gl uti de 2. 0 m g ac hie ve d a s u peri or re d ucti o n i n H b A1c c o m pare d t o se ma gl uti de 
1. 0 m g. B ot h d oses of se ma gl uti de a p p eare d t o ha ve safe a n d well -t olerate d pr ofiles. T he m ost 
c o m m o n a d verse e ve nts were gastr oi ntesti nal, t he vast maj orit y were mil d t o m o derate a n d 
di mi nis he d o ver ti me a n d were c o nsiste nt wit h t he G L P -1 rece pt or a g o nist class. C o m pare d t o 
se ma gl uti de 1. 0 m g, t he gastr oi ntesti nal a d verse e ve nts were si milar f or se ma gl uti de 2. 0 m g.
1 5 
A gl o bal p h ase 3a cli nical de vel o p me nt pr o gra m m e wit h se ma gl uti de s.c. 2. 4 m g o nce  wee kl y h as 
bee n c o m plete d i n p e o ple wit h o ver wei g ht or o besit y ( S T E P pr o gra m me). T he lar gest trial 
( N N 9 5 3 6-4 3 7 3; S T E P 1) i ncl u de d 1, 9 6 1 a d ults wit h o besit y or o ver wei g ht wit h c o m or bi dities. 
S u bjects treate d wit h se ma gl uti de s.c. 2. 4 m g o n ce  wee kl y ac hi e ve d si g nifica ntl y greater wei g ht 
l oss ( 1 4. 9 %) after 6 8 wee ks c o m pare d t o place b o ( 2. 4 %), b ot h i n c o nj u ncti o n wit h lifest yle 
i nter ve nti o n.1 6 I n a trial wit h 1, 2 1 0 a d ults wit h B MI ≥2 7 k g/ m2 a n d T 2 D ( N N 9 5 3 6 -4 3 7 4; S T E P 2) a 
si g nifica ntl y greater wei g ht l oss was ac hie ve d wit h se ma gl uti de s.c. 2. 4 m g o nce  wee kl y ( 9. 6 %) vs . 
se ma gl uti de s. c. 1. 0 m g ( 7. 0 %) a n d vs. place b o ( 3. 4 %); all i n c o nj u ncti o n wit h lifest yl e 
i nter ve nti o n.1 7 T he safet y pr of ile of se ma gl uti de s.c. 2. 4 m g o n ce wee kl y was c o nsiste nt wit h t hat 
see n pre vi o usl y wit h se m a gl uti de o nce wee kl y i n t y p e 2 di a betes, 1 8 a n d wit h t he esta blis he d pr ofile 
of t he G L P -1 rece pt or a g o nist class. 1 9, 2 0 T he m ost c o m m o n a d verse e ve nts a m o n g p e o ple treate d 
wit h se ma gl uti de 2. 4 m g o nce  wee kl y were gastr oi ntesti nal e ve nts. 1 6, 1 7 
A c o m pre he nsi v e re vie w of res ults fr o m t he n o ncli nical a n d cli nical st u dies of se ma gl uti de s.c. 
2. 4  m g o nce  wee kl y ca n be f o u n d i n t he c urre nt e diti o n of t he i n vesti gat or’s br oc h ure (I B)
2 1 a n d a n y 
u p dates here of.  
C a grili nti de  
Ca grili nti de is a l o n g -acti n g a m yli n a g o nist u n der i n vesti gati o n f or t he treat me nt of s u bjects wit h 
o ver wei g ht a n d o besit y, as well as s u bjects wit h T 2 D. T he half -life of ca grili nti de  is a p pr o xi matel y 
1 8 0 h o urs i n dicati ve of a p har mac o ki netics ( P K) pr ofile s uita ble f or a o nce -wee kl y d osi n g re gi me n.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
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V V- T M F- 4 5 3 5 0 0 0
7 4
 of
1 1
 
-
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 2  of 7 4  
 
A p hase 2 d ose -fi n di n g trial has bee n c o m plet e d f or ca grili nti de ( N N 9 8 3 8-4 4 3 3). T he 2 6 -wee k 
bli n de d p hase 2 m o n ot hera p y trial wit h ca grili nti de s.c. i n vesti gate d safet y, t olera bilit y a n d efficac y 
f or wei g ht ma na ge me nt i n 7 0 6 a d ults wit h o besit y or o ver wei g ht wit h at least o ne wei g ht-relate d 
c o m or bi dit y. T he s u bjects were ra n d o mise d e q u all y t o o nce -wee kl y treat me nt wit h fi ve differe nt 
d oses o f ca grili nti de s.c. ( 0. 3 m g, 0. 6 m g, 1. 2 m g, 2. 4 m g, 4. 5 m g), place b o o nce  wee kl y or 
lira gl uti de 3. 0 m g o nce d ail y, i n c o nj u ncti o n wit h lifest yle i nter v e nti o n. Base d o n t he pri mar y 
e n d p oi nt, t he wei g ht l oss o bser ve d f or all ca grili nti de d oses was si g nifica ntl y greater  t h a n f or 
place b o. Fr o m a bas eli ne wei g ht of a p pr o xi matel y 1 0 0 k g, treat me nt wit h 2. 4 m g a n d 4. 5 m g s.c. 
ca grili nti de res ulte d i n a wei g ht l oss of 9. 7 % a n d 1 0. 8 % at wee k 2 6, res p ecti vel y, c o m pare d t o a 
wei g ht l oss of 3. 0 % wit h place b o. Ca grili n ti de ha d a safe a n d well-t olerate d pr ofile wit h t he m ost 
fre q ue ntl y re p orte d a d verse e ve nts bei n g gastr oi nt esti nal ( n o n-seri o us a n d mil d t o m o derate i n 
se verit y) a n d i njecti o n site reacti o ns (all n o n-seri o us a n d mil d t o m o derate i n se verit y). 
A c o m pre he nsi v e re vie w of res ults fr o m t he n o ncli nical a n d cli nical st u dies of ca grili nti de ca n be 
f o u n d i n t he c urre nt e diti o n of t he I B2 2 a n d a n y u p dates here of.  
C o m bi n ati o n tri al  
Res ults are a vaila bl e fr o m a m ulti ple -asce n di n g d ose trial i n vesti gati n g t he saf et y, t olera bilit y a n d 
P K pr o perties of 6 ca grili nti de d oses ( 0. 1 6 m g u p t o 4. 5 m g per wee k) a d mi nistere d i n c o m bi nati o n 
wit h t he sa me se ma gl uti de d ose ( 2. 4 m g per wee k) as se parate s.c. i njecti o ns ( N N 9 8 3 8 -4 3 9 5). A 
2 0 -wee k tr eat me nt peri o d was a p plie d i ncl u di n g a  1 6 -wee k d os e -es calati o n peri o d f oll o we d b y 
4  wee ks at t he tar get d os e. T he res ults de m o nstrate d t hat ca grili nti de was well -t olerate d i n 
c o m bi nati o n wit h se ma gl uti de 2. 4 m g wit h t he m ost fre q ue nt a d verse e ve nts relate d t o 
gastr oi ntesti nal i nt olera n ce a n d i njecti o n site reacti o ns. N o ne w safet y c o ncer ns were i de ntifie d f or 
t he c o m bi nati o n c o m pare d t o t he safet y pr ofile of t he m o n o-c o m p o ne nts. After 2 0 wee ks of 
treat me nt, s u bjects r ecei vi n g 2. 4 m g ca grili nti de i n c o m bi nati o n wit h 2. 4 m g se ma gl uti de l ost a n 
a vera ge of 1 7. 1 % of b o d y wei g ht w hile a wei g ht l oss of 9. 8 % was o bser ve d f or se ma gl uti de 2. 4 m g 
m o n ot hera p y. He n ce, a n a d diti o nal wei g ht l oss was o bser ve d w he n c o m bi ni n g 2. 4 m g ca grili nti de 
a n d 2. 4 m g s e ma gl uti de treat me nt.  
A c o m pre he nsi v e re v ie w of res ults fr o m t he n o ncli nical a n d cli nical st u dies of ca grili nti de i n 
c o m bi nati o n wit h se ma gl uti de ca n be f o u n d i n t he c urre nt e diti o n of t he ca grili nti de I B 2 2 a n d a n y 
u p dates here of.  
2. 3   
Be nefit -ris k assess me nt  
Mai n be nefits a n d ris ks are descri b e d i n t he bel o w secti o ns. M ore detaile d i nf or mati o n a b o ut t he 
k n o w n a n d e x pecte d be n efits a n d ris ks a n d reas o n a bl y e x pecte d a d verse e v e nts of ca grili nti de or 
se ma gl uti de ma y b e f o u n d i n t he I Bs 2 1, 2 2 a n d a n y u p dates t here of.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
1 2
 
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 4  of 7 4  
 
Acti vati o n of t he 
R e ni n -A n gi ote nsi n -
Al d oster o n  S yste m  
ca grili nti de  
Treat me nt wit h ca grili nti de has bee n 
ass ociate d wit h i ncrease d mea n le vels of 
al d oster o ne a n d re ni n, wit hi n n or mal 
ra n ge. N o sti m ulat or y effect o n bl o o d 
press ure, heart rate or c ha n ges i n 
electr ol ytes has bee n o bser ve d. 2 1 
Plas ma re ni n acti vit y, al d oster o ne le vels, 
electr ol ytes a n d bl o o d press ure will be 
m o nit o re d ( A p pe n di x 2, Secti o n 1 0. 2 ). 
De vel o p me nt of a nti -
ca grili nti de 
a nti b o dies  
ca grili nti de  
Ca grili nti de has a hi g h h o m ol o g y t o nati ve 
a m yli n. I n t he p hase 2 trial ( N N 9 8 3 8 -
4 4 3 3), u p t o 7 3 % of s u bj ects de vel o pe d 
a nti -ca grili nti de a nti b o dies i n a d ose -
de pe n de nt ma n ner. A n i ncrease d ris k of 
i nj ecti o n site reacti o ns was o bser ve d i n 
s u bj ects wit h a nti b o dies. 
N o miti gati n g acti o ns are i m pl e me nte d. 
Sa m pli n g f o r i n vesti gati o n of prese nce of 
a nti b o dies (a nti -ca grili nti de I g E a n d a nti -
se ma gl uti de I g E) will be perf or me d i n case of 
s yste mic h y perse nsiti vit y reacti o ns (see 
S ecti o n 8. 3. 7 ). 
Ac ute pa ncreatitis  
se ma gl uti de 
Ac ute pa ncreatitis has bee n o bser ve d wit h 
t he use of G L P-1 R As .2 1, 2 2   
T he fre q ue nc y of a dj u dicati o n -c o nfir me d 
ac ute pa ncreatitis re p orte d i n S T E P 
cli nical de vel o p me n t pr o gra m me was 
0. 2 % f or se ma gl uti de 2. 4 m g a n d < 0. 1 % 
f or place b o, res pecti vel y. O verall, 
se ma gl uti de was n ot ass ociate d wit h a n 
i ncrease d ris k of ac ute pa ncreatitis vs 
c o m parat or.  
S u bj ects wit h a hist or y of c hr o nic or rece nt 
ac ute pa ncreatitis will n ot be e nr olle d (see 
Secti o n 5. 2 ).  
S u bj ects s h o ul d be i nf or me d of t he 
c haracteristic s y m pt o ms of ac ute pa ncreatitis 
a n d if pa ncreatitis is s us pecte d, trial pr o d uct 
s h o ul d be disc o nti n ue d. If c o nfir me d, trial 
pr o d uct s h o ul d n ot be restarte d i n acc or da nce 
wit h Secti o n 7 . 
M T C ( base d o n n o n -
cli nical data)  
se ma gl uti de 
T h yr oi d C -cell t u m o urs ha ve bee n 
o bser ve d i n carci n o ge nicit y st u dies of 
se ma gl uti de i n r o de nts, b ut n ot i n 
m o n ke ys. T he r o de nt C-cell t u m o urs are 
ca use d b y a n o n -ge n ot o xic, s p ecific G L P -1 
rece pt or-me diate d mec ha nis m t o w hic h 
r o de nts are partic ularl y se nsiti ve. T he 
G L P -1 rece pt or is n ot e x presse d i n t he 
n or mal h u ma n t h yr oi d, a n d t heref ore t he 
cli nical rele va nce of t he fi n di n gs is 
c o nsi dere d t o be l o w.2 2  
S u bj ects wit h a fa mil y or pers o nal hist or y of 
m ulti ple e n d ocri ne ne o plasia t y pe 2 ( M E N 2) 
or me d ullar y t h yr oi d ca ncer will be e xcl u de d 
fr o m t he trial (see Secti o n 5. 2 ). 
 
Ne o plas ms 
( mali g na nt a n d n o n-
mali g na nt)  
se ma gl uti de 
P atie nts wit h o ver wei g ht or o besit y as well 
as patie nts wit h T 2 D, ha ve a n i ncrease d 
ris k of certai n t y pes of ca ncer. T here is n o 
e vi de nce fr o m cli nical st u dies t hat G L P -1 -
base d t hera pies i ncrease t he ris k of 
ne o plas ms. N o i m bala nce was o bser ve d i n 
t he se ma gl uti de 2. 4 m g f or wei g ht 
ma na ge me nt p hase 3a trials wit h re gar ds t o 
t he pr o p orti o ns of s u bj ects wit h ne o plas ms 
( mali g na nt a n d n on -mali g na nt). H o we ver, 
i n t he se ma gl uti de s.c. as well as oral 
se ma gl uti de p hase 3a st u dies f or T 2 D, t he 
pr o p orti o n of s u bj ects wit h ne o plas ms 
( mali g na nt a n d n o n-mali g na nt) were 
sli g htl y hi g her wit h se ma gl uti de t ha n wit h 
c o m parat or. T he n u m ber of s u bj ects 
e x p ose d t o se ma gl uti de s.c. or oral 
se ma gl uti de f or a l o n ger peri o d is 
c o nsi dere d i ns ufficie nt f or a t h or o u g h 
assess me nt of t he ris k of ne o plas ms.  
S u bj ects wit h a hist or y of mali g na nt 
ne o plas ms wit hi n t he past 5 years pri or t o 
scree ni n g will n ot be e nr olled i n t his trial. 
Basal a n d s q ua m o us cell s ki n ca ncer a n d a n y 
carci n o ma i n -sit u is all o we d (see Secti o n 5. 2 ). 
 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
1 4
 
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 7  of 7 4  
 
3. 1. 2   
Sec o n d ar y o bjecti ves  
T o c o m pare t h e effect of c o -a d mi nistere d s e ma gl uti de a n d ca grili nti de vers us se m a gl uti de i n 
s u bjects wit h T 2 D i na de q uatel y c o ntr olle d o n metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or o n:  
•  ot her para meters f or gl ycae mic c o ntr ol  
•  b o d y wei g ht  
T o c o m pare t h e effect of c o -a d mi nistere d s e ma gl uti de a n d ca grili nti de vers us ca grili nti de i n 
s u bjects wit h T 2 D i na de q uatel y c o ntr olle d o n metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or o n:  
•  H b A 1c  
•  ot her para meters f or gl ycae mic c o ntr ol  
•  b o d y wei g ht  
T o c o m pare t h e effect of c o -a d mi nistere d s e ma gl uti de a n d ca grili nti de, se m a gl uti de a n d ca grili nti de 
i n s u bjects wit h T 2 D i na de q uatel y c o ntr olle d o n metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or o n:  
•  safet y a n d t olera bilit y 
•  h y p o gl ycae mia  
3. 1. 3   
Esti m a n ds  
A pri mar y a n d a n a d diti o nal esti ma n d is defi ne d f or t he pri mar y o bjecti ve. T w o i nterc urre nt e ve nts 
are i de ntifie d: treat me nt disc o nti n uati o n a n d i nitiati o n of a nti-dia betic res c ue i nter ve nti o n. T he 
attri b utes f or t he esti ma n ds are s u m marise d i n Ta ble  3 -1 . 
Pri m ar y esti m a n d  
T he pri mar y esti ma n d a d dresses t he mai n q uesti o n of i nterest: W hat is t he effect of c o -a d mi nistere d 
se ma gl uti de a n d ca grili nti de vers us se ma gl uti de o n c ha n ge i n H b A 1c ( %-p oi nts) fr o m baseli ne t o 
wee k 3 2 i n s u bjects wit h T 2 D i na de q uatel y c o ntr olle d o n m etf or mi n wit h or wit h o ut S G L T 2 
i n hi bit or, ha d all s u bjects re mai ne d o n trial treat m e nt wit h o ut use of resc u e me dicati o n (a nti-
dia betic). A h y p ot hetical strate g y is a p plie d f or b ot h i nterc urre nt e ve nt of pre mat ure treat me nt 
disc o nti n uati o n a n d i nitiati o n of  resc ue me di cati o n. T he p o p ulati o n le vel s u m mar y is differe n ce i n 
mea ns.  
T he pri mar y esti ma n d esti mates t he ac hie va ble treat me nt effect wit h o ut t he c o nf o u n di n g of 
treat me nt disc o nti n uati o n a n d i nitiati o n of resc ue i nter ve nti o n. T his a p pr oac h is c o nsi dere d rele va nt 
f or e val u ati n g a mec ha nistic effect.  
A d diti o n al esti m a n d f or t he pri m a r y o bjecti ve  
T he a d diti o nal esti ma n d a d dresses a differe nt q uesti o n of i nterest: W hat is t he effect of  
c o-a d mi nistere d s e ma gl uti de a n d ca grili nti de vers us se ma gl uti de o n H b A 1c ( %-p oi nts) fr o m 
baseli ne t o wee k 3 2 i n s u bjects wit h T 2 D i na de q u atel y c o ntr olle d wit h metf or mi n wit h or wit h o ut 
S G L T 2 i n hi bit or, re gar dl ess of pre mat ure treat me nt disc o nti n uati o n or i nitiati o n of resc u e 
me dicati o n (a nti -dia betic).  
F or t he a d diti o nal esti m a n d, t he treat me nt p olic y strate g y is a p plie d f or b ot h t he i nterc urre nt e ve nt 
of i nitiati o n of pre mat ure treat me nt disc o nti n uati o n or resc u e me dicati o n. T he p o p ulati o n -le vel 
s u m mar y is differe n ce i n mea ns. Res ults base d o n t he a d diti o nal esti ma n d are e x pec te d t o mirr or t he 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
1 7
 
-
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 8  of 7 4  
 
cli nical practice sce n ari o beca use t h e esti ma n d c o nsi ders b ot h t he efficac y a n d t olera bilit y of 
treat me nts. 
T a ble  3 -1  Attri b utes f or t he esti m a n ds  
Esti m a n d 
c ate g or y 
Tre at me nt c o n diti o n   
V ari a ble/
E n d p oi nt  
P o p ul ati o n 
of i nterest  
I nterc urre nt e ve nt 
str ate g y 
P o p ul ati o n -le vel 
s u m m ar y me as ure 
Pri mar y   
T he effect of c o -
a d mi nistere d se ma gl uti de 
a n d ca grili nti de vers us 
se ma gl uti de o n H b A 1c, 
b ot h as a d d -o n t o 
metf or mi n wit h or wit h o ut 
S G L T 2 i n hi bit or a n d 
wit h o ut resc ue me dicati o n  
C ha n ge i n 
H b A 1c 
( %-p oi nt) 
fr o m 
baseli ne t o 
wee k 3 2  
S u bj ects 
wit h T 2 D 
i na de q uatel y 
c o ntr olle d o n 
metf or mi n 
wit h or 
wit h o ut 
S G L T 2 
i n hi bit or 
H y p ot hetical 
strate g y f or 
•
 I nitiati o n of a n y 
resc ue me dicati o n 
• 
Treat me nt 
disc o nti n uati o n  
Differe nce i n 
mea ns  
A d diti o nal   
T he effect of c o -
a d mi nistere d se ma gl uti de 
a n d ca grili nti de vers us 
se ma gl uti de o n H b A 1c, 
b ot h as a d d -o n t o 
metf or mi n wit h or wit h o ut 
S G L T 2 i n hi bit or  
Treat me nt p olic y 
strate g y f or 
•
 I nitiati o n of a n y 
resc ue me dicati o n  
•
Treat me nt 
disc o nti n uati o n  
3. 2   
Pri m ar y, sec o n d ar y a n d e x pl or at or y e n d p oi nt(s)  
3. 2. 1   
Pri m ar y e n d p oi nt  
E n d p oi nt title  
Ti me fr a me  
U nit  
C ha n ge i n H b A 1c  
Fr o m baseli ne ( wee k 0) t o we e k 3 2  
% -p oi nt  
3. 2. 2   
Sec o n d ar y e n d p oi nts  
3. 2. 2. 1   
C o nfir m at or y s ec o n d ar y e n d p oi nts  
N ot a p plica ble f or t his trial.  
3. 2. 2. 2   
S u p p orti ve sec o n d ar y e n d p oi nts  
E n d p oi nt title  
Ti me fr a me  
U nit  
C ha n ge i n fasti n g plas ma gl uc ose ( F P G)   
Fr o m baseli ne ( wee k 0) t o we e k 3 2  
m m ol/ L a n d m g/ d L  
C G M: C ha n ge i n mea n gl uc os e  
Fr o m baseli ne ( wee k 0) t o we e k 3 2  
m m ol/ L a n d m g/ d L  
C G M: T i me a b o ve ra n ge ( T A R) > 1 0. 0 
m m ol/ L  ( > 1 8 0 m g/ d L) 
At wee k 3 2  
% of rea di n gs  
C G M: T i me i n ra n ge ( TI R) 3. 9 – 1 0. 0 
m m ol/ L  ( 7 0– 1 8 0 m g/ d L)  
At wee k 3 2  
% of rea di n gs  
C ha n ge i n b o d y wei g ht  
Fr o m baseli ne ( wee k 0) t o we e k 3 2  
%  
C ha n ge i n b o d y wei g ht  
Fr o m baseli ne ( wee k 0) t o we e k 3 2  
K g  
N u m ber of treat me nt e mer ge nt a d verse 
e ve nts ( T E A Es)  
Fr o m baseli ne ( wee k 0) t o we e k 3 7  
C o u nt  
N u m ber of cli nicall y si g nifica nt 
h y p o gl ycae mic e pis o des (le vel 2) 
( < 3. 0 m m ol/ L ( 5 4 m g/ d L), c o nfir me d b y 
B G meter) or se vere h y p o gl yc ae mic 
e pis o des (le vel 3)  
Fr o m baseli ne ( wee k 0) t o we e k 3 7   
C o u nt of e pis o des  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
1 8
 
-
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 9  of 7 4  
 
4  
Tri al desi g n  
4. 1   
O ver all desi g n  
T his is a 3 2 -wee k, ra n d o mise d, d o u ble -bli n d, acti ve -c o ntr olle d, t hree -ar m, parallel gr o u p, 
m ultice ntre cli nical trial. T he trial will c o m pare t h e  effi cac y a n d safet y of c o -a d mi nistrati o n of 
ca grili nti de s.c. 2. 4 m g o nce  wee kl y a n d se ma gl uti de s.c. 2. 4 m g o n ce  wee kl y vers us s e ma gl uti de 
s.c. 2. 4 m g o n ce wee kl y m o n ot hera p y vers us ca grili nti de s.c. 2. 4 m g o nce  wee kl y m o n ot hera p y i n 
s u bjects wit h T 2 D.  
A p pr o xi matel y 9 0 eli gi bl e s u bjects will be ra n d o mise d t o 1 of t he 3 treat me nt ar ms i n a rati o of 
1: 1: 1. Ra n d o misati o n will be stratifie d acc or di n g t o t he S G L T 2 i n hi bit or treat me nt ( Yes/ N o).  
T he trial i ncl u des a mi ni m u m 1 0 -da y s cree ni n g p eri o d t o assess s u bject eli gi bilit y, a 3 2 -wee k 
treat me nt peri o d a n d a 5-wee k f oll o w u p peri o d. T he 3 2 -wee k treat me nt peri o d c o nsists of a 
1 6 -wee k d os e escalati o n peri o d a n d a 1 6 -wee k mai nte na nce p eri o d. T he pla n ne d t otal trial d urati o n 
f or t he i n di vi d ual s u bject is a p pr o xi matel y 3 9 wee ks.  
T o e val uate t he effect o n gl ycae mic c o ntr ol, s u bjects will ha ve C G M pr ofiles c ollecte d, as s pecifi e d 
i n t he fl o wc hart (s ee Secti o n 1. 2 ). T his will i ncl u de C G M pr ofili n g d uri n g t he 1 0-da y scree ni n g 
peri o d re prese nti n g baseli ne C G M e val uati o n. T he C G M will be bli n de d f or b ot h s u bjects a n d 
i n vesti gat ors a n d n ot us e d f or d ose a dj ust me nts. 
T he trial desi g n is ill ustrate d i n Fi g ure  4 -1 . 
Fi g ure  4 -1  
Sc he m atic di a gr a m of t he tri al desi g n  
 
4. 2   
Scie ntific r ati o n ale f or tri al desi g n  
A ra n d o mise d, d o u ble -bli n de d trial desi g n h as bee n c h ose n t o i ncrease t he vali dit y of t he trial a n d t o 
a v oi d bias. Ca grili nti de s.c. 2. 4 m g o n ce  wee kl y a n d se ma gl uti de s.c. 2. 4 m g o nce  wee kl y are 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
1 9
 
-
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2 0  of 7 4  
 
c h ose n as acti ve c o m parat ors. T he pri mar y o bjecti ve is t o c o m pare t he effect of c o -a d mi nistrati o n 
of ca grili nti de  s.c. 2. 4 m g o nce  wee kl y a n d se ma gl uti de s.c. 2. 4 m g o nce  wee kl y vers us s e ma gl uti de 
s.c. 2. 4 m g o n ce wee kl y o n gl ycae mic c o ntr ol. B ot h efficac y a n d safet y of c o -a d mi nistrati o n of 
ca grili nti de s.c. 2. 4 m g o nce  wee kl y a n d se ma gl uti de s.c. 2. 4 m g o n ce  wee kl y c o m pare d t o eac h 
i n di vi d ual c o m p o ne nt will be i n vesti gate d. Se ma gl uti de is k n o w n t o ha ve a gl uc ose l o weri n g effect 
a n d is a p pr o ve d f or treat me nt of T 2 D i n l o wer d oses t ha n i n vesti gat e d i n t his trial. N o cli nical data 
o n t he effect of treat me nt wit h ca grili nti de o n gl ycae mic c o ntr ol i n s u bjects wit h T 2 D are c urre ntl y 
a vaila ble a n d t heref ore a ca grili nti de s.c. 2. 4 m g o nce  wee kl y treat me nt ar m has bee n i ncl u de d i n 
t his trial. 
T he pla n ne d tr eat me nt d urati o n is 3 2 wee ks. T he treat me nt d urati o n i ncl u d es a 1 6 -wee k d ose 
escalati o n peri o d a n d a 1 6 -wee k mai nte na nce peri o d. T he d ose of trial pr o d uct will be escalat e d 
e ver y 4 wee ks t o miti gat e t he ris ks of gastr oi ntesti nal si de effects. T he t otal treat me nt d urati o n of 3 2 
wee ks is e x pecte d t o e ns ure a de q u ate ti me f or c o m pari n g t he effect o n H b A
1c i n acc or da nce wit h 
t he pri mar y o bjecti ve of t he trial. A 1 0-da y s cree ni n g peri o d is i ncl u de d t o e ns ure eli gi bilit y of 
s u bjects a n d t o c ollect C G M pr ofiles bef ore t he i nitiati o n of treat me nt wit h trial pr o d uct s. 
F urt her m ore, a 1 0 -da y C G M data c ollecti o n will be c o n d ucte d after t he d ose escal ati o n peri o d a n d 
at t he e n d of t he mai nte n a nce p eri o d. A f oll o w -u p visit is pla n ne d t o c ollect data o n safet y 5 wee ks 
after e n d of treat me nt t o acc o u nt f or t he l o n g half -life of trial pr o d ucts. 
T he ra n d o misati o n rati o is 1: 1: 1 t o e ns ure a bala nce d c o m paris o n bet w ee n gr o u ps. T o a v oi d a 
pr o n o u nce d differe nce i n S G L T 2 i n hi bit or use bet wee n t he treat me nt ar ms at baseli ne, 
ra n d o misati o n will be stratifie d acc or di n g t o t he S G L T 2 i n hi bit or treat me nt ( Yes/ N o).  
T he relati vel y h o m o ge n e o us trial p o p ulati o n of s u bjects wit h T 2 D w h o are i n i na de q uate gl ycae mic 
c o ntr ol usi n g metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or ha ve bee n c h ose n t o li mit t he varia bilit y. 
I n cl u di n g s u bjects wit h H b A1c of 7. 5 % -1 0. 0 % all o w s f or a n e val uati o n of gl uc ose p ara meters. O nl y 
s u bjects wit h B MI ≥ 2 7. 0 k g/ m 2 are i ncl u de d t o miti gate t he n ee d f or re d u cti o n i n d ose i n case t he 
c o-a d mi nistrati o n of ca grili nti de a n d se ma gl uti de l ea ds t o pr o n o u nce d wei g ht re d ucti o n i n s u bjects 
wit h T 2 D.  
4. 3   
J ustific ati o n f or d ose  
Se ma gl uti de s.c. h as bee n a p pr o ve d f or treat me nt of T 2 D i n t he d oses of 0. 5 m g a n d 1. 0 m g a n d a 
d ose of 2. 0 m g is c urre ntl y u n der re g ul at or y re vi e w. Wit hi n t he wei g ht ma na ge me nt i n dicati o n, a 
gl o bal p has e 3a cli nical de vel o p me nt pr o g ra m me wit h se ma gl uti de s.c. 2. 4 m g o nce wee kl y is u n der 
re g ulat or y re vie w. O ne of t he trials c o m plete d wit hi n t he p hase 3a wei g ht ma na ge me nt pr o gra m me 
( N N 9 5 3 6-4 3 7 4) i n cl u de d 1 2 1 0 s u bjects wit h o ver wei g ht or o besit y a n d T 2 D. Se ma gl uti de s.c. 
2. 4  m g o nce  wee kl y a p peare d t o ha ve a safe a n d well t olerate d pr ofile i n li n e wit h w hat has 
pre vi o usl y b ee n o bser ve d f or se ma gl uti de 2 3. 
Base d o n t h e res ults fr o m cli nical trials (see Secti o n  2. 1 ) a ca grili nti de d ose of 2. 4 m g a d mi nistere d 
i n c o m bi nati o n wit h se ma gl uti de s.c. 2. 4 m g is c o nsi dere d t o pr o vi de ma xi m u m effect o n b o d y 
wei g ht w hile e ns uri n g safet y a n d t olera bilit y. T he o nce wee kl y c o m bi nati o n of ca grili nti de 2. 4 m g 
a n d se ma gl uti de 2. 4 m g is bei n g i n vesti gate d wit hi n t he i n dicati o n of wei g ht ma na ge me nt. Si nce 
wei g ht l oss is ass ociate d wit h i m pr o ve me nts i n gl ycae mic p ara met ers (see Secti o n 2. 1 ) d oses of 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
2 0
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2 1  of 7 4  
 
2. 4  m g f or b ot h ca grili nti de a n d se ma gl uti de will be use d t o i n vesti gate w h et her ca grili nti de a d ds t o 
t he gl uc os e l o weri n g effect of se ma gl uti de i n s u bjects wit h T 2 D. 
Escalat i o n of t he ca grili nti de a n d se ma gl uti de d oses will be d o ne e ver y 4 wee ks, u ntil t he 
mai nte na nce d os e is reac he d after 1 6 wee ks, i n or der t o miti gate t he well -k n o w n gastr oi ntesti nal 
si de effects o bser ve d wit h b ot h ca grili nti de a n d se ma gl uti de treat me nts.  
4. 4   
E n d of tri al defi niti o n  
A s u bject is c o nsi dere d t o ha ve c o m plete d t h e trial if he/s he has c o m plete d all p hases of t he trial 
i ncl u di n g t he last visit s h o w n i n t he fl o wc hart.  
T he e n d of t he tri al is defi ne d as t he date of t he last visit of t he last s u bject i n t he trial. 
5  
Tri al p o p ul ati o n  
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr ol me nt criteria, als o k n o w n as 
pr ot oc ol wai vers or e x e m pti o ns, is n ot per mitte d.  
5. 1   
I ncl usi o n criteri a 
S u bjects are eli gi ble t o b e i ncl u de d i n t he trial o nl y if all of t he f oll o wi n g criteria a p pl y:  
1.  I nf or me d c o ns e nt o btai ne d bef ore a n y trial-relate d acti vities. Trial-rel ate d acti vities are a n y 
pr oce d ures t hat are carrie d o ut as part of t he trial, i ncl u di n g acti vities t o deter mi ne s uita bilit y f or 
t he trial 
2.  F e male of  n o n -c hil d beari n g p ote ntial (s ee defi niti o n i n A p pe n di x 4, Secti o n 1 0. 4 ) or male  
3.  A ge a b o ve or e q u al t o 1 8 years at t he ti me of si g ni n g i nf or m e d c o nse nt  
4.  B MI ≥ 2 7. 0 k g/ m 2 
5.  Dia g n os e d wit h t y p e 2 dia betes mellit us ≥ 1 8 0 da ys bef ore s cree ni n g  
6.  H b A 1c of 7. 5 -1 0. 0 % ( 5 8 -8 6 m m ol/ m ol) ( b ot h i ncl usi ve) as assess e d b y ce ntral la b orat or y at 
scree ni n g 
7.  Sta ble dail y d ose(s) ≥ 9 0 da ys b ef ore scree ni n g of t he f oll o wi n g a nti dia betic dr u g(s) or 
c o m bi nati o n re gi me n(s) at ma xi m u m t olerate d or effecti ve d ose as j u d ge d b y t he i n vesti gat or: 
metf or mi n wit h or wit h o ut S G L T 2 i n hi bit or  
8.  A ble a n d willi n g t o a d here t o t he pr ot oc ol i ncl u di n g weari n g pr o visi o ne d c o nti n u o us gl uc ose 
m o nit ori n g ( C G M) de vice base d o n t he I n vesti gat or’s j u d ge me nt  
5. 2   
E xcl usi o n criteri a   
S u bjects are e x cl u de d fr o m t he trial if a n y of t he f oll o wi n g criteria a p pl y:  
1.  Treat me nt wit h a n y me di cati o n f or t he i n dicati o n of dia betes or o b esit y ot h er t ha n state d i n t he 
i ncl usi o n criteria wit hi n 9 0 da ys b ef ore scree ni n g. H o we ver, s h ort ter m i ns uli n treat me nt f or a 
ma xi m u m of 1 4 da ys a n d pri or i ns uli n treat me nt  f or gestati o nal dia betes are all o we d 
2.  Pre vi o us or pla n ne d ( d uri n g t he trial p eri o d) o besit y treat me nt wit h s ur ger y o r a wei g ht l oss 
de vice. H o we ver, t h e f oll o wi n g are all o we d: ( 1) li p os ucti o n a n d/ or a b d o mi n o plast y, if 
perf or me d > 1 year bef ore scree ni n g, ( 2) la p ba n di n g, if t he b a n d has bee n re m o ve d > 1 year 
bef ore s cree ni n g, ( 3) i ntr a gastric ball o o n, if t he b all o o n has  bee n re m o v e d > 1 year bef ore 
scree ni n g or ( 4) d u o d e nal-je n u nal b y p ass slee v e, if t he slee ve h as bee n re m o ve d > 1 year bef ore 
scree ni n g 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
2 1
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2 2  of 7 4  
 
3.  A ntici pate d i nitiati o n or c ha n ge i n c o nc o mita nt me dicati o ns (f or m ore t ha n 1 4 c o nsec uti ve da ys) 
k n o w n t o affect wei g ht or gl uc os e meta b olis m (e. g. treat me nt wit h orlistat, t h yr oi d h or m o nes, or 
c ortic oster oi ds)  
4.  Prese nce or hist or y of c hr o nic pa ncreatitis a 
5.  Prese nce or hist or y of ac ute pa ncreatitis wit hi n 1 8 0 da ys b ef ore scree ni n g a 
6.  M y ocar dial i nfarcti o n, str o ke, h os pitalizati o n f or u nsta ble a n gi na pect oris or tra nsie nt isc hae mic 
attac k wit hi n 1 8 0 da ys bef ore scree ni n g  
7.  C hr o nic heart fail ure cl assifie d as bei n g i n Ne w Y or k Heart Ass ociati o n ( N Y H A) Class I V at 
scree ni n g 
8.  Pla n ne d c or o nar y, car oti d or peri p heral art er y re v asc ularisa ti o n 
9.  Pers o nal or first -d e gree relati ve(s) hist or y of m ulti ple e n d ocri ne n e o plasia t y p e 2 or me d ullar y 
t h yr oi d carci n o maa 
1 0.  Re nal i m pair me nt wit h esti mate d Gl o mer ular Filtrati o n Rate (e G F R) < 6 0 ml/ mi n/ 1. 7 3 m 2 b y 
ce ntral la b orat or y at scree ni n g  
1 1.  I m paire d li ver f u ncti o n, defi ne d as Al a ni ne A mi n otra nsferase ( A L T) ≥ 2. 5 ti mes or Bilir u bi n 
> 1. 5 ti mes u p per n or mal li mit ( U N L) b y ce ntral la b orat or y at scree ni n g  
1 2.  Hist or y or prese n ce of a disease, ca usi n g i m paire d calci u m h o me ostasis as j u d ge d b y t he 
i n vesti gat or 
1 3.  U nc o ntr olle d a n d p ote nti all y u nsta ble dia b etic reti n o pat h y or mac ul o pat h y. Verifie d b y a f u n d us 
e x a mi nati o n perf or me d wit hi n 9 0 da ys bef ore s cree ni n g or i n t he peri o d bet wee n scree ni n g a n d 
ra n d o misati o n. P har mac ol o gical p u pil-dilati o n is a re q uire me nt u nless usi n g a di gital f u n d us 
p h ot o gra p h y ca mera s pecifie d f or n o n -dilate d e x a mi nati o n  
1 4.  A n y e pis o des a of dia betic ket oaci d osis wit hi n 9 0 da ys b ef ore scree ni n g  
1 5.  Rec urre nt s e vere h y p o gl ycae mic e pis o des wit hi n t he last year as j u d ge d b y t he I n v esti gat or  
1 6.  I n a de q uat el y treate d bl o o d press ure d efi ne d as S yst olic ≥1 8 0 m m H g or diast olic ≥1 1 0 m m H g at 
scree ni n g 
1 7.  Prese nce or hist or y of mali g na nt ne o plas m ( ot h er t ha n basal or s q u a m o us cell s ki n ca ncer, i n -
sit u carci n o mas of t he cer vi x, or i n sit u pr ostate ca ncer) wit hi n 5 years bef or e scree ni n g  
1 8.  S ur ger y sc he d ul e d f or t h e d urati o n of t he trial, e x pect f or mi n or s ur gical pr oce d ures, i n t he 
o pi ni o n of t he I n v esti gat or  
1 9.  Use of a n y me di cati o n wit h u n k n o w n or u ns pecifi e d c o nte nt wit hi n 9 0 da ys bef ore s cree ni n g.  
2 0.  K n o w n or s us pect e d h y p erse nsiti vit y t o trial pr o d uct(s) or relate d pr o d u cts  
2 1.  Pre vi o us partici pati o n i n t his trial. Partici pati o n is defi ne d as si g ne d i nf or me d c o nse nt  
2 2.  Fe male w h o is pre g na nt, breast-fee di n g or i nte n ds t o bec o me pre g n a nt or is of c hil d beari n g 
p ote ntial  
2 3.  Partici pati o n i n a n y cli nical trial of a n a p pr o ve d or n o n -a p pr o ve d i n vesti gati o nal me dici nal 
pr o d uct wit hi n 9 0 da ys b ef ore s cree ni n g  
2 4.  A n y dis or d er, w hic h i n t he i n vesti gat or’s o pi ni o n  mi g ht je o par dise s u bject’s safet y or 
c o m plia nce wit h t he pr ot oc ol  
a: As declare d b y t he s u bj ect or i n t he me dical rec or ds  
5. 3   
Lif est yle c o nsi der ati o ns  
T o e ns ure ali g n me nt re gar di n g perf or m a nce of ass ess me nts acr oss s u bjects a n d trial sites, t he bel o w 
restricti o ns a p pl y. 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
2 2
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2 6  of 7 4  
 
A u xili ar y s u p plies  
A u xiliar y s u p plies will b e pr o vi de d i n acc or da nce wit h t he trial materials ma n ual ( T M M) a n d 
Ta ble  6 -4 . 
T a ble  6 -4   
A u xili ar y s u p plies  
A u xili ar y s u p pl y  
Det ails  
Nee dles  
O nl y nee dles pr o vi de d a n d a p pr o ve d b y N o v o N or dis k m ust be use d f or 
a d mi nistrati o n of trial pr o d uct.  
Bl o o d gl uc ose ( B G) meter   
S u bj ects m ust be i nstr ucte d i n h o w t o use t he B G meter as s p ecifie d i n A p pe n di x 7, 
Secti o n 1 0. 7 . Please refer t o t he ma n ufact urer’s g ui de. 
C o nti n u o us  gl uc ose  
m o nit ori n g ( C G M)  
S u bj ects m ust be i nstr ucte d i n ha n dli n g of t he C G M as s pecifie d i n t he fl o wc hart , 
Secti o n 1. 2 . Please refer t o t he C G M S u bj ect G ui de pr o vi de d. 
Directi o n  f or use ( D F U)  
D F U f or P D S 2 9 0 pre -fille d pe n-i nj ect or a n d N o v o P e n Ec h o ®  
N ot i ncl u de d i n t he dis pe nsi n g u nit a n d t o be ha n de d o ut se p aratel y  
 
T he B G m eter pr o vi d e d b y N o v o N or dis k s h o ul d be use d if t he s u bject e x perie nces a 
h y p o gl ycae mic e pis o de , see A p pe n di x 7 ( Secti o n 1 0. 7 ). 
Trai ni n g i n t he p e n -i nject or a n d d ura bl e de vice is t he res p o nsi bilit y of t he i n vesti gat or or a del e gate 
a n d m ust be re peate d d uri n g t he trial at re g ular i nt er vals, as s pecifie d i n t he fl o wc hart 
(see Secti o n  1. 2 ) i n or d er t o e ns ure c orrect use of t he pe n-i nject or.  
6. 1. 1   
Me dic al de vices  
I nf or mati o n a b o ut t he P D S 2 9 0 pre-fille d pe n-i nject or f or s e ma gl uti de/ place b o a n d N o v o Pe n Ec h o ®  
d ura ble de vice f or ca grili nti de/ place b o ca n be f o u n d i n t he D F U.  
6. 2   
Pre p ar ati o n/ h a n dli n g/st or a ge/ acc o u nt a bilit y  
O nl y s u bjects ra n d o mise d t o treat me nt ma y use trial pr o d uct a n d o nl y dele gat e d site staff ma y 
s u p pl y trial pr o d uct. 
•  Eac h site will be s u p plie d wit h s ufficie nt trial pr o d ucts f or t he trial o n a n o n g oi n g basis. 
Trial pr o d ucts will be distri b ute d t o t he sites acc or di n g t o scree ni n g a n d ra n d o misati o n.  
•  T he i n vesti gat or or desi g nee m ust c o nfir m t hat a p pr o priate te m perat ure c o n diti o ns ha ve 
bee n mai ntai ne d d uri n g tra nsit f or all trial pr o d ucts recei v e d, a n d t hat a n y discre pa n cies are 
re p orte d a n d res ol ve d b ef ore use of t he trial pr o d ucts. 
•  All trial pr o d ucts m ust be st ore d i n a sec ure, c o ntr olle d, a n d m o nit ore d ( ma n ual or 
a ut o mate d) area i n acc or da nce wit h t he la belle d st ora ge c o n diti o ns wit h access li mite d t o t he 
i n vesti gat or a n d dele gate d site staff. 
•  T he i n vesti gat or m ust i nf or m N o v o N or dis k i m me diatel y if a n y trial pr o d uct has bee n st ore d 
o utsi de s pecifie d c o n diti o ns. T he trial pr o d uct m ust n ot be dis pe nse d t o a n y s u bject b ef ore it 
has bee n e v al uate d a n d a p pr o ve d f or f urt her us e b y N o v o N or dis k. A d diti o nal details 
re gar di n g h a n dli n g of t e m perat ure d e viati o ns ca n be f o u n d i n t he trial mat erials ma n ual 
( T M M). 
•  T he i n v esti gat or or desi g nee is res p o nsi ble f or dr u g acc o u nta bilit y a n d rec or d mai nte na nce 
(i.e. recei pt, acc o u nta bilit y a n d fi nal dis p ositi o n rec or ds). 
•  T he i n vesti gat or or desi g nee m ust i nstr uct t he s u bject i n w hat t o ret ur n at ne xt visit.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
2 6
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2 7  of 7 4  
 
•  Dr u g acc o u nta bilit y s h o ul d be perf or me d at pe n le vel.  
•  Destr ucti o n of trial pr o d u cts ca n be p erf or me d o n a n o n g oi n g b asis a n d will be d o ne 
acc or di n g t o l ocal pr oce d ures after acc o u nta bilit y is fi nalise d b y t he site a n d rec o ncile d b y 
t he m o nit or. 
•  All ret ur ne d, u n -us e d , e x pire d or da ma ge d trial pr o d ucts (f or tec h nical c o m plai nt sa m ples, 
see Secti o n 1 0. 5 ) m ust be st ore d se paratel y fr o m n o n-all ocate d trial pr o d ucts. N o 
te m perature m o nit ori n g is re q uire d.  
•  N o n -all ocate d trial pr o d u cts i ncl u di n g e x pire d or da ma ge d pr o d u cts m ust be acc o u nte d as 
u n use d, at t he latest at cl os ure of t he site.  
6. 2. 1   
S hi p me nt of tri al pr o d uct t o s u bject’s h o me  
If per mitte d b y l ocal re g ulati o ns, t he i n vesti gat or ma y offer t o s e n d trial pr o d ucts a n d a u xiliaries 
fr o m t he trial site or p har mac y t o t he s u bject’s h o me b y c o urier ser vice.  
T he pr ocess f or se n di n g trial pr o d uct fr o m t he tri al site or p har mac y t o a s u bject’s h o me is 
descri be d i n t he “ Trial site/ p har mac y  i nstr ucti o n f or s hi p me nt of trial pr o d uct t o s u bjects’ h o mes” 
d oc u me nt. T his d oc u me nt c o ntai ns detaile d i nstr ucti o ns f or pre p ari n g pac k a gi n g a n d setti n g u p t he 
pic k -u p of trial pr o d u ct s, ha n d o ver of tri al pr o d ucts fr o m t he trial site or p h ar mac y staff t o t he 
c o urier, re q uire d t e m perat ure m o nit ori n g of tri al pr o d uct s, deli ver y t o a n d recei pt of trial pr o d u cst 
b y t he s u bject. T he pr ocess f or ret ur ni n g trial pr o d uct t o t he trial site or p har mac y b y c o urier is als o 
des cri be d i n t his d oc u me nt.  
I n v esti gat ors, trial site staff a n d s u bjects w h o will be i n v ol ve d i n s hi p me nt of trial pr o d uct t o t he 
s u bject’s h o me will be a d e q uatel y trai ne d i n t his pr ocess. 
6. 3   
Me as ures t o mi ni mise bi as: R a n d o mis ati o n a n d bli n di n g  
All s u bjects will be ce ntr all y scree n e d a n d ra n d o mise d usi n g a n I W R S a n d assi g ne d t o t he n e xt 
a vaila ble treat me nt acc or di n g t o ra n d o misati o n sc he d ule. Trial pr o d ucts  will be dis pe nse d/all ocate d 
at t he trial visits s u m marise d i n t he fl o wc hart.  
Ra n d o misati o n  will be stratifie d acc or di n g t o treat me nt wit h S G L T 2 i n hi bit or at scree ni n g ( yes/ n o).  
At scree ni n g, eac h s u bject will be assi g ne d a u ni q ue 6 -di git S u bjects I D, w hic h will re mai n t he 
sa me t hr o u g h o ut t he trial. Eac h site is assi g n e d a 3-di git n u m ber a n d S u b ject I Ds start wit h t he site 
n u m ber.  
T he I W R S is use d f or bli n d -brea ki n g. I n cas e of a n e mer ge n c y, t he i n vesti gat or has t he s ole 
res p o nsi bilit y f or det er mi ni n g if u n bli n di n g of a s u bjects’ treat me nt is warra nte d. S u bject safet y 
m ust al wa ys b e t he first c o n si derati o n i n ma ki n g s uc h a deter mi nati o n. If t he i n vesti gat or deci d es 
t hat u n bli n di n g is warra nte d, t he i n vesti gat or s h o ul d ma ke e ver y eff ort t o c o ntact N o v o N or dis k 
pri or t o u n bli n di n g a s u bj ects’ treat me nt u nless t his c o ul d dela y e mer ge nc y treat me nt of t he s u bject. 
If a s u bject’s treat me nt is u n bli n de d, N o v o N or dis k ( Gl o bal Safet y de p art m e nt) m ust be n otifie d 
wit hi n 2 4 h o urs after brea ki n g t he bli n d. T he d ate a n d reas o n t h at t he bli n d was br o ke n m ust be 
rec or de d i n t he me dical rec or ds. T he p ers o n brea ki ng t he bli n d m ust pri nt t he “c o d e brea k 
c o nfir mati o n” n otificati o n ge n erat e d b y t he I W R S, si g n a n d d ate t he d oc u m e nt. If I W R S is n ot 
accessi ble at t he ti me of bli n d brea k, t he I W R S hel p des k s h o ul d be c o ntact e d. C o ntact details are 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
2 7
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2 9  of 7 4  
 
•  will n ot be pr o vi de d b y N o v o N or dis k u nless re q uire d b y l o cal la w a n d s h o ul d be p urc has e d 
or ot her wise d eli vere d t o s u bjects i n acc o r da nce wit h l ocal healt h pla ns  
•  S h o ul d be use d i n acc or da nce wit h sta n dar d of care or l ocal la b el i n t he c o u ntr y  
I n v esti gat ors ca n s witc h oral a nti -dia betic ( O A D ) treat me nt wit hi n t he sa me dr u g c lass, e. g. i n case 
s pecific dr u gs b ec o me u na vaila ble. C ha n ges  i n c o nc o mita nt me dicati o n, i ncl u di n g s witc h of O A D 
treat me nt wit hi n t he sa me dr u g class m ust be rec or de d at eac h visit / p h o ne c o ntact. If a c ha n ge is 
d ue t o a n  A E,  t he n t his m ust be re p orte d acc or di n g t o Secti o n 8. 3 . 
6. 5. 1   
Resc ue me dic ati o n  
Gl ycae mic resc u e me dicati o n, i.e. i nte nsificati o n of bac k gr o u n d oral a nti -dia betic ( O A D) 
me dicati o n a n d/ or i nitiati o n of ne w a nti -dia betic me dicati o n, s h o ul d be i m ple me nte d at t he 
discreti o n of t he i n vesti gat or i n case of persiste nt h y per gl ycae mia. Please s ee Secti o n 7. 1. 2 . 
Resc ue me dicati o n s h o ul d be selecte d acc or di n g t o t he A D A/ E A S D g ui deli ne 2 4, 2 5 (e x cl u di n g 
G L P -1 R As, di pe pti d yl p e pti dase -4 ( D P P -4) i n hi bit ors a n d a m yli n a n al o g u es).  
S u bjects t hat are start e d o n resc ue m e dicati o n s h o ul d c o nti n ue t o f oll o w t he pr ot oc ol -s pecifie d visit 
sc he d ule a n d sta y o n ra n d o mise d treat me nt u nless t he i n vesti gat or j u d ge t hat it je o par dises s u bject’s 
safet y. 
Resc ue me dicati o n (i nte nsificati o n of e xisti n g bac k gr o u n d m e dicati o n a n d/ or i nitiati o n of ne w 
me dicati o n)  a n d a n y c ha n ges t o t his s h o ul d be d oc u me nte d i n me dical rec or ds a n d re p orte d o n t he 
c onc o mita nt me dicati o n f or m i n t he e C R F.  
Resc ue me dicati o n will n ot be s u p plie d b y N o v o N or dis k.  
6. 6   
D ose m o dific ati o n  
C o nsi der dela yi n g d os e escalati o n or re d u ci n g t he d ose d uri n g d os e escalati o n if:  
•  T he c urre nt d ose is n ot t olerate d b y t he s u bject. T his s h o ul d  o nl y b e all o we d if t he s u bject 
w o ul d ot her wise disc o nti n ue trial pr o d uct s c o m pletel y a n d o nl y  if c o nsi dere d safe t o 
c o nti n ue o n a n y trial pr o d ucts d ose, as per i n vesti gat or’s discreti o n  
C o nsi der re d uci n g t he m ai nte na nce d ose if:  
•  T he mai nte na nce d ose is n ot t olerate d b y t he s u bject. T he s u bject ma y sta y at a l o wer d ose 
le vel b ut o nl y if t he s u bject w o ul d ot her wise disc o nti n ue trial pr o d ucts c o m pletel y a n d o nl y 
if c o nsi dere d s afe t o c o nti n ue o n a n y trial pr o d ucts d ose, as per i n vesti gat or’s discreti o n.  
•  T he  s u bject ac hie ves a B MI of < 2 2. 5 k g/ m 2 a n d c o nti n ues l osi n g wei g ht, p er i n vesti gat or’s 
discreti o n  
 
D ose m o dificati o ns m ust  be a p plie d t o b ot h trial pr o d ucts. I n cas e of de viati o ns fr o m t he pla n ne d 
d ose escal ati o n re gi me n, it is rec o m me n de d t hat t he s u bject  ma kes at least o ne atte m pt t o re -es calat e 
t o t he mai nte na nce d os e, as per t he i n vesti gat or’s discreti o n. It is rec o m me n de d t hat t he i n vesti gat or 
c o ns ults N o v o N or dis k i n case of persiste nt de viati o ns fr o m t he pla n ne d es calati o n re gi me n . 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
2 9
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 0  of 7 4  
 
6. 7   
Tre at me nt after e n d of tri al  
W he n disc o nti n ui n g trial pr o d uct s at t he ‘e n d -of -treat me nt’ visit, t he s u bject s h o ul d be tra nsferre d 
t o a s uita ble mar kete d pr o d uct at t he discreti o n of t he i n vesti gat or. C o nsi deri n g t he l o n g half-life of 
se ma gl uti de a n d ca grili nti de a n d t o a v oid o ver -e x p os ure t o G L P -1 R As a n d i nterfere nce wit h safet y 
data c ollecti o n, i nitiati n g G L P -1 R A , D P P -4i or a m yli n a nal o g u es s h o ul d be a v oi de d bet wee n t he 
e n d-of -tr eat me nt visit ( V 1 6) a n d t he e n d -of -trial visit ( V 1 7). 
7  
Disc o nti n u ati o n of tri al tre at me nt a n d s u bject 
disc o nti n u ati o n/ wit h dr a w al  
Treat me nt of a s u bject m a y b e disc o nti n ue d at a n y ti me d uri n g t he trial at t h e discreti o n of t he 
i n vesti gat or f or safet y, be ha vi o ural, c o m plia nce or a d mi nistrati ve reas o ns. 
7. 1   
Disc o nti n u ati o n of tri al tre at me nt  
Trial pr o d uct s ma y be dis c o nti n ue d at a n y ti me d uri n g t he trial at t he discreti o n of t he s u bject or at 
t he discreti o n of t he i n vesti gat or f or safet y, b e ha vi o ural, c o m plia nce or a d mi nistrati ve reas o ns. 
T he trial pr o d uct s m ust be disc o nti n ue d, if a n y of t he f oll o wi n g a p p lies f or t he s u bject: 
1.  Safet y c o ncer n as j u d ge d b y t he i n vesti gat or  
2.  S us pici o n of ac ute pa n creatitis  
3.  Pre g n a nc y  
4.  Si m ulta ne o us use of a n a p pr o ve d or n o n -a p pr o ve d i n vesti gati o nal me dici nal pr o d uct i n a n ot her 
cli nical trial  
S u bjects  meeti n g disc o nti n uati o n of tre at me nt crit eria n o. 1, 2  or  3  ca n res u me trial pr o d ucts if t he 
criteria is n o l o n ger m et.  
F or disc o nti n uati o n of treat me nt criteri o n n o. 2:  
If ac ut e pa ncreatitis is s us pecte d, a p pr o priate acti o ns s h o ul d be i nitiate d, i ncl u di n g l ocal 
meas ure me nt of a m yl ase a n d li pase see A p pe n di x 3 ( Secti o n 1 0. 3 ). 
S u bjects ca n res u me trial pr o d ucts if t he Atla nta criteri o n2 6 is n ot f ulfille d a n d t h us t he s us pici o n of 
ac ute pa n creatitis is n ot c o nfir me d. Trial pr o d u cts  ma y b e res u me d f or s u bj ects wit h a gallst o ne -
i n d uce d pa ncreatitis i n case of c h olec yst ecto m y.  
T he pri mar y reas o n f or disc o nti n uati o n of trial pr o d ucts m ust be s pecifie d i n t he s u bject’s me dical 
rec or ds a n d t he e n d-of -tr eat me nt f or m i n t he e C R F, a n d fi nal dr u g acc o u nt a bilit y m ust be 
perf or me d. A ‘treat me nt stat us sessi o n’ m ust be ma de i n t he I W R S t o disc o nti n ue trial pr o d uct s. 
If a s u bject h as disc o nti n ue d trial pr o d ucts, eff orts m ust be ma de t o ha ve s u bjects atte n d a n d 
c o m plete all re mai ni n g s c he d ule d visit pr oce d ures. All eff orts s h o ul d be ma de t o ha ve t he s u bject 
atte n d at least visit V 1 2 , t he ‘e n d of  tr eat me nt’ visit ( V 1 6) a n d t he ‘e n d of  trial’ visit ( V 1 7).  If t he 
s u bjects d o n ot wis h t o atte n d t he sc he d ule d cli nic visits, eff orts s h o ul d be ma de t o ha ve t he 
re mai ni n g cli nic visits c o n verte d t o p h o ne call visits. If a s u bject is u n willi n g t o atte n d t he 
re mai ni n g visits, i nf or mati o n a b o ut t he atte m pts t o f oll o w u p wit h t he s u bject m ust be d oc u me nte d 
i n t he s u bject’s me dical r ec or ds . 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 0
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 1  of 7 4  
 
T he ‘e n d of  trial’ visit ( V 1 7) is sc he d ule d a p pr o xi matel y 5 wee ks after e n d of treat me nt t o e ns ure 
t he safet y of t he s u bj ect. If t he s u bject has disc o nti n ue d trial pr o d ucts > 5 wee ks pri or t o t he ‘e n d of  
treat me nt’ visit  ( V 1 6), a n d t he re q uire m e nts f or t h e f oll o w-u p peri o d pri or t o t he ‘e n d of  trial’ visit 
( V 1 7) are f ulfille d, t he n t he ‘e n d of  tri al’ visit  ( V 1 7) ca n be o mitte d.  
7. 1. 1   
Te m p or a r y disc o nti n u ati o n of tri al tre at me nt  
If a s u bject h as disc o nti n ue d trial pr o d ucts d ue t o te m p orar y safet y c o n cer n n ot relate d t o trial 
pr o d ucts a n d ca n res u me treat me nt, t he s u bject s h o ul d f oll o w t he g ui de f or misse d d oses Ta ble  6 -3 . 
Si milarl y, a s u bject w h o disc o nti n ues trial pr o d uct s o n t heir o w n i nitiati ve s h o ul d be e nc o ura ge d t o 
res u me trial pr o d u cts ( Secti o n 6. 1 ). A ‘treat me nt stat us sessi o n’ m ust be ma de i n t he I W R S w he n a 
s u bject pa uses treat me nt or res u mes treat me nt. 
I n case of s us pici o n of ac ute pa ncreatitis, t he trial pr o d ucts m ust pr o m ptl y be di sc o nti n ue d; 
h o we ver, ‘treat me nt stat us sessi o n’ s h o ul d n ot be ma de i n I W R S bef ore dia g n osis of ac ute 
pa ncreatitis is c o nfir me d. If ac ut e pa ncreatitis is c o nfir me d, treat me nt wit h trial pr o d uct s m ust n ot 
be restart e d, a n d a ‘treat me nt stat us sessi o n’ s h o ul d  be ma de i n I W R S.  
7. 1. 2   
Resc ue criteri a  
If a n y of t he F P G val u es e x cee d t he li mits o utli ne d bel o w a n d n o i nterc urre nt ca use of t he 
h y per gl ycae mia ca n b e i de ntifie d, t he s u bject s h o ul d be offere d resc ue me dicati o n, see 
Secti o n  6. 5. 1 ). 
Resc ue me dicati o n s h o ul d be offere d if F P G val ues e x cee ds:  
•  
1 5. 0 m m ol/ L ( 2 7 0 m g/ d L) fr o m ra n d o misati o n t o e n d of wee k 8  
•  
1 3. 3 m m ol/ L ( 2 4 0 m g/ d L) fr o m wee k 9 t o e n d of wee k 2 0  
•  
1 1. 1 m m ol/ L ( 2 0 0 m g/ d L) fr o m wee k 2 1 t o e n d of treat me nt  
A c o nfir mat or y F P G s h o ul d be o btai ne d b y t he ce ntral la b orat or y. If t he c o nfir mat or y F P G e x cee ds 
t he val ues descri be d a b o ve, t he s u bject s h o ul d be offere d res c ue me dicati o n at t he discreti o n of t he 
i n vesti gat or a n d in acc or da nce wit h t he A D A/ E A S D g ui deli ne 2 4, 2 7 (e x cl u di n g G L P-1 R As, D P P -4 
i n hi bit ors a n d a m yli n a nal o g ues). R esc ue me di cati o n s h o ul d be prescri be d as a d d-o n t o ra n d o mise d 
treat me nt a n d s u bjects s h o ul d c o nti n ue t o f oll o w t he pr ot oc ol -s pecifie d visit sc he d ule. 
7. 2   
S u bject wit h dr a w al f r o m t he tri al  
A s u bject ma y wit h dra w c o nse nt at a n y ti me at his/ her o w n re q u est  
If a s u bject wit h dra ws c o nse nt, t he i n vesti gat or m ust as k t he s u bject if he/s he is willi n g, as s o o n as 
p ossi ble, t o ha ve assess m e nt perf or m e d acc or di n g t o  ‘e n d of treat me nt ’ visit ( V 1 6). See t he 
fl o wc hart ( Secti o n 1. 2 ) f or data t o be c ollecte d. 
Fi nal dr u g acc o u nta bilit y m ust be perf or me d e ve n if t he s u bject is n ot a ble t o c o me t o t he site. A 
‘treat me nt status  sessi o n’ m ust be ma de i n t he I W R S.  
If t he s u bject wit h dra ws c o nse nt, N o v o N or dis k ma y retai n a n d c o nti n ue t o use a n y data c ollecte d 
bef ore  s u c h a wit h dr a wal of c o nse nt. 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 1
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 2  of 7 4  
 
If a s u bject wit h dra ws fr o m t he trial, he/s he ma y re q uest destr ucti o n of a n y sa m ples ta ke n a n d n ot 
teste d, a n d t he i n vesti gat or m ust d oc u me nt t his i n t he me dical rec or d. 
Alt h o u g h a s u bject is n ot o bli ge d t o gi ve his/ her reas o n(s) f or wit h dra wi n g, t he i n vesti gat or m ust 
ma ke a reas o na bl e eff ort t o ascertai n t he reas o n(s), w hile f ull y res pecti n g t h e s u bject’s ri g hts. 
W here t he reas o ns are o btai ne d, t he pri mar y reas o n f or wit h dra wal m ust be s pecifie d i n t he e n d of 
trial f or m i n t he e C R F. 
7. 2. 1   
Re pl ace me nt of s u bjects  
S u bjects w h o disc o nti n ue trial pr o d uct s or wit h dra w fr o m trial will n ot be re place d.  
7. 3   
L ost t o f oll o w -u p  
A s u bject will be c o nsi dere d l ost t o f oll o w -u p if he or s he re peat e dl y fails t o ret ur n f or sc he d ule d 
visits a n d is u na ble t o be c o ntacte d b y t he site.  
T he f oll o wi n g acti o ns m ust be ta ke n if a s u bject fails t o ret ur n t o t he site f or a re q uire d visit:  
•  T he site m ust atte m pt t o c o ntact t he s u bject a n d resc he d ule t he misse d visit as s o o n as 
p ossi ble a n d c o u nsel t he s u bject o n t he i m p orta nce of mai ntai ni n g t h e assi g ne d visit 
sc he d ule a n d ascertai n w het her or n ot t he s u bject wis hes t o a n d/ or s h o ul d c o nti n ue i n t he 
trial. 
•  Bef ore a s u bj ect is dee m e d l ost t o f oll o w -u p, t he i n vesti gat or or desi g nee m ust ma ke e ver y 
eff ort t o re gai n c o ntact wit h t he s u bject ( w here p ossi ble, at least t hree tele p h o ne calls a n d, if 
necessar y, a certifie d lett er t o t he s u bject’s last k n o w n maili n g a d dress or l ocal e q ui vale nt 
met h o ds). T hese c o nt act atte m pts s h o ul d be d oc u me nte d i n t he s u bject’s me dical re c or ds.  
•  S h o ul d t he s u bject c o nti n ue t o be u nreac ha bl e, he/s he will be c o nsi dere d t o ha ve wit h dra w n 
fr o m t he trial wit h a pri m ar y reas o n of `l ost t o f oll o w-u p’.  
8  
Tri al assess me nts a n d pr oce d ures  
T he f oll o wi n g s ecti o ns d escri be t he assess me nts a n d pr oce d ures, w hile t heir ti mi n g is s u m marise d 
i n t he fl o wc hart. 
•  I nf or me d c o ns e nt m ust be o btai ne d bef ore a n y trial relate d acti vit y, see Secti o n 1 0. 1. 3 . 
•  All scree ni n g e v al uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial s u bjects 
meet all i ncl usi o n criteria a n d n o ne of t he e x cl usi o n criteria.  
•  T he i n vesti gat or will mai ntai n a scree ni n g l o g t o rec or d det ails of all s u bjects scree ne d a n d 
t o c o nfir m eli gi bilit y or rec or d reas o n f or scree n fail ure, as a p plica ble.  
•  At scree ni n g, s u bjects will be pr o vi de d wit h a car d stati n g t hat t he y are partici pati n g i n a 
trial a n d gi vi n g c o nt act d etails of rele va nt site staff t hat ca n be c o ntact e d i n case of 
e mer ge n c y.  
•  A d here n ce t o t he trial d esi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he fl o wc hart, is 
esse ntial a n d re q uire d f or trial c o n d uct.   
•  Assess me nts s h o ul d be carrie d o ut acc or di n g t o t h e cli nic’s sta n dar d of practice u nless 
ot her wise s pecifie d i n t he c urr e nt secti o n. Eff orts s h o ul d be ma de t o li mit t he bias bet wee n 
assess me nts. T he s u g gest e d or der of t he ass ess me nts:  
o  Bl o o d sa m ples  
o  B o d y meas ure me nts (see Secti o n 8. 1. 1 ) 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 2
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 3  of 7 4  
 
o  Vital si g ns (see Secti o n 8. 2. 2 ) 
o  E C G  
•  Diaries will i ncl u de t he f oll o wi n g i n relati o n t o t he visit t he y s u p p ort:  
o  Re mi n ders:  
▪ t o atte n d visit fasti n g (see fl o wc hart i n Secti o n 1. 2 ) 
▪ t o ret ur n trial pr o d ucts at ne xt site visit 
▪ t o ret ur n diar y at n e xt site visit 
▪ t o re mi n d o nl y t o use eac h ca grili nti de cartri d ge t w o ti mes 
o  I nstr u cti o n o n h o w t o use t he diar y 
o  I nf or mati o n t o be c ollecte d:  
▪ d ose, date a n d site of i njecti o n of trial pr o d ucts  
▪ d ose, date, site a n d ti me of last 2 d oses pri or t o P K sa m ples 
▪ h y p o gl ycae mic e v e nts (acc or di n g t o A p pe n di x 6, Secti o n 1 0. 6 ) 
▪ healt h iss ues  
•  Re vie w of diaries, E C G, la b orat or y re p orts a n d e ye e x a mi nati o ns m ust be d oc u me nte d eit her 
o n t he d oc u me nts or i n t he s u bject’s me dical rec or ds. If clarifi cati o n of e ntries or 
discre pa n cies i n t he diari es is nee de d, t he s u bject m ust be q uesti o ne d, a n d a c o ncl usi o n 
ma de i n t he s u bject’s me dical rec or ds. Care m ust be ta ke n n ot t o bias t he s u bject.  
•  Res ults of pre g na nc y testi n g m ust be d oc u me nte d i n t he s u bject’s me dical rec or ds.  
•  Re peat sa m ples ma y be t a ke n f or  t ec h nical iss ues a n d u nsc he d ule d sa m ples or assess me nts 
ma y b e ta ke n f or safet y reas o ns. Please refer t o A p pe n di x 2 , S ecti o n 1 0. 2  f or f urt her details 
o n la b orat or y sa m ples.  
8. 1   
Effic ac y assess me nts   
Pla n ne d ti me p oi nts f or all efficac y assess me nts are pr o vi de d i n t he fl o w c hart  (S ecti o n 1. 2 ) a n d 
A p pe n di x 2, Ta ble  1 0 -1 . 
8. 1. 1   
B o d y me as ure me nts  
•  B o d y wei g ht  s h o ul d be meas ure d wit h o ut s h oes, o n a n e m pt y bl a d der a n d o nl y weari n g 
li g ht cl ot hi n g a n d rec or de d i n t he e C R F i n kil o gra ms [ k g] or p o u n ds [l b], wit h precisi o n of 
1/ 1 0 u nit (e. g. 7 5. 3 k g / 1 6 6. 0 l b). T he b o d y wei g ht s h o ul d be assesse d o n t he sa me 
cali brate d wei g hi n g s cale t hr o u g h o ut t he trial. T h e cali brati o n sta n dar d s h o ul d prefera bl y be 
o nce yearl y or reflect t he c o u ntr y re q uire me nts, u nless t he ma n ufact urer cert ifies t hat 
cali brati o n of t he wei g hi n g scale is vali d f or t he lifeti me of t he scale.  
•  Hei g ht  is meas ure d wit h o ut s h oes i n ce nti metres or i nc hes ( o ne deci mal). B MI will be 
calc ulate d i n t he e C R F fr o m scree ni n g dat a.  
8. 1. 2   
C o nti n u o us gl uc ose m o nit ori n g  
S u bjects wil l be e q ui p pe d wit h a C G M de vice at t he site visits ( V 1 , V 1 1, V 15 ). F or eac h of t he 
C G M assess me nt peri o ds t he se ns or m ust be w or n f or 1 0 f ull da ys a n d b e re m o ve d at t he visits or as 
cl ose t o t he visits as p ossi ble at t he site visits (V 2, V 1 2, V 1 6 ). T his nee ds t o be c o nsi dere d w he n 
pla n ni n g t he visits w here t he se ns or is t o be fitte d a n d re m o ve d.  
T he C G M s yste m use d i n t his trial will be t he De xc o m G 6 ® . 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 3
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 4  of 7 4  
 
T he C G M rea di n gs will be bli n de d t o b ot h t he s u bject a n d i n vesti gat or a n d will n ot be use d f or a n y 
d ose a dj ust me nts or h y p o gl ycae mic e pis o de re p orti n g.  
If a s u bject wit h dra ws c o nse nt d uri n g t he tri al, a site visit s h o ul d be sc he d ule d i n or der t o re m o ve 
t he C G M se ns or a n d u pl oa d t he data fr o m t he recei ver. 
C G M fitti n g a n d tr ai ni n g  
T he site staff will cl osel y s u per vise a n d assist wit h fitti n g of t he se ns or a n d tra ns mitter o n t he 
s u bject d uri n g t h e site visits. Trai ni n g i n t he C G M is t he res p o nsi bilit y of t he i n vesti gat or or site 
staff at t he rele va nt visits. T he site s h o ul d e ns ure t he s u bject is trai ne d i n c h a n gi n g t he se ns or at 
h o me i n case t he C G M s e ns or nee ds t o b e c ha n ge d after fitti n g at site i n case it falls off. All 
s u bjects will be pr o vi de d wit h a n e xtra se ns or t o bri n g h o me i n case t he y n ee d t o re -fit t he se ns or. 
F or i nf or m ati o n o n fitti n g, a n d c ha n gi n g  of t he C G M parts, please refer t o t he I n v esti gat ors C G M 
ma n ual a n d S u bject g ui d e pr o vi de d.  
C G M u pl o a d  
T he s u bject will ret ur n t h e recei ver t o site staff at visit ( V 2, V 1 2,  V 1 6) f or data u pl oa d. Dat a st ore d 
o n t he C G M recei ver m ust be u pl oa de d at t he site  b y t he site staff t o t he C G M s oft ware f oll o wi n g 
t he i nstr ucti o n pr o vi de d t o t he sites. T he u pl oa d will be d oc u me nte d b y t he s yste m directl y. 
T he serial n u m ber of t he C G M recei ver m ust be rec or de d a n d c o nfir me d i n t he e C R F at t he start of 
eac h C G M peri o d. I n cas e t he C G M recei ver is bei n g re pl ace d, t h e serial n u m ber s h o ul d be 
u p date d.  
8. 1. 3   
Cli nic al effic ac y l a b or at or y assess me nts  
All pr ot oc ol -re q uir e d la b orat or y assess me nts, as defi ne d i n A p pe n di x 2 (Secti o n 1 0. 2 ), m ust be 
c o n d ucte d i n acc or da nce wit h t he fl o wc hart a n d t he la b orat or y m a n ual.  
8. 2   
S afet y assess me nts   
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he fl o wc h art ( Secti o n 1. 2 ). 
A c o nc o mit a nt ill ness  is a n y ill ness t hat is alrea d y prese nt at t he ti me p oi nt fr o m w hic h A Es are 
c ollecte d or f o u n d as a res ult of a scree ni n g pr oce d ure or ot her trial pr oce d ures perf or me d bef ore 
e x p os ure t o trial pr o d uct s.  
Me dic al hist or y is a me dical e ve nt t hat t he s u bject e x perie nce d pri or t o t he ti me p oi nt fr o m w hic h 
A Es are c ollecte d . O nl y rele va nt a n d si g nifica nt me dical hist or y as j u d ge d b y t he i n vesti gat or 
s h o ul d be re p orte d i n t he eC R F  at t he scree ni n g visit. Fi n di n gs of s pecific me dical hist or y (dia betes 
hist or y, c o m or bi dities a n d hist or y of car di o vas c ular disease)  s h o ul d be des cri be d i n t he desi g nat e d 
f or ms. 
I n case of a n a b n or mal a n d cli nicall y si g nifica nt fi n di n g f ulfilli n g t he defi niti o n of a c o nc o mita nt 
ill ness or me dical hist or y, t he i n vesti gat or m ust rec or d t he fi n di n g o n t he Me dical Hist or y/ 
C o nc o mita nt Ill ness f or m.   
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 4
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 5  of 7 4  
 
8. 2. 1   
P h ysic al e x a mi n ati o ns  
A p h ysic al e xa mi nati o n will i ncl u de assess me nts of:  
•  Ge neral a p peara n ce  
•  Hea d, ears, e yes, n ose, m o ut h, t hr oat, nec k  
•  Res pirat or y s yst e m  
•  Car di o vasc ular s yste m  
•  A b d o me n  
•  M usc u l os keletal s yste m 
•  Ce ntral a n d peri p h eral n er v o us s yste m  
•  S ki n  
•  T h yr oi d gla n d  
•  L y m p h n o de p al pati o n  
•  Breast (fe m ales o nl y ). 
I n v esti gat ors s h o ul d pa y s pecial atte nti o n t o cli nical si g ns relate d t o pre vi o us seri o us ill nesses. 
8. 2. 2   
Vit al si g ns  
•  Bl o o d press ur e a n d p ulse  rate meas ure me nts s h o ul d be prece de d b y at least 5 mi n utes of rest 
f or t he s u bject i n a q uiet setti n g wit h o ut distracti o ns (e. g. n o use of tel e visi o n, cell p h o nes). 
•  Bl o o d press ur e a n d p ulse rate meas ure me nts will be assesse d sitti n g wit h a c o m pletel y 
a ut omate d de vice. Ma n u al tec h ni q ues m ust be use d o nl y if a n a ut o mate d de vice is n ot 
a vaila ble.  
•  Bl o o d press ur e will c o nsist of 3 s yst olic a n d diast olic bl o o d press ure meas ure me nts wit h 
i nter vals of at least 1-2 mi n utes. A n a d diti o nal f o urt h bl o o d press ure meas u re me nt m ust be 
perf or me d if t he first t w o rea di n gs o n s yst olic or diast olic bl o o d press ure differ b y 
> 1 0  m m H g. O nl y t he l ast 2 s yst olic a n d last 2 diast olic bl o o d press ure rea di n gs m ust be 
rec or de d i n t he e C R F. T h e e C R F will t he n cal c ulate t he mea n f or s yst olic a n d diast olic 
bl o o d press ure.  
•  P ulse rate will be meas ure d i n c o n necti o n t o t he bl o o d press ure meas ure m e nts. Rec or d t he 
p ulse rate f or t he last 2 bl o o d press ure meas ure m e nts i n t he e C R F. T he e C R F will calc ulate 
t he mea n p ulse rate val ues base d o n the last 2 meas ure me nts.  
8. 2. 3   
Electr oc a r di o gr a ms  
•  1 2 -lea d E C G will be o btai ne d as o utli ne d i n t he fl o wc hart usi n g a n E C G mac hi ne t hat 
a ut o maticall y calc ulat es t he heart rate a n d meas ures P R, Q R S a n d Q T -i nter vals. 
8. 2. 4   
E ye e x a mi n ati o n  
S u bjects wit h u nc o ntr olle d a n d p ot e ntiall y u nsta bl e dia betic reti n o pat h y or mac ul o pat h y are n ot 
eli gi ble as t his i n dicates reti n o pat h y t hat h as rece ntl y pr o gresse d t o a le vel t hat re q uires i nter ve nti o n 
or is a p pr oac hi n g i nter ve nti o n b ut has yet t o be br o u g ht u n der c o ntr ol.   
Res ults of a n e ye e x a mi nati o n perf or me d b y a n o p ht hal m ol o gist or a n ot her s uita bl y q ualifie d h ealt h 
care pr o vi der (e. g. o pt o m etrist) m ust be a vaila ble a n d e val uat e d b y t he i n vesti gat or bef ore 
ra n d o misati o n t o assess eli gi bilit y. T he e ye e x a mi nati o n s h o ul d be perf or me d as a f u n d us 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 5
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 6  of 7 4  
 
p h ot o gra p h y (e. g. 2 -fiel d 6 0 de gree or better, c ol o ur or re d-free) or b y slit-la m p bi o micr osc o p y 
e x a mi nati o n (e. g. usi n g a pre -c or neal or c or neal c o ntact le ns e x a mi nati o n). P har mac ol o gical p u pil -
dilati o n is a re q uire me nt u nless usi n g a di gital f u n d us p h ot o gra p h y ca mera s pecifie d f or n o n -dilate d 
e x a mi nati o n. 
If t he s u bject ha d s u c h a n e ye e x a mi nati o n perf or me d wit hi n 9 0 da ys pri or t o scree ni n g, t he 
i n vesti gat or ma y b ase his/ her e val uati o n u p o n t he res ults of t hat e xa mi nati o n. T he e x a mi nati o n m ust 
be  re peate d bef ore ra n d o misati o n if t he s u bject has e x perie nce d w ors e ni n g of vis ual f u ncti o n si nce 
t he last e x a mi nati o n. If t he a p plica ble e ye e x a mi nati o n was perf or me d bef ore t he s u bject si g ne d t he 
i nf or me d c o nse nt f or m, it m ust be d oc u me nte d t hat t he reas on f or perf or mi n g t he e x a mi nati o n was 
n ot relate d t o t his trial.  
After ra n d o misati o n a n e ye e x a mi nati o n perf or me d acc or di n g t o a b o ve m ust be perf or me d as per 
pr ot oc ol fl o wc hart  (Secti o n 1. 2 ). A n e ye e x a mi nati o n perf or me d wit hi n 2 wee ks pri or t o t he 
a p plica ble visits is acce pt a ble, pr o vi de d t hat n o cli nical s y m pt o ms s u g gesti ve of e ye dis ease h a ve 
occ urre d i n t he mea nti me i n case o f w hi c h a ne w e x a mi nati o n m ust be c o m plete d. T he i n vesti gat or 
s h o ul d i n dicate t he o utc o me of eac h e ye e x a mi nati o n i n t he e C R F.  
T he f u n d us p h ot o gra p h y or slit -la m p bi o micr osc o p y e x a mi nati o n s h o ul d be use d f or e val uati o n of 
reti n o pat h y or mac ul o p at h y. A d diti o nal e x a mi nati o ns (e. g., o ptical c o here n ce t o m o gra p h y a n d/ or 
best c orrecte d vis ual ac uit y) ca n be p erf or me d as a s u p ple me nt f or f urt her e val uati o n. H o we ver, i n 
t his trial, a d diti o nal e ye e x a mi nati o ns i ncl u di n g t he o ptical c o here nce t o m o gra p h y a n d/ or best 
c orrecte d vis ual ac uit y, ca n n ot re place t he f u n d us p h ot o gra p h y or slit -la m p bi o micr osc o p y 
e x a mi nati o n. 
Rele va nt fi n di n gs pri or t o ra n d o misati o n m ust be rec or de d as c o n c o mita nt ill ness/ me dical hist or y. 
R ele va nt fi n di n gs o cc urri n g after ra n d o misati o n s h o ul d be re p orte d as a n A E, please refer t o 
Secti o n  8. 3 . 
8. 2. 5   
Cli nic al s afet y l a b or at or y assess me nts  
All pr ot oc ol -re q uir e d la b orat or y assess me nts, as defi ne d i n A p pe n di x 2, m ust be c o n d ucte d i n 
acc or da nce wit h t he la b orat or y ma n ual a n d t he pr ot oc ol fl o wc hart.  
8. 3   
A d verse e v e nts a n d seri o us a d verse e ve nts  
T he i n vesti gat or is res p o nsi ble f or detecti n g, d oc u me nti n g, rec or di n g a n d f oll o wi n g u p o n e ve nts 
t hat meet t he definiti o n of a n A E or S A E.   
T he defi niti o n of A Es a n d S A Es ca n be f o u n d i n A p pe n di x 3, al o n g wit h a descri pti o n of A Es 
re q uiri n g a d diti o nal data c ollecti o n, please refer t o Ta ble  8 -1 . 
H y p o gl yc ae mic e pis o des  
H y p o gl ycae mic e pis o des re q uire a d diti o nal data c ollecti o n o n a h y p o gl ycae mic e pis o de f or m. As 
o p p ose d t o A Es re q uiri n g a d diti o nal dat a c ollecti o n ( Ta ble  8 -1 ), n o n-seri o us h y p o gl ycae mic 
e pis o des d o n ot re q uire a n A E f or m t o be fille d i n. If t he h y p o gl ycae mic e pis o de f ulfils t he criteria 
f or a n S A E, t he n, i n a d diti o n t o t he h y p o gl ycae mic e pis o des f or m, a n A E f or m a n d a safet y 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 6
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 7  of 7 4  
 
i nf or mati o n f or m m ust be fille d i n, please refer t o A p pe n di x 3. F or m ore i nf or mati o n o n 
h y p o gl ycae mic e pis o des, please refer t o A p pe n di x 7 . 
T a ble  8 -1   
A Es re q uiri n g a d diti o n al d at a c ollecti o n (seri o us a n d n o n -seri o us A Es)  
E ve nt t y pe   
A E re q uiri n g a d diti o n al d at a c ollecti o n  
Me dicati o n err or  
X  
Mis use a n d a b use  
X  
Ac ute gall bla d der disease  
X  
Ac ute pa ncreatitis  
X  
Dia betic reti n o pat h y 
X  
H y perse nsiti vit y reacti o n  
X  
I nj ecti o n site reacti o n 
X  
I nf or mati o n o n mis use a n d a b use A Es are ca pt ure d o n t he me dicati o n err or f or m.  
A detaile d descri pti o n of t he e ve nts me nti o ne d i n t he a b o ve ta bl e ca n b e f o u n d i n A p pe n di x 3.  
8. 3. 1   
Ti me peri o d  a n d fre q ue nc y f or c ollecti n g A E a n d S A E i nf or m ati o n  
All A Es a n d S A Es m ust be c ollecte d fr o m t he scree ni n g visit a n d u ntil t he ‘e n d of trial ’ visit at t he 
ti me p oi nts s pecifie d i n t he fl o wc hart.  
Me dical occ urre n ces t hat ta ke place or ha v e o nset pri or t o t he ti me p oi nt fr o m w hic h A Es are 
c ollecte d will be rec or de d as c o nc o mita nt ill ness/ me dical hist or y. A E a n d S A E re p orti n g ti meli nes 
ca n be f o u n d i n A p pe n di x 3. All S A Es m ust be rec or de d a n d re p orte d t o N o v o N or dis k or desi g nee 
wit hi n 2 4 h o urs, a n d t he i n ves ti gat or m ust s u b mit a n y u p d ate d S A E data t o N o v o N or dis k or 
desi g nee wit hi n 2 4 h o urs of it bei n g a v aila ble.  
I n v esti gat ors are n ot o bli gat e d t o acti vel y see k f or A E or S A E i n f or mer trial s u bjects. H o we v er, if 
t he i n vesti gat or l ear ns of a n y S A E, i n cl u di n g a d eat h, at a n y ti me after a s u bject has bee n 
disc o nti n ue d fr o m/c o m plete d t he trial, a n d t he i n v esti gat or c o nsi ders t he e v e nt t o be 
p ossi bl y/ pr o ba bl y rel ate d t o t he trial pr o d uct s or relate d t o trial partici pati o n, t he i n vesti gat or m ust 
pr o m ptl y n otif y N o v o  N or dis k.  
8. 3. 2   
Met h o d of detecti n g A Es a n d S A Es  
T he met h o d of rec or di n g, e val uati n g, a n d ass essi n g ca usalit y of A E a n d S A E a n d t he pr oce d ures f or 
c o m pleti n g a n d tr a ns mitti n g S A E re p orts are pr o vi de d i n A p pe n di x 3 ( Secti o n 1 0. 3 ). 
Care s h o ul d be ta ke n n ot t o i ntr o d uce bias w he n d etecti n g A Es a n d/ or S A Es. O pe n -e n d e d a n d n o n -
lea di n g v er bal q u esti o ni n g of t he s u bj ect is t he preferre d met h o d t o i n q uire a b o ut e ve nts. 
8. 3. 3   
F oll o w -u p of A Es a n d S A Es  
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y f oll o w eac h s u bject at 
s u bse q ue nt visits/c o ntacts. All S A Es, s h o ul d be f oll o we d u ntil fi nal o utc o me of t he e v e nt or t he 
s u bject is l ost t o f oll o w-u p as descri be d i n Secti o n 7. 3 . F urt her i nf or mati o n o n f oll o w-u p a n d fi nal 
o utc o me of e ve nts is gi ve n i n A p pe n di x 3.   
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 7
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 8  of 7 4  
 
8. 3. 4   
Re g ul at or y re p orti n g re q uire me nts f or S A Es  
Pr o m pt n otificati o n b y t he i n vesti gat or t o N o v o N or dis k or desi g n ee of a S A E is esse ntial s o t hat 
le gal o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of s u bjects a n d t he safet y of a trial 
pr o d uct u n der cli nical i n vesti gati o n are met.   
N o v o N or dis k has a le gal res p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b o ut t he safet y of a trial pr o d uct u n der cli nical i n vesti gati o n. N o v o N or dis k 
will c o m pl y wit h c o u ntr y -s pecific re g ulat or y re q uire me nts relati n g t o safet y re p orti n g t o t he 
re g ulat or y a ut h orit y, I R B/I E C, a n d i n vesti gat ors. T his als o i ncl u des s us pecte d u ne x pecte d seri o us 
a d verse reacti o ns ( S U S A Rs).  
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a S A E or ot her s pecific safet y 
i nf or mati o n (e. g. s u m mar y or listi n g of S A Es) fr o m N o v o N or dis k will re vie w a n d t he n file it al o n g 
wit h t he i n vesti gat or’s br oc h ure a n d will n otif y t h e I R B/I E C, if a p pr o priate acc or di n g t o l ocal 
re q uire me nts. 
8. 3. 5   
Pre g n a nc y  
Details of pre g n a ncies i n fe male s u b jects will be c ollecte d after scree ni n g visit a n d u ntil  ‘e n d of 
trial’ visit ( V 1 7). If a fe m ale s u bject bec o mes pre g na nt, t he i n vesti gat or s h o ul d i nf or m N o v o 
N or dis k wit hi n 1 4 cale n dar da ys of lear ni n g of t he pre g na nc y a n d s h o ul d f oll o w t he pr oce d ures 
o utl i ne d i n A p pe n di x 4 ( Secti o n 1 0. 4 ). 
8. 3. 6   
C ar di o v asc ul ar a n d de at h e ve nts  
Car di o vasc ular a n d deat h e ve nts will be ha n dle d a n d re p orte d acc or di n g t o Secti o n 8. 3 . 
8. 3. 7   
H y perse nsiti vit y  
I n t he e ve nt of a s yste mic h y p erse nsiti vit y reacti o n t o trial pr o d ucts, t he s u bject s h o ul d be calle d i n 
as s o o n as p ossi ble t o ha ve a d diti o nal bl o o d sa m ples ta ke n i n or der t o a nal ys e t he f oll o wi n g 
para meters:  
•  tr y ptas e  
•  t otal i m m u n o gl o b uli n E (I g E) a nti b o dies 
•  a nti-ca grili nti de I g E a nti b o dies   
•  a nti-se ma gl uti de I g E a nti b o dies  
T he bl o o d sa m pli n g s h o ul d be re peate d 2 -4 wee ks f oll o wi n g o nset of t he s yste mic h y perse nsiti vit y 
reacti o n. If p ossi ble, t he a b o ve-me nti o ne d a nal yses s h o ul d als o be perf or me d o n t he P K sa m ple 
fr o m visit 4 ( wee k 4). 
F or details r elate d t o bl o o d sa m pli n g, plas ma pre parati o n a n d st ora ge, please refer t o t he l a b orat or y 
ma n ual.  
F or rete nti o n of resi d ual h y perse nsiti vit y sa m ples, please refer t o A p pe n di x 6, S ecti o n 1 0. 6 .  
8. 3. 8   
Tec h nic al c o m pl ai nts  
Tec h nical c o m plai nts will be c ollecte d f or all pr o d ucts liste d o n t he tec h nical c o m plai nt f or m.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 8
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 9  of 7 4  
 
I nstr u cti o ns f or re p orti n g tec h nical c o m plai nts ca n be f o u n d i n A p pe n di x 5, S ecti o n 1 0. 5 . 
I n or der f or N o v o N or dis k t o perf or m a c o m plete i n vesti gatio n of re p orte d S A Es, N o v o N or dis k 
mi g ht as k t he i n vesti gat or t o c o m plete a tec h nical c o m plai nt f or m.   
8. 4   
Tre at me nt of o ver d ose  
O ver d oses of u p t o 6. 0 m g has b ee n o bser ve d wit h ca grili nti de treat me nt i n t he p hase 2 cli nical trial 
( N N 9 8 3 8-4 4 3 3). T h e o ver d oses w ere relate d t o n o n -seri o us A Es, m ost c o m m o nl y GI A Es a n d 
dizzi ness.  
Se ma gl uti de o ver d oses of u p t o 4. 0 m g i n a si n gle d ose, a n d u p t o 4. 0 m g i n a wee k ( b y m ulti ple 
a d mi nistrati o ns) ha ve bee n re p ort e d i n cli nical trials ( S T E P -pr o gra m me). T he m ost c o m m o nl y 
re p orte d A E was na us ea. All s u bjects rec o vere d wit h o ut c o m plicati o ns. 
T here is n o s pecific a nti d ote f or o ver d ose wit h eit her se ma gl uti de or ca grili nti de. I n t he e ve nt of a n 
o ver d ose, a p pr o priate s u p p orti ve treat me nt s h o ul d be i nitiate d acc or di n g t o s u bject ’s cli nical si g ns 
a n d s y m pt o ms.  
Acci de ntal o v er d ose m ust be re p orte d as a me dicati o n err or. I nte nti o nal o v er d ose m ust be re p orte d 
as mis use a n d a b use, please refer t o Secti o n 8. 3  a n d A p pe n di x 3 f or f urt her details.  
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or s h o ul d cl osel y m o nit or t he s u bject f or o ver d ose-relate d 
A E/ S A E  a n d la b orat or y a b n or malities, c o nsi deri n g t he l o n g half -life of ca grili nti de a n d 
se ma gl uti de.  
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y t h e i n vesti gat or base d o n 
t he cli nical e val uati o n of t he s u bject. 
F or m ore i nf or mati o n o n  o ver d ose, als o c o ns ult t he c urre nt versi o n of t he  ca grili nti de a n d 
se ma gl uti de i n vesti gat or’s br oc h ure. 
8. 5   
P h ar m a c o ki netics  
Plas ma sa m ples t o be a nal yse d f or plas ma c o n ce ntrati o n of se ma gl uti de a n d ca grili nti de will be 
c ollecte d at ti me p oi nts as s pecifie d i n t he fl o w c hart (see Secti o n 1. 2  a n d 1 0. 2 ). Bl o o d sa m ples f or 
meas ure me nt of ca grili nti de a n d se ma gl uti de c o n ce ntrati o n m ust be dra w n bef ore d osi n g of trial 
pr o d uct ( C tr o u g h meas ure me nt).   
Se parate plas m a sa m ples will be c ollecte d f or  ca grili nti de a n d se ma gl uti de. Sa m pli n g a n d ha n dli n g 
will be perf or me d as detaile d i n t he la b orat or y ma n ual.  
Se ma gl uti de a n d ca grili nti de will be assa ye d i n pl as ma b y vali date d ass a ys. Details of t he 
bi oa nal ysis will be o utli ne d i n a bi oa nal ytical st u d y p la n. 
F or rete nti o n of resi d ual ca grili nti de P K sa m ples, please refer t o A p pe n di x 6, S ecti o n 1 0. 6 . 
8. 6   
P h ar m a c o d y n a mi cs  
N ot a p plica ble f or t his trial.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
3 9
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 0  of 7 4  
 
8. 7   
Ge neti cs  
N ot a p plica ble f or t his trial.  
8. 8   
Bi o m ar kers  
C ollecti o n of sa m ples f or bi o mar ker researc h is part of t his trial t o s u p p ort t he effi cac y o bj ecti ves. 
T he f oll o wi n g s a m ples m ust be c ollecte d a n d pr ocesse d i n acc or da n ce wit h t he la b orat or y ma n ual 
a n d A p p e n di x 2, S ecti o n 1 0. 2  : 
Bi o mar kers li n ke d t o car di o vasc ular ris k a n d i nfl a m mati o n:  
•  Hi g h se nsiti ve C -reacti ve pr otei n ( hs C R P) 
Bi o mar kers li n ke d t o a p p etite re g ulati o n:  
•  Le pti n  
•  S ol u ble le pti n rece pt or  
8. 9   
I m m u n o ge nicit y assess me nts 
N ot a p plica ble f or t his trial.  
8. 1 0   
He alt h ec o n o mics   
N ot a p plica ble f or t his trial.  
9  
St atistic al c o nsi der ati o ns   
9. 1   
St atistic al h y p ot heses  
N o c o nfir mat or y statistical h y p ot hesis testi n g  will be d o ne i n t his trial. Treat me nt differe n ces will 
be re p ort e d wit h 2 -si de d 9 5 % c o nfi de n ce i nter vals. 
9. 2   
S a m ple size deter mi n ati o n   
As t he prese nt st u d y is e x pl orat or y t he sa m ple size calc ul ati o n is n ot base d o n c o nfir mat or y testi n g 
b ut ai ms at q ua ntif yi n g t he ma g nit u de of e x pecte d variati o n i n t he treat me nt differe n ce f or t he 
pri mar y e n d p oi nt s u p p orti n g t he pri mar y o bjecti ve. F or t he pri mar y esti ma n d a sta n dar d de viati o n 
of 0. 9 ( S T E P 2) or 1 is ass u me d f or H b A 1c c ha n ge fr o m baseli ne t o wee k 3 2. Wit h 3 0 r a n d o mise d 
s u bjects per treat me nt ar m a p pr o xi matel y 8 0 % pr o ba bilit y is ac hie ve d f or o btai ni n g a 9 5 % 
c o nfi de nce i nter val of t h e treat me nt differe n ce wit h half -wi dt h 0. 5 a n d 0. 5 6 % -p oi nts, res pecti vel y. 
T he ac hie va ble half -wi dt h ( wit h r o u g hl y 8 0 % pr o ba bilit y)  vers us sa m ple size is s h o w n i n   
Fi g ure  9 -1  f or differe nt c h oices of sa m ple size. Base d o n t his, a sa m ple size of 3 0 ra n d o mise d 
s u bjects per treat me nt ar m, i.e. a t otal of 9 0 ra n d o mise d s u bjects, is c o nsi dere d s ufficie nt.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 0
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 1  of 7 4  
 
Fi g ure  9 -1 . H alf-wi dt h of 9 5 % CI f or tre at me nt differe nce o n H b A 1c c h a n ge o bt ai ne d wit h 
8 0 % p o wer vers us s a m ple size b y st a n d ar d de vi ati o n (st d).  
 
9. 3   
P o p ul ati o ns f or a n al yses   
T he f oll o wi n g p o p ul ati o n s are defi ne d : 
P o p ul ati o n  
Descri pti o n  
F ull a nal ysis set ( F A S)   
All s u bj ects ra n d o mise d.  
Safet y a nal ysis set ( S A S)   
All s u bj ects ra n d o ml y assi g ne d t o trial treat me nt a n d w h o ta ke at least 1 d ose of trial 
pr o d uct.  
T he s u bjects or o bser vati o ns t o be e x cl u de d fr o m t he a nal ysis sets a n d t he reas o ns f or t heir  
e x cl usi o n m ust be d oc u me nte d bef ore u n bli n di n g a n d will be descri be d i n t he C T R. Efficac y 
e n d p oi nts will be a nal ys e d usi n g t he F A S a n d safet y e n d p oi nts will be a nal ys e d usi n g t he S A S. F or 
b ot h t he pri mar y esti ma n d a n d t he a d diti o nal esti ma n d, s u bjects c o ntri b ute t o t he a nal ysis acc or di n g 
t o t he ra n d o mise d treat m e nt. 
T hree o bser vati o n peri o ds are defi ne d f or eac h s u bject:  
•  T he i n -trial peri o d is defi ne d as t he ti me i nter val fr o m date of ra n d o misati o n t o date of last 
c o ntact wit h trial site.  
•  T he o n -treat me nt peri o d is a s u bset of t he ‘i n-trial’ o bser vati o n peri o d a n d re pres e nts t he 
ti me peri o d w here s u bjects are c o nsi dere d e x p ose d t o trial pr o d uct. T he o bser vati o n peri o d 
starts at t he date of first d ose of trial pr o d uct a n d e n ds at t he first date of a n y of t he 
f oll o wi n g: 
o  T he date of l ast d ose of trial pr o d uct + 3 5 da ys f or A Es a n d h y p o gl ycae mic e pis o des/ 
+ 1 4 da ys f or ot h er e n d p oi nts  
o  T he e n d -d ate f or t h e ‘i n -trial’ o bser vati o n peri o d 
T he o n -treat me nt peri o d will be use d for re p orti n g A Es  a n d h y p o gl ycae mic e pis o des . 
T he o n -treat me nt wit h o ut resc ue m e dicati o n peri o d is a s u bset of t he ‘ o n-treat me nt’ o bser vati o n 
peri o d a n d re pres e nts t he ti me peri o d w here s u bjects are c o nsi dere d e x p ose d t o trial pr o d uct b ut  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 1
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 2  of 7 4  
 
ha ve n ot i nitiate d  a n y res c ue me dicati o ns. T he o bser vati o n peri o d starts at t he date of first d ose  of 
trial pr o d uct a n d e n ds at t he first date of a n y of t he f oll o wi n g: 
•  I nitiati o n of resc ue m e dicati o n 
•  T he last date of t he o n -tr eat me nt peri o d 
T he i n -trial a n d o n-tr eat me nt peri o ds defi ne t he patie nt years of o bs er vati o n ( P Y O) a n d patie nt 
years of e x p os ure ( P Y E), res pecti vel y, as t he t otal ti me d urati o n i n t he peri o ds.  
Data p oi nts c ollecte d o utsi de a n o bser vati o n peri o d will n ot be i ncl u de d i n t he a nal ysis. Bas eli ne 
data will al wa ys be i ncl u de d i n a n o bser vati o n peri o d.  
F or t he pri mar y esti ma n d, t he o n -treat me nt wit h o ut resc ue me di cati o n peri o d will be use d f or 
re p orti n g of efficac y e n d p oi nts. F or t he a d diti o nal esti ma n d, data fr o m t he i n-trial o bser vati o n 
peri o d is use d.  
9. 4   
St atist ic al a n al yses 
T he statistical a nal ysis pla n ( S A P) will be fi nalise d pri or t o t he first a d mi nistrati ve D B L a n d it will 
i ncl u de a m ore tec h nical a n d detaile d des cri pti o n of t he statistical a nal yses descri be d i n t his secti o n. 
T his secti o n is a s u m mar y of t he pl a n ne d statistical a nal ys es of t he m ost i m p orta nt e n d p oi nts 
i ncl u di n g pri mar y e n d p oi nt. 
9. 4. 1   
Ge ner al c o nsi der ati o ns  
H a n dli n g of missi n g b aseli ne d at a  
T he latest a vaila ble m eas ure me nt at or pri or t o ra n d o misati o n is use d as t he baseli ne meas ure me nt.  
If n o meas ure me nts ha ve bee n o btai ne d at or pri or t o ra n d o misati o n, t he mea n val ue at 
ra n d o misati o n acr oss all s u bjects is use d as t he baseli ne val ue. 
9. 4. 2   
Pri m ar y e n d p oi nt  
A n al ysis a d dressi n g t he pri m ar y esti m a n d  
H b A 1c ( %-p oi nt) c ha n ge fr o m baseli ne will be a n al yse d  usi n g a mi x e d m o del f or re p eate d 
meas ure me nts ( M M R M). Wee k 3 2 assess me nts f or retrie v e d dr o p -o uts are n ot use d i n t his a nal ysis. 
T he M M R M will use assess me nts o nl y fr o m s u bjects w h o are t a ki n g t h e ra n d o mise d treat me nt u ntil 
e n d of treat me nt or u ntil first  disc o nti n uati o n of ra n d o mise d treat me nt defi n e d as 2 c o nsec uti ve 
misse d d oses. T he deri ve d date of t he sec o n d c o ns ec uti ve misse d d ose will be use d as t he lat est date 
f or usi n g assess me nts i n t his M M R M. F or s u bjects w h o i nitiate resc ue m e dicati o n bef ore 
c om pleti o n or first disc o nti n uati o n of ra n d o mise d treat me nt, t he date of starti n g resc ue me di cati o n 
will be use d as latest date f or usi n g assess me nts i n t his M M R M. T he M M R M will be fitte d usi n g 
H b A 1c c ha n ge wit h treat me nt a n d stratificati o n fact or as fact ors  a n d b aseli ne H b A 1c as c o variat e –  
all neste d wit hi n visit. A n u nstr uct ure d c o v aria n ce matri x f or meas ure me nts wit hi n t he sa me s u bject 
will be e m pl o ye d. If t his m o del is n ot feasi ble, t he m o del will be si m plifie d b y first e xcl u di n g t h e 
stratificati o n fact or fr o m t he m o del a n d, if necessar y, usi n g a c o m p o u n d s y m metr y c o v aria n ce 
matri x.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 2
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 3  of 7 4  
 
T he prese nt A N C O V A -M M R M m o del will be use d t o deri ve esti mates of treat me nt differe nces 
wit h 9 5 % c o nfi de nce i nter vals f or ca grili nti de 2. 4 m g/se ma gl uti de 2. 4 m g vers us se ma gl uti de 
2. 4  m g ( pri mar y o bjecti v e) a n d vers us ca grili nti de 2. 4 m g (sec o n dar y o bjecti ve) t o get h er wit h p -
val ues f or t he 2 -si de d tests of n o treat me nt differe nces. 
A n al yses a d dressi n g t he a d diti o n al esti m a n d  
T he a nal ysis m o del f or c ha n ge i n H b A 1c ( %-p oi nt) is a n A N C O V A wit h ra n d o mise d treat me nt a n d 
stratificati o n fact or as fact ors a n d baseli ne H b A 1c as a c o variate. T he a d diti o nal esti ma n d will be 
base d o n t he F A S usi n g all a vaila ble wee k 3 2 meas ure me nts fr o m t he i n -tri al o bser vati o n peri o d. 
Missi n g wee k 3 2 d ata  will be i m p ute d fr o m retrie ve d s u bjects off treat me nt b y m ulti ple i m p utati o n 
( R D MI) usi n g a n A N C O V A m o del wit h t he sa me fact ors a n d c o variate as f or t he a n al ysis m o del. If 
necessar y f or feasi bilit y, t his m o del will be si m plifie d b y e x cl u di n g t he stratific ati o n fact or.  
T he prese nt A N C O V A -R D MI m o d el will be use d t o deri ve esti mates of treat me nt differe nces wit h 
9 5 % c o nfi de n ce i nter vals f or ca grili nti de 2. 4 m g/s e ma gl uti de 2. 4 m g v ers us se ma gl uti de 2. 4 m g 
( pri mar y o bjecti ve) a n d v ers us ca grili nti de 2. 4 m g (sec o n dar y o bjecti ve) t o get her wit h p -val u es f or 
t he 2-si de d tests of n o treat me nt differe nces. 
9. 4. 3   
Sec o n d ar y e n d p oi nt(s)  
9. 4. 3. 1   
C o nfir m at or y s ec o n d ar y e n d p oi nt(s)  
N ot a p plica ble f or t his trial.  
9. 4. 3. 2   
S u p p orti ve sec o n d ar y e n d p oi nts  
C G M e n d p oi nts 'ti me i n tar get r a n ge' a n d 'ti me a b o ve tar get ra n ge' will be calc ulate d as 1 0 0 ti mes 
t he n u m ber of rec or de d meas ure me nts i n t he gi ve n gl ycae mic ra n ge, di vi d e d b y t h e t otal n u m ber of 
rec or de d meas ure me nts.  
A nal ysis of ot h er sec o n d ar y e n d p oi nts are descri be d i n t he S A P.  
9. 4. 4   
E x pl or at or y e n d p oi nts 
A nal ys es of e x pl orat or y e n d p oi nts are des cri be d i n t he S A P.  
9. 4. 5   
Ot her s afet y a n al yses  
All safet y a nal yses will be ma de o n t he safet y a n al ysis set. T he sta n dar d safet y assess me nts ( A Es, 
safet y la b orat or y para met ers, vital si g ns, et c.) will be re p orte d descri pti vel y , i ncl u di n g a n y n ota bl e 
c ha n ges of cli nical i nterest i n la b orat or y p ara meters.  
9. 4. 6   
Ot her a n al yses   
F or ot her a nal yses, pleas e refer t o t he S A P.   
9. 4. 6. 1   
P h ar m a c o ki netic m o delli n g  
Data fr o m t he tri al ma y b e use d f or e x pl orat or y p h ar mac o ki netic a nal ysis as  nee de d.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 3
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 4  of 7 4  
 
9. 5   
I nteri m a n al yses 
I n or der t o pre p o ne a p hase 3 st o p/ g o decisi o n a n d i nitiate p ote ntial p hase 3 pla n ni n g, i nteri m 
a nal ys es are pla n ne d at w ee k 2 0 f or t h e f oll o wi n g e n d p oi nts:  
•  C ha n ge fr o m bas eli ne t o wee k 2 0 i n H b A1c  
•  C ha n ge fr o m bas eli ne t o wee k 2 0 i n F P G 
•  C G M e n d p oi nts: Mea n gl uc ose c ha n ge fr o m baseli ne t o wee k 2 0, Ti me i n t ar get ra n ge at 
wee k 2 0 a n d ti me a b o ve tar get ra n ge at w ee k 2 0.  
•  C ha n ge fr o m bas eli ne t o wee k 2 0 i n b o d y wei g ht  
A n ot her i nteri m ma y be c o n d ucte d after last s u bject's last treat me n t i n case t he i nteri m at wee k 2 0 
was i nc o ncl usi ve.  
A mi ni m u m n u m ber of N o v o N or dis k pers o n nel will be u n bli n de d t o perf or m t he i nteri m 
e val uati o ns. After u n bli n di n g, t hese p e o ple ca n n ot be i n v ol ve d i n dail y trial acti vities  u ntil D B L . N o 
c ha n ge i n trial de si g n ca n occ ur a n d t h e trial will n ot be st o p pe d f or eit her p ositi ve efficac y or 
f utilit y at t he i nteri m e val uati o ns. It is n ot c o nsi dere d a pr ot oc ol de vi ati o n if a n i nteri m a nal ysis is 
n ot perf or me d. F urt her i nf or mati o n o n t he i nteri m e val uati o ns will be s pecifie d i n a n i nteri m c harter 
bef ore u n bli n di n g.  
9. 6   
D at a m o nit ori n g c o m mittee  
N ot a p plica ble f or t his trial.  
9. 7   
Re p orti n g of t he m ai n p art of t he tri al  
A D B L is pla n n e d s h ortl y after last s u bject last visit . T he trial will be re p orte d after t his D B L.  
 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 4
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 5  of 7 4  
 
1 0  S u p p orti n g d oc u me nt ati o n a n d o p er ati o n al c o nsi der ati o ns  
1 0. 1   
A p pe n di x 1: Re g ul at or y, et hic al, a n d tri al o versi g ht c o nsi der ati o ns  
1 0. 1. 1   
Re g ul at or y a n d et hic al c o nsi der ati o ns  
•  T his trial will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g:  
•  C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he Declarati o n 
of Helsi n ki 2 8 a n d a p plica ble I C H G o o d Cli nical Practice ( G C P) G ui deli ne 2 9 
•  A p plica ble la ws a n d re g ulati o ns  
•  T he pr ot oc ol, i nf or me d c o n se nt f or m, i n vesti gat or’s br oc h ure (as a p plica bl e) a n d ot her 
rele va nt d oc u m e nts (e. g. a d vertise me nts) m ust be s u b mitte d t o a n I R B/I E C a n d re vie we d 
a n d a p pr o ve d b y t he I R B/I E C bef ore t he trial is i nitiate d.  
•  Re g ulat or y a ut h orities will recei ve t he cli nical t rial a p plicati o n, pr ot oc ol a m e n d me nts, 
re p orts o n S A Es, a n d t he C T R acc or di n g t o nati o n al re q uire m e nts. 
•  A n y a me n d me nts t o t he pr ot oc ol will re q uire I R B/I E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma d e t o t he trial desi g n, e x ce pt f or c ha n ges necess ar y t o eli mi nate a n i m me diate 
safet y hazar d t o trial s u bj ects. 
•  Bef ore a site is all o w e d t o start scree ni n g s u bjects, writte n n otificati o n fr o m N o v o N or dis k 
m ust be recei v e d.  
•  T he i n vesti gat or will be res p o nsi ble f or:  
o  pr o vi di n g writte n s u m maries of t he stat us of t h e tri al a n n uall y or m ore fre q u e ntl y i n 
acc or da nce wit h t he re q uire me nts, p olicies, a n d pr oce d ures esta blis he d b y t he 
I R B/I E C a n d/ or re g ulat or y a ut h orities 
o  n otif yi n g t he I R B/I E C of S A Es or ot her si g nifi ca nt safet y fi n di n gs as re q uire d b y 
I R B/I E C pr oce d ures 
o  pr o vi di n g o versi g ht of t h e c o n d uct of t he trial at t he site a n d a d here n ce t o 
re q uire me nts of I C H g ui deli nes, t he I R B/I E C, a n d all ot her a p plica ble l o cal 
re g ulati o ns 
o  e ns uri n g s u b missi o n of t he C T R s y n o psis t o t he I R B/I E C  
o  re p orti n g a n y p ote ntial seri o us breac h es t o t he s p o ns or i m me diatel y after disc o ver y  
1 0. 1. 2   
Fi n a nci al discl os ure  
I n v esti gat ors a n d s u b-i n v esti gat ors will pr o vi de N o v o N or dis k wit h s uffici e nt, acc urate fi na ncial 
i nf or mati o n as re q u este d t o all o w N o v o N or dis k t o s u b mit c o m plete a n d acc urate fi na ncial 
certificati o n or discl os ure state me nts t o t he a p pr o priate re g ul at or y a ut h orities. I n v esti gat ors are 
res p o nsi ble f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t h e c o urse of t he trial a n d o ne 
year after c o m pleti o n of t he trial.  
Verificati o n u n der d iscl os ures per C o de of Fe deral Re g ulati o ns ( C F R) of Fi na ncial C o nflict of 
I nterest. 
1 0. 1. 3   
I nf or me d c o nse nt pr ocess 
•  T he i n vesti gat or or his/ her re prese nt ati ve will e x plai n t he nat ure of t he trial t o t he s u bject 
a n d a ns wer all q uesti o ns re gar di n g t he tri al.   
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 5
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 6  of 7 4  
 
•  T he i n vesti gat or m ust e ns ure t he s u bject a m ple ti me t o c o me t o a decisi o n w het her or n ot t o 
partici pate i n t he trial.   
•  S u bjects m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y.  
•  S u bjects m ust be i nf or me d a b o ut t heir pri vac y ri g hts.  
•  S u bjects will be re q uire d t o si g n a n d date a state m e nt of i nf or me d c o ns e nt t hat meets t he 
re q uire me nts of l o cal re g ulati o ns, I C H g ui deli nes 2 9, Declarati o n of Helsi n ki2 8 a n d t he 
I R B/I E C or site. 
•  T he me dical r ec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o ns e nt was o btai ne d 
bef ore a n y trial r el ate d acti vit y a n d t he date w he n t he writte n c o nse nt w as o btai ne d. T he 
a ut h orise d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n a n d date t he i nf or me d 
c o nse nt f or m bef ore a n y trial relate d acti vit y.  
•  T he res p o nsi bilit y of see ki n g i nf or me d c o nse nt m ust re mai n wit h t he i n vesti gat or, b ut t he 
i n vesti gat or ma y d ele gat e t he tas k t o a me dicall y q ualifie d pers o n, i n acc or da nce wit h l ocal 
re q uire me nts. 
•  S u bjects m ust be re -c o ns e nte d t o t he m ost c urre nt versi o n of t he i nf or me d c o nse nt f or m s 
d uri n g t heir p artici pat i o n i n t he trial. 
•  A c o p y of t he i nf or me d c o nse nt f or ms m ust be pr o vi de d t o t he s u bject.  
1 0. 1. 4   
I nf or m ati o n t o s u bjects d uri n g tri al 
T he site will be offere d a c o m m u nicati o n pac ka ge f or t he s u bject d uri n g t h e c o n d uct of t he trial. 
T he pac k a ge c o nt e nt is iss ue d b y  N o v o N or dis k. T he c o m m u nicati o n pac k a ge will c o ntai n writte n 
i nf or mati o n i nte n de d f or distri b uti o n t o t he s u bjects. T he writte n i nf or mati o n will be tra nslate d a n d 
a dj uste d t o l ocal re q uir e me nts a n d distri b ute d t o t he s u bject at t he discreti o n of t he i n ves ti gat or. T he 
s u bject ma y recei ve a “ welc o me t o t he trial letter” a n d a “t ha n k y o u f or y o ur partici pati o n letter” 
after c o m pleti o n of t he trial. F urt her, t he s u bject ma y recei ve ot her writte n i nf or mati o n d uri n g t he 
trial.  
All writte n i nf or mati o n t o s u bject s m ust be se nt t o I R B/I E C f or a p pr o val/fa v o ura ble o pi ni o n a n d t o 
re g ulat or y a ut h orities f or a p pr o val or n otificati o n acc or di n g t o l ocal re g ulati o ns. 
1 0. 1. 5   
 D at a pr otecti o n  
•  S u bjects will be assi g ne d a 6 -di git u ni q ue i de ntifier, a s u bject n u m ber. A n y s u bject rec or ds 
or datasets t hat are tra nsferre d t o N o v o N or dis k will c o ntai n t he i de ntifier o nl y. N o direct 
i de ntifiers fr o m t he s u bject are tra nsferre d t o N o v o N or dis k. 
•  T he s u bject a n d a n y bi ol o gical material o btai ne d fr o m t he s u bject will be i de ntifie d b y 
s u bject n um ber, visit n u m ber a n d trial I D. A p pr o priate meas ures s uc h as e ncr y pti o n or 
lea vi n g o ut certai n i de ntifiers will be e nf orce d t o pr otect t he i de ntit y of s u bjects as re q uire d 
b y l ocal, re gi o nal a n d n ati o nal re q uire me nts.   
•  T he s u bject m ust be i nf or me d a b o ut h is/ her pri vac y ri g hts, i ncl u di n g t hat his/ her pers o nal 
trial relate d dat a will be use d b y N o v o N or dis k i n acc or da nce wit h l ocal data pr otecti o n la w. 
T he discl os ure of t he d at a m ust als o be e x plai ne d t o t he s u bject.   
•  T he s u bject m ust be i nf or me d t hat his/ her me dical rec or ds ma y b e e x a mi ne d b y a u dit ors or 
ot her a ut h orise d pers o n nel a p p oi nte d b y N o v o N or dis k, b y a p pr o priate I R B/I E C me m bers, 
a n d b y i ns p ect ors fr o m re g ulat or y a ut h orities.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 6
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 7  of 7 4  
 
1 0. 1. 6   
C o m mittees st r uct ure  
1 0. 1. 6. 1   
N o v o N or dis k s afet y c o m mittee  
N o v o N or dis k will  perf or m o n g oi n g safet y s ur veilla nce. If ne w safet y si g nals are i de ntifie d, t hese 
will be e val uate d b y a n i nter nal safet y c o m mittee.  T he  safet y c o m mittee ma y rec o m me n d 
u n bli n di n g of a n y dat a f or f urt her a nal ysis, a n d i n t his case a n i nter nal trial i n de pe n d e nt a d h oc 
gr o u p will be esta blis he d i n or der t o mai ntai n t he bli n di n g of t he trial pers o n nel.  
1 0. 1. 6. 2   
Tri al s afet y gr o u p  
N ot a p plica ble f or t his trial.  
1 0. 1. 6. 3   
D at a m o nit ori n g c o m mittee  
N ot a p plica ble f or t his trial . 
1 0. 1. 6. 4   
E ve nt a dj u dic ati o n c o m mittee  
N ot a p plica ble f or t his t rial. 
1 0. 1. 7   
Disse mi n ati o n of cli nic al tri al d at a  
I nf or mati o n of t he trial will be discl ose d at cli nicaltrials. g o v a n d n o v o n or dis k-trials.c o m. It will als o 
be discl ose d acc or di n g t o ot her a p plica ble re q uire me nts, s uc h as t h ose of t he I nter n ati o nal 
C o m mittee of Me dical J o ur nal E dit ors (I C MJ E) 3 0, t he F o o d a n d Dr u g A d mi nistrati o n A me n d me nt 
Act ( F D A A A) 3 1, E ur o pea n C o m missi o n Re q uire me nts3 2 -3 4 a n d ot her rele va nt rec o m me n d ati o ns or 
re g ulati o ns. If a s u bject r e q uest t o be i ncl u de d i n t he trial via t he N o v o N ordis k e -mail c o ntact at 
t hese we b sites, N o v o N or dis k ma y discl ose t h e i n vesti gat or’s c o ntact details t o t he s u bject. As a 
res ult of i ncreasi n g re q uire me nts f or tr a ns pare nc y, s o me c o u ntries re q uire p u blic discl os ure of 
i n vesti gat or n a mes a n d t heir affiliatio ns.  
T he pri mar y c o m pleti o n date ( P C D) is t he last ass ess me nt of t he pri mar y e n d p oi nt a n d is f or t his 
trial last s u bject first treat me nt ( L S F T) + 3 2 wee ks c orres p o n di n g t o ‘e n d of treat me nt visit ( visit 
1 6). If t he last s u bject is wit h dra w n earl y, t he P C D is c o nsi dere d t he date w he n t he last s u bject 
w o ul d ha ve c o m plete d visit 1 6. T he P C D deter mi nes t he dea dli ne f or res ults discl os ure at 
cli nicaltrials. g o v acc or di n g t o F D A A A.  
1 0. 1. 8   
D at a q u alit y ass ur a nce  
1 0. 1. 8. 1   
C ase re p ort f or ms  
•  N o v o N or dis k or desi g nee is res p o nsi ble f o r t he d ata ma na ge me nt of t his trial i ncl u di n g 
q ualit y c h ec ki n g of t he d ata.  
•  All s u bject data rel ati n g t o t he trial will be rec or de d o n electr o nic  C R Fs  u nl ess tra ns mitte d 
electr o nicall y t o N o v o N or dis k or desi g n ee (e. g. l a b orat or y  d ata). T he i n vesti gat or is  
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysi call y or 
electr o nicall y si g ni n g t he C R F.  
•  C orrecti o ns t o t he C R F d ata ma y be ma de b y t he i n vesti gat or or t he i n vesti gat or’s dele gate d 
staff. A n a u dit trail will b e mai ntai ne d i n the C R F a p plicati o n c o ntai ni n g as a mi ni m u m: t he 
ol d a n d t he ne w dat a, i de ntificati o n of t he pers o n e nteri n g t he data, date a n d ti me of t he 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 7
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 8  of 7 4  
 
e ntr y a n d reas o n f or t he c orrecti o n. If c orrecti o ns are ma de b y t he i n v esti gat or’s dele gat e d 
staff aft er t he dat e w hen t he i n vesti gat or si g n e d t he C R F, t he C R F m ust be si g ne d a n d date d 
a gai n b y t he i n vesti gat or.  
•  T he i n vesti gat or m ust e ns ure t hat data is rec or de d i n t he C R F as s o o n as p ossi ble, prefera bl y 
wit hi n 5 w or ki n g da ys after t he visit. O nce dat a has bee n e ntere d, it will be a vaila ble t o 
N o v o N or dis k f or dat a verificati o n a n d vali dati o n p ur p oses.  
T he f oll o wi n g will be pr o vi de d as pa per C R Fs:  
•  Pre g n a nc y f or ms  
T he f oll o wi n g will be pr o vi de d as pa per C R Fs t o be use d w he n access t o t he C R F is re v o ke d or t he 
C R F is te m p oraril y u n a v aila ble: 
•  A E f or ms  
•  Safet y i nf or mati o n f or ms  
•  Tec h nical c o m plai nt f or ms (als o t o be use d t o re p ort c o m plai nts o n trial pr o d uct n ot yet 
all ocate d t o a s u bject)   
1 0. 1. 8. 2   
M o nit ori n g  
•  T he i n vesti gat or m ust per mit trial -relate d m o nit ori n g, a u dits, I R B/I E C re vi e w, a n d 
re g ulat or y a ge nc y i ns pe cti o ns a n d pr o vi de direct access t o s o urce data d oc u me nts ( ori gi nal 
d oc u me nts, data a n d rec or ds). Direct access i ncl u d es per missi o n t o e x a mi ne, a nal ys e, verif y 
a n d re pr o d uce a n y rec or d(s) a n d re p ort(s) t hat are i m p orta nt t o t he e val uati o n of t he trial. If 
t he electr o nic m e dical r ec or d d oes n ot ha v e a visi ble a u dit trail, t he i n vesti gat or m ust 
pr o vi de t he m o nit or wit h si g ne d a n d date d pri nt o uts. I n a d diti o n, t he rele va nt site staff 
s h o ul d be a vaila ble f or disc ussi o ns at m o nit ori n g visits a n d bet wee n m o nit ori n g visits (e. g. 
b y tele p h o n e).   
•  Trial m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat data e ntere d 
i nt o t he C R F b y a ut h oris e d site pers o n nel are acc urate, c o m plete a n d verifia ble fr o m s o urce 
d oc u me n ts; t hat t he safet y a n d ri g hts of s u bjects are bei n g pr otecte d, t o m o nit or dr u g 
acc o u nta bilit y a n d c ollect c o m plete d pa per C R F p a ges, if a p plica ble, a n d t h at t he trial is 
bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot o c ol a n d a n y ot her tria l 
a gree m e nts, I C H G C P, a n d all a p plica ble re g ulat or y re q uire m e nts.  
•  M o nit ori n g will be c o n d ucte d usi n g a ris k -bas e d a p pr oac h i n cl u di n g ris k assess me nt, 
m o nit ori n g pla ns, ce ntr alise d m o nit ori n g (re m ote assess me nt of data b y N o v o N or dis k) a n d 
visits t o sites.   
•  M o nit ors will re vie w t he s u bject’s me dical rec or ds a n d ot her s o urce data,  e. g. t he diaries  t o 
e ns ure c o nsiste n c y a n d/ or i de ntif y o missi o ns c o m pare d t o t he C R F.   
1 0. 1. 8. 3   
Pr ot oc ol c o m pli a nce  
De viati o ns fr o m t he pr ot oc ol s h o ul d be a v oi de d. If de viati o ns d o occ ur, t h e i n vesti gat or m ust 
i nf or m t he m o nit or wit h o ut dela y a n d t he i m plicati o ns of t he de viati o n m ust be re vie we d a n d 
disc usse d.  
De viati o ns m ust be d oc u me nte d a n d e x plai ne d i n a pr ot oc ol de viati o n b y st ati n g t he reas o n, d ate, 
a n d t he acti o n(s) t a ke n. S o me de via ti o ns, f or w hic h c orrecti o ns are n ot p ossi ble, ca n be 
ac k n o wle d ge d a n d c o nfir me d via e dit c hec ks i n t he C R F or via listi n gs fr o m t he trial data base.   
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 8
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 9  of 7 4  
 
1 0. 1. 9   
S o urce d oc u me nts  
•  All data e ntere d i n t he e C R F m ust be verifia ble i n s o urce d oc u m e ntati o n ot her t ha n t he C R F . 
•  C G M data is c o nsi dere d i nter me diate dat a u ntil it has bee n tra nsferre d t o t h e ser vice 
pr o vi der’s dat a base. C G M data tra nsferre d t o t his data base will be c o nsi dere d s o urce data. 
After dat a base l oc k, site s pecific C G M data will be pr o vi de d t o sites f or sit e arc hi v al. 
•  T he ori gi nal of t he c o m pl ete d diaries m ust n ot be re m o ve d fr o m t he site, u nless t he y f or m 
part of t he C R F a n d a c o p y is ke pt at t he site.  
•  S o urce d oc u me nts pr o vi d e e vi de nce f or t h e e xiste nce of t he s u bject a n d s u bsta ntiate t he 
i nte grit y of t he d ata c ollecte d. S o urce d o c u me nts are file d at t he site.  
•  Data re p orte d o n t he pa p er C R F or e nt ere d i n t he e C R F t hat are tra nscri be d fr o m s o urce 
d oc u me nts m ust be c o nsiste nt wit h t he s o urce d oc u me nts, or t he discre p a ncies m ust be 
e x plai ne d. T he i n vesti gat o r ma y n ee d t o re q uest pr e vi o us me dical rec or ds or tra nsfer 
rec or ds. Als o, c urre nt me dical rec or ds m ust be a vaila ble.  
•  It m ust be p ossi ble t o verif y s u bject’s me dical hist or y i n s o urce d o c u me nts, s uc h as s u bject’s 
me dical rec or d.  
•  T he i n vesti gat or m ust d oc u m e nt a n y atte m pt t o o btai n e xter nal me dical i nf or mati o n b y 
n oti n g t he date(s) w he n i nf or mati o n was re q ueste d, a n d w h o was c o ntacte d.  
•  Defi niti o n of w hat c o nstit utes s o urce data ca n b e f o u n d i n a s o urce d o c u me nt a gree me nt at 
eac h site. T here will o nl y be o ne s o urce d oc u me nt defi ne d at a n y ti me f or a n y dat a ele me nt. 
1 0. 1. 1 0   
Rete nti o n of cli nic al tri al d oc u me nt ati o n  
•  Rec or ds a n d d o c u me nts, i ncl u di n g si g n e d i nf or me d c o nse nt f or ms, pertai ni n g t o t he c o n d u ct 
of t his trial m ust be retai ne d b y t h e i n vesti gat or f or 1 5 years after e n d of tri al u nless l ocal 
re g ulati o ns or i nstit uti o nal p olicies re q uire a l o n ger ret e nti o n peri o d. N o rec or ds ma y be 
destr o ye d d uri n g t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of N o v o N or dis k. N o 
rec or ds ma y b e tra nsferre d t o a n ot her l ocati o n or part y wit h o ut writte n n otificati o n t o N o v o 
N or dis k.   
•  T he i n vesti gat or m ust be a ble t o access his/ her trial d oc u me nts wit h o ut i n v ol vi n g N o v o 
N or dis k i n a n y wa y. If a p plica ble, electr o nic C R F (e C R F) a n d ot h er s u bject data will be 
pr o vi de d i n a n electr o ni c rea da bl e f or mat t o t he i n vesti gat or bef ore access is re v o ke d t o t he 
s yste ms a n d/ or electr o nic de vices s u p plie d b y N o v o N or dis k. Site-s pecific C R Fs a n d ot her 
s u bject data (i n a n electr o nic rea d a ble f or mat or as pa per c o pi es or pri nts) m ust be retai ne d 
b y t he site. A c o p y of all data will be st ore d b y N o v o N or dis k. 
•  S u bject’s me dical rec or ds m ust be ke pt f or t he ma xi m u m peri o d per mitte d b y t he h os pital, 
i nstit uti o n or pri vate practice. 
1 0. 1. 1 1   
Tri al a n d site cl os ure  
N o v o N or dis k reser ves t he ri g ht t o cl os e t he site or ter mi nate t he trial at a n y ti me f or a n y reas o n at 
t he s ole discreti o n of N o v o N or dis k. If t he trial is s us pe n de d or ter mi nat e d, t he i n vesti gat or m ust 
i nf or m t he s u bjects pr o m ptl y a n d e ns ure a p pr o priate t hera p y a n d f oll o w-u p. T he i n vesti gat or a n d/ or 
N o v o  N or dis k m ust als o pr o m ptl y i nf or m t he re g ulat or y a ut h orities a n d I R Bs/I E Cs a n d pr o vi de a 
detaile d writte n e x pla nati o n.  
Sites will be cl ose d u p o n trial c o m pleti o n. A site is c o nsi dere d cl os e d w he n all re q uire d d o c u me nts 
a n d trial s u p plies ha ve bee n c ollect e d a n d a site cl os ure visit has bee n perf or me d.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
4 9
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 0  of 7 4  
 
T he i n vesti gat or ma y i nitiate site cl os ure at a n y ti me, pr o vi de d t here is reas o na ble ca us e a n d 
s ufficie nt n otice is gi ve n i n a d va nce of t he i nte n de d ter mi nati o n. 
Reas o ns f or t he earl y cl os ure of a site b y N o v o N or dis k or i n vesti gat or m a y i ncl u de b ut are n ot 
li mite d t o: 
•  fail ure of t he i n v esti gat or t o c o m pl y wit h t he pr ot oc ol, t he re q uire me nts of t he I R B/I E C or 
l ocal healt h a ut h orities, N o v o N or dis k pr oce d ures or G C P g ui deli nes 
•  i na de q uate recr uit me nt of s u bjects b y t he i n vesti gat or  
•  disc o nti n uati o n of f urt her trial pr o d uct de vel o p me nt.  
1 0. 1. 1 2   
Res p o nsi bilities  
T he i n vesti gat or is acc o u nta ble f or t he c o n d uct of t he trial at his/ her site a n d m ust e ns ure a de q u ate 
s u per visi o n of t he c o n d u ct of t he trial at t he site. If a n y tas ks are dele gate d, t he i n vesti gat or m ust 
mai ntai n a l o g of a p pr o priatel y q u alifie d pers o ns t o w h o m he/s he has dele gate d s pecifi e d trial -
relate d d uties. T he i n v esti gat or m ust e ns ure t hat t h ere is a de q uate a n d d oc u me nte d trai ni n g f or all 
staff partici p ati n g i n t he c o n d uct of t he trial. It is t he i n vesti gat or’s res p o nsi bilit y t o s u per vise t he 
c o n d uct of t he trial a n d t o pr otect t he ri g hts, safet y, a n d well -bei n g of t he s u bjects.   
A q ualifie d p h ysicia n, w h o is a n i n vesti gat or or a s u b i n vesti gat or f or t he trial , m ust be res p o nsi ble 
f or all trial-relate d me dical decisi o ns.  
T he i n vesti gat or is res p o nsi ble f or fili n g esse ntial d oc u me nts (i.e. t h ose d oc u me nts w hic h 
i n di vi d uall y a n d c ollecti v el y p er mit e val uati o n of t he c o n d uct of a trial a n d t he q ualit y of t he data 
pr o d uce d) i n t he i n v esti gat or trial master file. T he d oc u me nts, i ncl u di n g t he s u bject i de ntificati o n 
c o de list m ust be ke pt i n a sec ure l oc ke d facilit y s o t hat n o u na ut h orize d pers o ns ca n get access t o 
t he data.  
T he i n vesti gat or will ta ke all necessar y t ec h nical a n d or ga nisati o nal safet y meas ures t o pre ve nt 
acci de nt al or wr o n gf ul d estr ucti o n, l oss or deteri orati o n of data. T he i n vesti gat or will pre ve nt a n y 
u na ut h orise d access t o data or a n y ot her pr ocessi n g of data a gai nst a p plica ble la w. T his als o 
i ncl u des e ns uri n g t hat n o i n direct s hari n g of user cre de ntials f or I T s yste ms use d i n t his st u d y ta kes 
place (e. g., b y n ot s hari n g I T e q ui p me nt wit h ot hers i n a wa y w here us er cre de ntials ha ve t he 
p ossi bilit y of bei n g s h are d).  T he i n vesti gat or m ust be a ble t o pr o vi de t he n ecessar y i nf or mati o n or 
ot her wise de m o nstrat e t o N o v o N or dis k t hat s uc h tec h nical a n d or ga nisati o nal safet y meas ures ha v e 
bee n ta ke n.  
D uri n g a n y peri o d of u na vaila bilit y, t he i n vesti gat or m ust dele gate res p o nsi bilit y f or me dical care of 
s u bjects t o a s pecific q u alifie d p h ysicia n w h o will be rea dil y a v aila ble t o s u bjects d uri n g t h at ti me. 
If t he i n vesti gat or is n o l o n ger a ble t o f ulfil t he r ole as i n vesti gat or (e. g. if he/s he m o ves or retires), 
a ne w i n vesti gat or will b e a p p oi nte d i n c o ns ultati o n wit h N o v o N or dis k.   
T he i n vesti gat or a n d ot her site pers o n nel m ust ha ve s ufficie nt E n glis h s kills acc or di n g t o t heir 
assi g ne d t as k(s).  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
5 0
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 1  of 7 4  
 
1 0. 1. 1 3   
I n de m nit y st ate me nt  
N o v o N or dis k carries pr o d uct lia bilit y f or its pr o d ucts, a n d lia bilit y as ass u me d u n der t he s pecial 
la ws, acts a n d/ or g ui deli n es f or c o n d u cti n g cli nical trials i n a n y c o u ntr y, u nless ot hers ha ve s h o w n 
ne gli ge n ce.   
N o v o N or dis k ass u mes n o lia bilit y i n t he e v e nt of ne gli ge n ce or a n y ot her li a bilit y of t he sites or 
i n vesti gat ors c o n d u cti n g t he trial or b y pers o ns f or w h o m t he sai d site or i n vesti gat or are 
res p o nsi ble.  
1 0. 1. 1 4   
P u blic ati o n p olic y  
T he i nf or mati o n o btai ne d d uri n g t he c o n d uct of t his trial is c o nsi dere d c o nfi de ntial a n d ma y be use d 
b y or o n b e half of N o v o N or dis k f or re g ulat or y p ur p oses as well as f or t he ge n eral d e vel o p me nt of 
t he trial pr o d uct. All i nf or mati o n s u p plie d b y N o v o N or dis k i n c o n necti o n wit h t his trial s hall 
re mai n t he s ole pr o p ert y of N o v o N or dis k a n d is t o be c o nsi dere d c o nfi de ntial i nf or mati o n. 
N o c o nfi de ntial i nf or mati o n s hall be discl o se d t o ot hers wit h o ut pri or writte n c o nse nt fr o m N o v o 
N or dis k. S uc h i nf or mati o n s hall n ot be use d e x ce pt i n t he perf or ma n ce of t his trial.  
T he i nf or mati o n o btai ne d d uri n g t his trial ma y be ma de a vaila ble t o ot her i n vesti gat ors w h o are 
c o n d ucti n g ot h er cli n ical trials wit h t he trial pr o d uct, if dee me d necess ar y b y N o v o N or dis k. 
Pr o vi de d t hat certai n c o n diti o ns are f ulfille d, N o v o N or dis k ma y gra nt access t o i nf or mati o n 
o btai ne d d uri n g t his trial t o researc hers w h o re q uire access f or researc h pr ojects st u d yi n g t he sa m e 
disease a n d/ or tri al pr o d u ct st u die d i n t his trial.  
N o v o N or dis k ma y p u blis h o n its cli nical trials we bsite a re dacte d C T R f or t his trial.  
O ne i n vesti gat or will be a p p oi nte d b y N o v o N or dis k t o re vie w a n d si g n t he C T R (si g nat or y 
i n vesti gat or) o n b e half of all partici pati n g i n v esti gat ors.  
1 0. 1. 1 4. 1   
C o m m u nic ati o n of res ults  
N o v o N or dis k c o m mits t o c o m m u nicate a n d discl ose res ults of trials re gar dless of o utc o me. 
Discl os ure i ncl u des p u bli cati o n of a ma n uscri pt i n a peer -re vi e we d s cie ntific j o ur nal, a bstract 
s ub missi o n wit h a p oster or oral pres e ntati o n at a s cie ntific meeti n g or discl os ure b y ot her mea ns.   
T he res ults of t his trial will be s u bject t o p u blic discl os ure o n e xter nal we b sites acc or di n g t o 
i nter nati o nal a n d nati o nal re g ulati o ns. N o v o N or dis k reser ves t he ri g ht t o defer t he release of data 
u ntil s pecifie d milest o nes are reac he d, f or e x a m ple w he n t he C T R is a vaila ble. T his i ncl u des t he 
ri g ht n ot t o release t he res ults of i nteri m a nal yses, beca use t h e rel ease of s uc h i nf or mati o n ma y 
i nfl ue nce t he res ults of t he e ntire trial. 
At t he e n d of t he trial, o n e or m ore sci e ntific p u blicati o ns ma y b e pre pare d c olla b orati vel y b y t he 
i n vesti gat or(s) a n d N o v o N or dis k. N o v o N or dis k reser ves t he ri g ht t o p ost p o ne p u blicati o n a n d/ or 
c o m m u nicati o n f or u p t o 6 0 da ys t o pr otect i ntellect ual pr o pert y.  
I n all cases, t he trial res ults will be re p orte d i n a n o bjecti ve, acc urat e, bala nce d a n d c o m plete 
ma n ner, wit h a disc ussi o n of t he stre n gt hs a n d li mitati o ns. I n t he e v e nt of a n y disa gree me nt o n t he 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
5 1
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 2  of 7 4  
 
c o nte nt of a n y p u blicati o n,  b ot h t he i n vesti gat ors’ a n d N o v o N or dis k o pi ni o ns will be fairl y a n d 
s ufficie ntl y re prese nte d i n t he p u blicati o n. 
1 0. 1. 1 4. 2   
A ut h ors hi p  
N o v o N or dis k will w or k wit h o ne or m ore i n vesti gat or(s) a n d ot h er e x perts w h o ha ve c o ntri b ute d t o 
t he trial c o nce pt or desi g n, ac quisiti o n, a nal ysis or i nter pretati o n of dat a t o re p ort t he res ults i n o ne 
or m ore p u blicati o ns.  
A ut h ors hi p of p u blicati o ns s h o ul d be i n acc or da n ce wit h t he Rec o m me n d ati o ns f or t he C o n d uct, 
Re p orti n g, E diti n g a n d P u blicati o n of Sc h olarl y W or k i n Me dical J o u r nals b y t he I nt er nati o nal 
C o m mittee of Me dical J o ur nal E dit ors. 3 5 
All a ut h ors will be pr o vi de d wit h t he rele va nt statistical ta bles, fi g ures, a n d re p orts nee d e d t o 
e val uate t he pla n n e d p u blicati o n.   
W here re q uire d b y t he j o ur nal, t he i n vesti gat or fr o m eac h site will be na me d i n a n  
ac k n o wle d ge me nt or i n t he s u p ple me ntar y mat erial, as s pecifie d b y t h e j o ur nal.   
1 0. 1. 1 4. 3   
Site -s pecific p u blic ati o n(s) b y i n vesti g at or(s) 
F or a m ultice ntr e cli nical trial, a nal yses bas e d o n si n gle -site d ata us uall y ha ve si g nifica nt statistical 
li mitati o ns a n d fre q ue ntl y d o n ot pr o vi de mea ni n gf ul i nf or m ati o n f or healt hcare pr ofessi o nals or 
s u bjects, a n d t heref ore m a y n ot b e s u p p orte d b y N o v o N or dis k. T h us, N o v o N or dis k ma y d e n y a 
re q uest or as k f or defer m e nt of t he p u blicati o n of i n di vi d ual site res ults u ntil t he primar y ma n uscri pt 
is acce pte d f or p u blicati o n. I n li ne wit h G o o d P u blicati o n Practice, s u c h i n di vi d ual re p orts s h o ul d 
n ot prece d e t he pri mar y ma n uscri pt a n d s h o ul d al wa ys refere nce t h e pri mar y ma n uscri pt of t he trial.  
1 0. 1. 1 4. 4   
I n vesti g at or access t o d at a a n d re vie w of res ults 
As o w ner of t h e trial data base, N o v o N or dis k h as t he discreti o n t o deter mi n e w h o will ha ve access 
t o t he data base. 
I n di vi d ual i n vesti gat ors will ha ve t heir o w n researc h s u bjects’ d ata a n d will be pr o vi de d wit h t he 
ra n d o misati o n c o de after res ults are a vaila ble.  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
5 2
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 3  of 7 4  
 
1 0. 2   
A p pe n di x 2: Cli nic al l a b or at or y tests  
•  T he tests detaile d i n Ta bl e  1 0 -1  a n d Ta ble  1 0 -2  will be perf or me d b y t h e ce ntral or s pecial 
la b orat or y. 
•  A d diti o nal tests ma y be p erf or me d at a n y ti me d uri n g t he trial as deter mi ne d necessar y b y 
t he i n vesti gat or or re q uir e d b y l o cal re g ul ati o ns. O nl y la b orat or y sa m ples s pecifie d i n t he 
pr ot oc ol s h o ul d be se nt t o t he ce ntral la b orat or y f or a nal ysis; if a d diti o nal la b orat or y 
sam pli n g is nee d e d, e. g. t o f oll o w u p o n A Es, t his m ust be d o ne at a l ocal la b orat or y.  
•  T he ce ntr al la b orat or y will c o m m u nicate t o t he i n vesti gat or a b n or mal val u es of para met ers 
n ot re q ueste d i n t he pr ot o c ol b ut i de ntifie d b y t he l a b orat or y e q ui p me nt a n d/ or t heir 
pr ocesses acc or di n g t o t heir la b S O Ps. T hese data will n ot be tra nsferre d t o t he trial 
data base. T h e i n vesti gat or s h o ul d re vie w s uc h v al ues f or A Es a n d re p ort t hese acc or di n g t o 
t his pr ot oc ol. 
•  T he i n vesti gat or m ust re vie w all la b orat or y res ults f or c o nc o mita nt ill nesses a n d A Es.  
•  F or hae mat ol o g y s a m ples ( differe ntial c o u nt) w here t he test res ult is n ot n or mal, t he n a part 
of t he sa m ple ma y be k e pt f or u p t o t w o years or acc or di n g t o l ocal re g ulati o ns.   
•  Res ult s of p har mac o ki netics , Le pti n a n d S ol u ble le p ti n rece pt or will n ot be s hare d  wit h site . 
•  O utc o me of h y perse nsiti vit y  tests will be c o m m u ni cate d t o site. Res ults of tr y ptase, t otal 
i m m u n o gl o b uli n E (I g E), a nti-ca grili nti de I g E a n d  a nti-se ma gl uti de I g E will n ot be s hare d  
wit h site .  
•  La b orat or y s a m ples will be destr o ye d n o lat er t ha n at fi nalisati o n of t he C T R e x ce pt f or 
sa m ples descri bed  i n S ecti o n 1 0. 6 .  
T a ble  1 0 -1  
Pr ot oc ol -re q uire d effic ac y l a b or at or y assess me nts  
L a b or at or y assess me nts   
P ar a meters  
Visits  
Gl uc ose meta b olis m  
•  H b A 1 c 
1, 2, 4, 6, 8, 1 2, 1 4, 1 6  
•  Fasti n g plas ma gl uc ose 1 
2, 4, 6, 8, 1 2, 1 6  
•  Fasti n g Ser u m I ns uli n  
•  C -P e pti de  
•  Pr oi ns uli n  
•  Gl uca g o n  
2, 6, 1 2, 1 6  
Li pi ds  
•  C h olester ol  
•  Hi g h de nsit y li p o pr otei n ( H D L) c h olester ol  
•  L o w de nsit y li p o pr otei n ( L D L) c h olester ol  
•  Ver y -l o w-de nsit y li p o pr otei n ( V L D L) 
c h olester ol  
•  Tri gl yceri des  
2, 6, 1 2, 1 6  
Bi o mar ker  
•  Hi g h se nsiti ve C -reacti ve pr otei n ( hs C R P)  
•  Le pti n  
•  S ol u ble le pti n rece pt or  
2, 6, 1 2, 1 6  
N O T E S:  
1A n F P G res ult ≤3. 9 m m ol/ L ( 7 0 m g/ d L) i n relati o n t o pla n ne d fasti n g visits s h o ul d n ot be re p orte d as a 
h y p o gl ycae mic  e pis o de b ut as a n A E at t he discreti o n of t he i n vesti gat or ( Secti o n 1 0. 3 ). 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
5 3
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 4  of 7 4  
 
T a ble  1 0 -2  
Pr ot oc ol -re q uire d s afet y l a b or at or y assess me nts  
L a b or at or y  assess me nts   
P ar a meters  
Visits  
Hae mat ol o g y  
•  Hae m o gl o bi n  
•  Hae mat ocrit  
•  Er yt hr oc ytes  
•  T hr o m b oc ytes  
•  Le uc oc ytes  
•  Bas o p hils  
•  E osi n o p hils  
•  L y m p h oc ytes  
•  M o n oc ytes  
•  Ne utr o p hils  
1, 4, 6, 8, 1 2, 1 6  
Bi oc he mistr y 1  
•  Ala ni ne A mi n otr a nsferase ( A L T) 3 
•  Al b u mi n  
•  Al b u mi n c orrecte d calci u m  
•  Al kali ne p h os p hatase  
•  As partate A mi n otra nsferase ( A S T) 3 
•  Bilir u bi n  
•  Calci u m  
•  Creati ne ki nase  
•  Creati ni ne  
•  Ga m ma Gl uta m yl Tra nsferase ( G G T)  
•  Ma g nesi u m  
1, 4, 6, 8, 1 2, 1 6  
•  P otassi u m  
•  S o di u m  
1, 2, 4, 6, 8, 1 2, 1 6, 1 7  
H or m o nes  
•  Al d oster o ne   
•  Plas ma re ni n acti vit y  
•  Al d oster o ne -t o-re ni n acti vit y rati o 
1, 2, 4, 6, 8, 1 2, 1 6,  1 7  
•  T h yr oi d sti m ulati n g h or m o ne ( T S H)  
•  F ol licle-sti m ulati n g h or m o ne ( F S H) (fe male 
s u bj ects o nl y) 4 
1  
Pre g na nc y T esti n g  
•  Hi g hl y se nsiti ve uri ne h u ma n c h ori o nic 
g o na d otr o pi n ( h C G) pre g na nc y test (o nl y 
p ost me n o pa usal fe male s u bj ects w h o ha ve 
st o p pe d me nstr uati n g wit hi n t he last 5 years )2 
1, 2, 4, 6, 8, 1 0, 1 2, 1 4, 1 6, 1 7  
P har mac o ki netics  
•  Se ma gl uti de plas ma c o nce ntrati o n  
•  Ca grili nti de plas ma c o nce ntrati o n  
4, 6, 1 2, 1 6,  
Ot her tests  
•  e G F R calc ulate d b y t he ce ntral la b orat or y 
base d o n t he creati ni ne val ue usi n g t he C K D -
E PI e q uati o n  
1, 4, 6, 8, 1 2, 1 6  
•  tr y ptase  
•  t otal i m m u n o gl o b uli n E (I g E) a nti b o dies 
•  a nti -ca grili nti de I g E a nti b o dies   
•  a nti -se ma gl uti de I g E a nti b o di es  
O nl y i n case of s yste mic 
h y perse nsiti vit y, see secti o n 8. 3. 7  
N otes:  
1Details of re q uire d acti o ns a n d f oll o w -u p assess me nts f or i ncrease d li ver para meters i ncl u di n g a n y disc o nti n uati o n 
criteria are gi ve n i n Secti o n 1 0. 3  ( H y’s La w) a n d Secti o n 7. 1  
2L ocal uri ne testi n g will be sta n dar d u nless ser u m testi n g  is r e q uire d b y l ocal re g ulati o n or I R B/I E C. A pre g na nc y 
test s h o ul d be perf or me d e ver y 4 wee ks a n d at t he E n d of tri al (after 5 wee ks off treat me nt) (refer t o fl o wc hart, 
Secti o n 1. 2  a n d A p pe n di x 4) . 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
5 4
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 5  of 7 4  
 
3If A L T or A S T > 3 u p per n or mal li mit ( U N L), a d diti o nal bl o o d sa m ple s h o ul d be ta ke n fr o m t he s u bj ect t o a nal yse 
i nter nati o nal n or malise d rati o (I N R) b y ce ntral la b orat or y (e xce pt at scree ni n g visit). Re pe at testi n g of t he a b n or mal 
la b orat or y assess me nts s h o ul d be perf or me d via ce ntral la b orat or y f or t he s u bj ect u ntil a b n or malities ret ur n t o n or mal 
or baseli ne state.  
 4A p plica ble f or p ost me n o pa usal w o me n o nl y t o c o nfir m p ost me n o pa usal stat us (see A p pe n di x 4, Secti o n 1 0. 4 )  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
5 5
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 1  of 7 4  
 
Fi g ure  1 0 -1  Decisi o n tree f or deter mi ni n g t he e ve nt t y pe a n d t he res pecti ve f or ms t o 
c o m plete wit h ass oci ate d t i meli nes 
 
C o ntact details f or S A E re p orti n g ca n be f o u n d i n t he i n vesti gat or tri al master file.  
 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
6 1
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 2  of 7 4  
 
1 0. 4   
A p pe n di x 4: C o ntr ace pti ve g ui d a nce a n d c ollecti o n of pre g n a nc y i nf or m ati o n  
It m ust be rec or de d i n t he e C R F w het h er fe male s u bjects are of c hil d beari n g p ote ntial.  
1 0. 4. 1   
Defi niti o ns  
W o m a n of c hil d be ari n g p ote nti al ( W O C B P)  
A w o ma n is c o nsi dere d fertile f oll o wi n g m e narc h e a n d u ntil bec o mi n g p ost me n o pa usal u nless 
per ma ne ntl y sterile.   
If fertilit y is u nclear (e. g. a me n orr hea i n a d oles ce nts or at hletes), a n d a me nstr ual c ycle ca n n ot be 
c o nfir me d bef ore first d ose of trial treat me nt, a d diti o nal e val uati o n s h o ul d be c o nsi dere d.  
Fe m ales i n t he f oll o wi n g c ate g ori es are n ot c o nsi dere d W O C B P  
1.  Fe mal es wit h o ne or m or e of t he f oll o wi n g:  
•  D oc u me nte d t otal h ysterect o m y  
•  D oc u me nte d bilateral sal pi n gect o m y  
•  D oc u me nte d bilateral o o p h orect o m y  
Fe males wit h per ma ne nt i nfertilit y d ue t o a n alter nate me dical ca use ot her t ha n t he a b o ve (e. g. 
M ülleria n a ge n esis, a n d r o ge n i nse nsiti vit y), i n vesti gat or discreti o n s h o ul d be a p plie d i n deter mi ni n g 
trial e nr ol me nt. 
2.  P ost me n o pa usal fe male:  
•  A p ost me n o pa usal state is defi ne d as a m e n orr h o ea f or 1 2 m o nt hs wit h o ut a n alter nati ve 
me dical ca us e  i n a fe m ale > 4 5 years of a ge. Alter nati ve me dical ca uses f or a me n orr h oea 
i ncl u de, b ut are n ot li mite d t o, h or m o nal c o ntrace pti o n or h or m o nal re place me nt t hera p y.   
•  Fe males ≥ 6 0 years of a ge ca n b e c o nsi dere d p ost me n o pa usal.  
A F S H meas ure me nt ma y be us e d t o c o nfir m p ost me n o pa usal stat u s (see A p pe n di x 2, 
Secti o n  1 0. 2 ).  
Fe males o n h or m o ne re pl ace me nt t hera p y ( H R T ) a n d w h ose me n o pa usal stat us is i n d o u bt are 
c o nsi dere d of c hil d beari n g  p ote ntial a n d are n ot eli gi ble t o partici p ate  i n t his trial.  
N ote: D oc u me ntati o n re gar di n g cate g ories 1 -2  ca n c o me fr o m t he site staff’s re vie w of s u bject’s 
me dical rec or ds, me dical e xa mi nati o n or me dical hist or y i nter vie w.  
1 0. 4. 2   
C o ntr ace pti o n g ui d a nce  
M ale s u bjects  
N o c o ntrace pti o n meas ures are re q uir e d f or mal e s u bjects, as t he ris k of terat o ge nicit y/fet ot o xicit y 
ca use d b y tr a nsfer of ca grili nti de i n se mi nal fl ui d is u nli kel y 2 2.  
Fe m ale s u bjects  
Fe male s u bjects of c hil d beari n g p ote ntial are n ot eli gi ble t o partici p ate . 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
6 2
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 3  of 7 4  
 
Pre g n a nc y testi n g  
•  P ost me n o pa usal fe male s u bjects w h o ha ve st o p pe d me nstr uati n g wit hi n t h e last 5 years  m ust 
ha ve uri ne pre g na n c y tests perf or me d at cli nic visits as o utli ne d i n t he fl o wc hart ( Secti o n 
1. 2 ).  
•  Pre g n a nc y testi n g m ust be perf or me d at h o me  i n a d diti o n t o cli nic visits acc or di n g t o t he 
fl o wc hart a n d h o me-testi n g kits m ust be ha n de d o ut acc or di n g t o fl o wc hart 
(see Sect i o n 1. 2 ). 
•  Pre g n a nc y testi n g m ust be re peate d at a n y ti me d uri n g t he tri al if t he s u bject e x perie nces a 
late or misse d me nstr ual c ycle or if pre g na n c y is ot her wise s us pect e d. Trial pr o d ucts m ust 
be dis c o nti n ue d u ntil a pre g n a nc y test has b ee n c o nfir me d ne gati ve b y t h e i n vesti gat or.  
1 0. 4. 3   
C ollecti o n of pre g n a nc y i nf or m ati o n   
Fe m ale s u bjects w h o bec o me pre g n a nt   
•  I n v esti gat or will c ollect pre g na nc y i nf or mati o n o n a n y fe male s u bj ect w h o bec o mes 
pre g na nt w hile par tici pati n g i n t his trial. 
•  I nf or mati o n will be rec or de d o n t he a p pr o priate f or m a n d s u b mitte d t o N o v o N or dis k wit hi n 
1 4 cale n dar da ys of lear ni n g of a s u bj ect’s pre g na nc y (see Fi g ure  1 0 -2 ). 
•  S u bject will be f oll o we d t o deter mi ne t he o utc o me of t he pre g n a nc y. T he i n vesti gat or will 
c ollect f oll o w -u p i nf or m ati o n o n s u bject a n d ne o n ate w hic h will be f or war de d t o N o v o 
N or dis k wit hi n 1 4 cale n dar da ys. Ge nerall y, f oll o w -u p will n ot be re q uire d f or l o n ger t ha n 1 
m o nt h be y o n d t he deli ver y d ate.  
•  A n y ter mi nati o n of pre g n a nc y will be re p orte d, re gar dless of f o etal stat us ( prese nce or 
a bse nce of a n o malies) or i n dicati o n f or pr oce d ure.  
•  W hile p re g na n c y itself is n ot c o nsi dere d t o be a n A E or S A E, a n y a d v erse e ve nt i n 
c o n necti o n wit h pre g n a n c y or electi ve ter mi nati o n of a pre g n a nc y f or me dical reas o ns will 
be re p ort e d as a n A E or S A E. If rele va nt, c o nsi der a d di n g ‘ gestati o nal’, ‘ pre g n a nc y relate d ’ 
or a si milar ter m w he n re p orti n g t he A E/ S A E.  
•  Pre g n a nc y o utc o me s h o ul d be d oc u me nte d i n t he s u bject’s me dical rec or d. A b n or mal 
pre g na nc y o ut c o me (e. g. s p o nta ne o us a b orti o n, f oetal deat h, still birt h, c o n ge nital a n o malies 
a n d ect o pic pre g na n c y) is c o nsi dere d a n S A E.  I n case of a b n or mal pre g na nc y o ut c o me, 
pater nal i nf or m ati o n s h o ul d be rec or de d i n t he a p pr o priate f or m after o btai ni n g t he 
necessar y si g n e d pater nal i nf or me d c o nse nt.  
•  If t he i n vesti gat or lear ns of a n S A E occ urri n g as a res ult of a p ost -trial pre gna nc y w hic h is 
c o nsi dere d relate d t o t he I M P b y t he i n vesti gat or , t he S A E s h o ul d be re p orte d t o N o v o 
N or dis k as descri be d i n A p pe n di x 3  (Secti o n 1 0. 3 ).  
 
 
 
 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
6 3
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 4  of 7 4  
 
Fi g ure  1 0 -2  Decisi o n tree f or deter mi ni n g t he f or ms t o c o m plete wit h ass oci ate d ti meli nes f or 
pre g n a nc y.  
M at er n al f or m 1 b  
  1 4 cal e n d ar d a ys aft er birt h
M at er n al f or m 1 a
  1 4 cal e n d ar d a ys
Aft er birt h/
t er mi n ati o n 
of pr eg n a nc y
N o a d diti o n al 
acti o n
N or m al o ut c o m e 
M at er n al f or m 2   1 4 cal e n d ar d a ys
P at er n al f or m * 1   1 4 cal e n d ar d a ys
A b n or m al o utc o m e 
Pr eg n a ncy 
v erifi e d
* 1 F urt h er i nf or m ati o n c oll ect e d o n P at er n al f or m f or m al e p art n ers of 
f e mal e s u bj ects r e q uir es si g ni n g of s p e cific i nf or m e d c o ns e nt.
A E/ S AEs i n c o n n ecti o n wit h t h e pr e g n a ncy a n d i n t h e f o et us/ n e w b or n 
s h o ul d f oll o w t h e ti m eli n es i n Fi g ur e 1 0. 1.
Pri or t o 
birt h or 
pr e g n a nc y 
t er mi n ati o n 
F or f e m al e s u bj ects
 
 
A n y fe male s u bject w h o bec o mes pre g na nt w hile partici pati n g i n t he tri al will disc o nti n ue I M P.  
 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
6 4
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or d i s k 
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
Stat us:  
Fi n al  
P a ge:  
6 7  of 7 4  
1 0. 6   
A p pe n di x 6: Rete nti o n of h u m a n bi os a m ples  
T he sa m ples will be pse u d oa n o n y mise d (s o pers o nal  data ca n n o l o n ger be attri b ute d t o a s pecific 
data s u bject wit h o ut t he use of a d diti o nal i nf or mati o n s uc h as a u ni q ue sa m ple I D, visit n u m ber, 
trial i de ntificati o n n u m ber a n d sa m pli n g d ate). C o nfi de ntialit y a n d p ers o nal data pr otecti o n will be 
e ns ure d d u ri n g st or a ge after t he e n d of tri al a n d n o direct i de ntificati o n of t h e s u bject will be st ore d 
t o get her wit h t he sa m ples. 
P ote ntial f urt her a nal ys es of t he sa m ples will n ot ha ve a n y c o nse q ue n ces f or t he s u bject.  
T he bi osa m ples will be st ore d at a ce ntral la b orat or y, at a ce ntral st ora ge facilit y or N o v o N or dis k 
f or u p t o 1 5 years after e n d of trial. O nl y rele va nt N o v o N or dis k, c o ns ulta nts, researc h or ga nis ati o ns 
or la b orat ories w or ki n g f or or c olla b orati n g wit h N o v o N or dis k as well as st ora ge facilit y 
e m pl o yees will be a ble t o access t he st ore d bi osa m ples a n d ass ociate d data. T he bi osa m ples ma y be 
tra nsferre d t o ot her c o u ntries f or a n al ysis a n d will be destr o ye d at t he latest 1 5 years after e n d of 
trial. 
T he f oll o w i n g h u m a n bi osa m ples ma y b e ret ai ne d u ntil mar keti n g a ut h orisati o n a p pr o val: 
Resi d u al ca grili nti de  P K s a m ples  
•
T he resi d ual P K sa m ples  ma y b e retai n e d f or lat er a nal ysis of meta b olites or assa y
vali dati o n p ur p oses  if nee de d.
•
T he resi d ual P K sa m ples ma y b e use d f or h y perse nsiti vit y reacti o n a n al ysis.
Resi d u al h y perse nsiti vit y s a m ples  
•
I n case of a s yste mic h y p erse nsiti vit y reacti o n, t he resi d ual h y perse nsiti vit y sa m ples ( please
refer t o Secti o n 8. 3. 7 ) ma y be retai ne d t o f oll o w-u p o n t he h y p erse nsiti vit y reacti o n. If
dee me d rele va nt b y N o v o N or dis k, rele va nt e x pl orat or y a n al ysis ma y b e perf or me d, e. g.,
hista mi ne release ( bas o p hil acti vati o n ), c o m ple me nt a nal ysis, pric k tests a n d/ or i ntra-der mal
tests.
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
6 7
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or d i s k 
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
Stat us:  
Fi n al  
P a ge:  
6 9  of 7 4  
U p o n o nset o f a h y p o gl ycae mic e pis o de t he s u bject is rec o m me n de d t o meas ure P G e v er y 1 5 
mi n utes u ntil t he P G val ue is ≥3. 9 m m ol/ L ( 7 0 m g/ d L) a n d/ or s y m pt o ms ha ve bee n res ol ve d i n 
acc or da nce wit h c urre nt g ui deli nes. 4 1 
Re peate d P G meas ure me nts a n d/ or s y m pt o ms will b y defa ult be c o nsi d ere d as o ne h y p o gl ycae mi c 
e pis o de u ntil a s uccee di n g P G val ue is ≥ 3. 9 m m ol/ L ( 7 0 m g/ d L) a n d/ or s y m pt o ms ha ve bee n 
res ol ve d a n d s h o ul d be re p orte d as o nl y o ne h y p o gl ycae mic e pis o de. I n case of se veral l o w P G 
val ues wit hi n t he h y p o gl ycae mic e pis o de, t he l o west val ue is t he o ne t ha t will be re p orte d as t he P G 
val ue f or t he h y p o gl ycae mic e pis o de, b ut t he start ti me of t he e pis o de will re mai n as t he ti me f or t he 
first l o w P G val ue a n d/ or s y m pt o m. T he re m ai ni n g val u es will be ke pt as s o urce dat a. 
If t he se verit y of a h y p o gl ycae mic e piso de c ha n ges, o nl y o ne h y p o gl ycae mic e pis o de will be 
re p orte d, reflecti n g t he m ost se vere de gree of h y p o gl ycae mia. 
Re gar di n g t he q uesti o n: “ T o feel better, di d y o u n ee d hel p t o get a s u gar y dri n k, f o o d, or 
me dici ne? ” t he i n vesti gat or m ust i nstr uct t he s u bje cts t o a ns wer “ Yes”, if t he e pis o de was a n e v e nt 
t hat re q uire d assista nce of a n ot her p ers o n t o acti vel y a d mi nister car b o h y drate, gl uca g o n, or ta ke 
ot her c orrecti ve acti o ns. P G c o nce ntrati o ns ma y n ot be a vaila ble d uri n g a n e ve nt, b ut ne ur ol o gical 
rec o ver y foll o wi n g t he ret ur n of P G t o n or mal is c o nsi dere d s uffi cie nt e vi d e nce t hat t he e ve nt was 
i n d uce d b y a l o w P G c o n ce ntrati o n.4 1 
A d diti o nal i nf or mati o n (e. g. d escri pti o n of s y m pt o ms, alle viati o n of s y m pt o ms , seiz ure or c o ma) i n 
relati o n t o se vere h y p o gl ycae mic e pis o des m ust be rec or de d i n t he h y p o gl ycae mic e pis o de e C R F.  
Di ar y re vie w  
At eac h c o ntact t he i n vesti gat or m ust re vie w t he diar y d ata f or c orrect re p orti n g of P G val u es a n d 
h y p o gl ycae mic e pis o des. I n case of i nc o m plete or i nc orrect data i n t he diar y, t he s u bject m ust be 
q uesti o ne d w het her t h ere ha ve bee n a n y se v ere h y p o gl ycae mic e pis o des si n ce t he last visit a n d 
re p ort acc or di n gl y. 
F or l o w P G val ues f or h y p o gl ycae mic e pis o des wit h i nc o m plete re p orti n g i nf or mati o n: 
•
If a h y p o gl ycae mic e pis o de f or m i n t he diar y is n ot c o m plete d b y t h e s u bject wit hi n 7
cale n dar da ys of t he P G meas ure me nt, t he e pis o de s h o ul d be descri be d i n t he me dical
rec or ds a n d re p orte d b y t he i n vesti gat or o n a h y p o gl ycae mic e pis o de e C R F wit h as m uc h
i nf or mati o n as p ossi ble. If t he s u bject di d n ot nee d hel p t o get a s u gar y dri n k, f o o d, or
me dici ne, N o v o N or dis k will o nl y as k f or start dat e d ue t o recall bias .4 2, 4 3
Re -tr ai ni n g of s u bjects 
T he s u bject m ust be re -tr ai ne d i n h o w t o re p ort h y p o gl ycae mic e pis o des if t he i n vesti gat or i de ntifies 
l o w P G val ues n ot re p ort e d as h y p o gl ycae mic e pis o des. T he trai ni n g s h o ul d be d oc u me nte d b y t he 
i n vesti gat or i n t he me dical rec or ds. 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
6 9
 
-
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
Stat us:  
Fi n al  
P a ge:  
7 0  of 7 4  
1 0. 8   
A p pe n di x 8: A b bre vi ati o ns  
A D A   
A merica n Dia betes Ass ociati o n  
A E  
a d verse e ve nt  
A L T  
ala ni ne a mi n otra nsferase  
A S T  
as partate a mi n otra nsferase  
B G  
bl o o d gl uc ose  
B MI  
b o d y mass i n de x  
C G M   
c o nti n u o us gl uc ose m o nit ori n g  
C R F  
case re p ort f or m  
C T R  
cli nical trial re p ort  
D B L  
data b ase l oc k 
D F U  
directi o ns f or use  
D U N   
dis pe nsi n g u nit n u m ber  
E C G  
electr ocar di o gra m  
e C R F   
electr o nic case re p ort f or m  
e G F R   
esti mate d gl o mer ular filtrati o n rate  
F A S  
f ull a nal ysis set 
F D A  
U. S. F o o d a n d Dr u g A d mi nistrati o n  
F D A A A   
F D A A me n d me nts Act  
F P G  
fasti n g plas ma gl uc ose 
F S H  
f ollicle-sti m ulati n g h or m o ne 
GI  
gastr oi ntesti nal  
G L P -1   
gl uca g o n -li ke pe pti de-1  
G C P  
G o o d Cli nical Practice  
H b A 1 c  
gl ycate d hae m o gl o bi n  
H R T  
h or m o ne re place me nt t hera p y  
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n 
I E C 
i n de pe n de nt et hics c o m mittee 
I B 
i n vesti gat or’s br oc h ure 
I M P 
i n vesti gati o nal me dici nal pr o d uct 
I R B 
i nstit uti o nal re vie w b oar d 
I W R S  
i nteracti ve we b res p o nse s yste m 
L D L  
l o w-de nsit y li p o pr otei n  
M M R M   
Mi xe d m o del f or re peate d me as ure me nts  
NI M P   
n o n -i n vesti gati o nal me dical pr o d uct 
O A D   
oral a nti -dia betic  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
7 0
 
-
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1
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C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
Stat us:  
Fi n al  
P a ge:  
7 1  of 7 4  
P C D  
pri mar y c o m pleti o n date  
P G  
plas ma gl uc ose  
P K  
p har mac o ki netics  
s.c.
s u bc uta ne us 
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
S G L T 2   
S o di u m -gl uc ose c o -tra ns p orter-2  
S U S A R   
s us pecte d u ne x pecte d seri o us a d verse reacti o n 
T 2 D  
t y pe 2 dia betes 
T M M   
trial materials ma n ual 
U N L  
u p per n or mal li mit  
W O C B P   
w o ma n of c hil d -beari n g p ote ntial  
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
7 1
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
Stat us:  
Fi n al  
P a ge:  
7 2  of 7 4  
1 1  Refere nces  
1. 
A merica n Di a betes Ass o ciati o n. 2. Classificati o n a n d Dia g n osis of Dia betes:. Dia betes Care.
2 0 1 9; 4 2( S u p pl 1): S 1 3 -S 2 8.
2. 
I nter nati o nal Dia betes Fe derati o n. I D F Dia b etes Atlas, 9t h E diti o n. 2 0 1 9.
3. 
Kieffer TJ, Ha be ner J F. T he gl u ca g o n -li ke p e pti des. E n d ocr Re v. 1 9 9 9; 2 0( 6): 8 7 6-9 1 3.
4. 
M üller T D, Fi na n B, Bl o o m S R, D' Alessi o D, Dr uc ker DJ, Flatt P R , et al. Gl uca g o n -li ke
pe pti de 1 ( G L P -1). M ol Meta b. 2 0 1 9; 3 0: 7 2 -1 3 0.
5. 
B o yl e C N, L utz T A, Le F oll C. A m yli n - Its r ole i n t he h o me ostatic a n d he d o nic c o ntr ol of
eati n g a n d rece nt de vel o p me nts of a m yli n a n al o gs t o treat o besit y. M ol M eta b. 2 0 1 8; 8: 2 0 3 -
1 0.
6 . 
U S Prescri bi n g I nf or mati o n, 2 0 1 6 f or S y mli n ®, N D A 2 1 -3 3 2.
7. 
Y o u n g A, De nar o M. R oles of a m yli n i n dia betes a n d i n re g ulati o n of n utrie nt l oa d.
N utriti o n. 1 9 9 8; 1 4( 6): 5 2 4 -7.
8. 
Gar ber AJ, Ha n dels ma n Y, Gr u n ber ger G, Ei n h or n D, A bra h a ms o n MJ, Barzila y JI, et al.
C o nse ns us State me nt b y t he A merica n Ass ociati o n of Cli nical E n d ocri n ol o gists a n d
A merica n C olle ge of E n d ocri n ol o g y o n t he C o m pre he nsi ve T y p e 2 Dia betes Ma na ge me nt
Al g orit h m - 2 0 2 0 E x ec uti ve S u m mar y. E n d ocr Pract. 2 0 2 0; 2 6( 1): 1 0 7 -3 9.
9. 
C ose nti n o F, G ra nt PJ, A b o ya ns V, Baile y CJ, Ceriell o A, Del ga d o V, et al. 2 0 1 9 E S C
G ui deli nes o n dia betes, pre -dia betes, a n d car di o vasc ular diseas es de vel o pe d i n c olla b orati o n
wit h t he E A S D. E ur Heart J. 2 0 2 0; 4 1( 2): 2 5 5 -3 2 3.
1 0. 
Ta yl or R, Al -Mra b e h A, Sattar N. U n derst a n di n g t he mec ha nis ms of re versal of t y p e 2
dia betes. La n cet Dia bet es E n d ocri n ol. 2 0 1 9; 7( 9): 7 2 6 -3 6.
1 1. 
G u m mess o n A, N y m a n E, K n utss o n M, Kar pef ors M. Effect of wei g ht re d ucti o n o n
gl ycate d hae m o gl o bi n i n wei g ht l oss trials i n patie nts wit h t y p e 2 dia betes.  Dia betes O bes
Meta b. 2 0 1 7; 1 9( 9): 1 2 9 5 -3 0 5.
1 2. 
La u J, Bl oc h P, Sc häffer L, Petterss o n I, S petzler J, K of oe d J, et al. Disc o ver y of t he O nce -
Wee kl y Gl uca g o n -Li ke P e pti de -1 ( G L P -1) A nal o g ue Se ma gl uti de. J Me d C he m.
2 0 1 5; 5 8( 1 8): 7 3 7 0 -8 0.
1 3. 
N o v o N or dis k A/ S. Oze m pic ®  (se ma gl uti de), E U S u m mar y of Pr o d uct C haract eristics
( S m P C). 2 0 1 8.
1 4. 
N o v o N or dis k A/ S. Oze m pic ® (se ma gl uti de), U S Prescri bi n g I nf or mati o n ( PI). Dec 2 0 1 7.
1 5. 
N o v o N or dis k A/ S. C o m pa n y A n n o u nce m e nt:  O nce -wee kl y se ma gl uti de 2. 0 m g
de m o nstrates s u peri or re d ucti o n i n H b A 1c vs o nce -wee kl y s e ma gl uti de 1. 0 m g i n pe o ple
wit h t y pe 2 dia betes i n t he S U S T AI N F O R T E trial 2 0 2 0 [cite d 2 0 2 0 1 7 N o ve m ber].
1 6. 
Wil di n g J P H, Batter ha m R L, Cala n na S, Da vies M, Va n Gaal L F, Li n g va y I, et al. O nce -
Wee kl y Se ma gl uti de i n A d ults wit h O ver wei g ht or O besit y. N E n gl J Me d. 2 0 2 1.
1 7. 
Da vies M, F ærc h L, J e p pese n O K, Pa kseres ht A, Pe derse n S D, Perrea ult L, et al.
Se ma gl uti de 2· 4 m g o nce a wee k i n a d ults wit h o ver wei g ht or o besit y, a n d t y pe 2 dia betes
( S T E P 2): a ra n d o mise d, d ou ble -bli n d, d o u ble -d u m m y, place b o -c o ntr olle d, p hase 3 trial.
La n cet. 2 0 2 1; 3 9 7( 1 0 2 7 8): 9 7 1 -8 4.
1 8. 
Ar o da V, A h m a n n A, Cari o u B, C h o w F, Da vies M, J´ o dar E, et al. C o m parati ve efficac y,
safet y, a n d car di o vas c ular o utc o mes wit h o nce-wee kl y s u bc uta ne o us se ma gl uti de i n t he
treat me nt of t y pe 2 dia betes: I nsi g hts fr o m t he S U S T AI N 1– 7 trials. Dia bet es &
Meta b olis m. 2 0 1 8.
1 9. 
L ys e n g -Willia ms o n K A. Gl uca g o n -Li ke Pe pti de -1 Rece pt or A n al o g u es i n T y pe 2 Dia betes:
T heir Use a n d Differe nti al Feat ures. Cli n Dr u g I n ve sti g. 2 0 1 9; 3 9( 8): 8 0 5-1 9.
2 0. 
Na uc k M A, Mei er JJ. M A N A G E M E N T O F E N D O C RI N E DI S E A S E: Are all G L P -1
a g o nist e q u al i n t he treat me nt of t y pe 2 di a betes? E ur J E n d ocri n ol. 2 0 1 9.
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
7 2
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 3  of 7 4  
 
 
2 1.   
N o v o N or dis k A/ S. I n v esti gat or's  Br oc h ure, Se ma gl uti de s.c. 2. 4 m g f or wei g ht 
ma n a ge me nt, pr ojects N N 9 5 3 6 a n d E X 9 5 3 6 (e diti o n 6). 0 3 Dec 2 0 2 0.  
2 2.   
N o v o N or dis k A/ S. I n v esti gat or Br oc h ure, N N C 0 1 7 4 -0 8 3 3/ Ca grili nti de/ Ca gri Se ma, pr oject 
N N 9 8 3 8 (e diti o n 6). 2 1 Dec 2 0 2 0.  
2 3.   
N o v o N or dis k A/ S. Oze m pic ® (se ma gl uti de), U S prescri bi n g I nf or m ati o n ( PI). Ja n 2 0 2 0.  
2 4.   
B use J B, We xler DJ, Tsa pas A, R ossi n g P, Mi n gr o ne G, Mat hie u C, et al. 2 0 1 9 U p date t o: 
Ma na ge me nt of H y per gl yce mia i n T y pe 2 Dia b et es, 2 0 1 8. A C o nse ns us Re p ort b y t h e 
A merica n Di a betes Ass o ciati o n ( A D A) a n d t he E ur o pea n Ass o ciati o n f o r t he St u d y of 
Dia betes ( E A S D). Dia bet es Care. 2 0 2 0; 4 3( 2): 4 8 7 -9 3.  
2 5.   
Da vies MJ, D' Alessi o D A, Fra d ki n J, Ker na n W N, Mat hie u C, Mi n gr o ne G, et al. 
Ma na ge me nt of H y per gl yce mia i n T y pe 2 Dia b et es, 2 0 1 8. A C o nse ns us Re p ort b y t h e 
A merica n Di a betes Ass o ciati o n  ( A D A) a n d t he E ur o pea n Ass o ciati o n f or t he St u d y of 
Dia betes ( E A S D). Dia bet es Care. 2 0 1 8; 4 1( 1 2): 2 6 6 9 -7 0 1.  
2 6.   
Ba n ks P A, B olle n T L, Der ve nis C, G o osze n H G, J o h ns o n C D, Sarr M G, et al. Classificati o n 
of ac ute pa ncreatitis -2 0 1 2: re visi o n of t he Atla nta class ificati o n a n d defi niti o ns b y 
i nter nati o nal c o nse ns us. G ut. 2 0 1 3; 6 2( 1): 1 0 2 -1 1.  
2 7.   
Da vies MJ, D’ Alessi o D A, Fra d ki n J, Ker na n W N, Mat hie u C, Mi n gr o ne G, et al. 
Ma na ge me nt of h y p er gl ycae mia i n t y pe 2 dia betes, 2 0 1 8. A c o nse ns us re p ort b y t he 
A merica n Di a bete s Ass o ciati o n ( A D A) a n d t he E ur o pea n Ass o ciati o n f or t he St u d y of 
Dia betes ( E A S D). Dia bet ol o gia. 2 0 1 8; 6 1( 1 2): 2 4 6 1 -9 8.  
2 8.   
W orl d Me dical Ass ociati o n. W M A Declarati o n of Helsi n ki - Et hical Pri nci ples f or Me dical 
Researc h I n v ol vi n g H u ma n S u bjects. Last a me n de d b y t he 6 4t h W M A Ge n eral Asse m bl y, 
F ortaleza, Brazil. Oct o ber 2 0 1 3.  
2 9.   
I C H Har m o nise d Tri p artite G ui deli ne. G ui deli ne f or G o o d Cli nical Practice E 6( R 2), Ste p 4 
versi o n. 0 9 N o v 2 0 1 6.  
3 0.   
De A n gelis C, Draze n J M, Frizelle F A, Ha u g C, H oe y J, H ort o n R, et a l. Cli nical trial 
re gistrati o n: a state me nt fr o m t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors. N 
E n gl J Me d. 2 0 0 4; 3 5 1( 1 2): 1 2 5 0 -1.  
3 1.   
U. S. De part me nt of Healt h a n d H u ma n Ser vices, F o o d a n d Dr u g A d mi nistrati o n. F o o d a n d 
Dr u g A d mi nistrati o n A me n d me nts Act of 2 0 0 7 as a me n de d b y t he Fi nal R ule " Cli nical 
Trials Re gistrati o n a n d Res ults I nf or mati o n S u b missi o n". 2 1 Se pte m ber 2 0 1 6.  
3 2.   
T he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n C o u ncil. Directi ve 2 0 0 1/ 2 0/ E C 
of t he E ur o pea n Parlia me nt a n d of t he C o u ncil of 4 A pril 2 0 0 1 o n t he a p pr o xi mati o n of t he 
la ws, re g ulati o ns a n d a d mi nistrati ve pr o visi o ns of t he me m ber states relati n g t o t he 
i m ple me ntati o n of g o o d cli nical practice i n t he c o n d uct of cli nical trials o n me dici nal 
pr o d ucts f or h u ma n us e. 2 0 0 1 . 
3 3.   
T he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n C o u ncil. Re g ulati o n ( E C) N o 
7 2 6/ 2 0 0 4 of t he E ur o pea n Parlia me nt a n d of t he C o u ncil of 3 1 Marc h 2 0 0 4 la yi n g d o w n 
C o m m u nit y pr oce d ures f or t he a ut h orisati o n a n d s u per visi o n of me dici nal pr o d ucts f or 
h u ma n a n d veteri n ar y us e a n d esta blis hi n g a E ur o pea n Me dici nes A ge nc y, article 5 7. 3 0 
A pril 2 0 0 4.  
3 4.   
T he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n C o u ncil. Re g ulati o n ( E C) N o 
1 9 0 1/ 2 0 0 6 of t he E ur o pea n Parlia me nt a n d of t h e C o u ncil of 1 2 Dece m b er 2 0 0 6 o n 
me dici nal pr o d ucts f or p ae diatric use a n d a me n di n g Re g ulati o n ( E E C) N o 1 7 6 8/ 9 2, 
Directi ve 2 0 0 1/ 2 0/ E C, Directi ve 2 0 0 1/ 8 3/ E C a n d Re g ulati o n ( E C) N o 7 2 6/ 2 0 0 4, article 4 1. 
Official J o ur nal of t he E ur o pea n C o m m u nities. 2 7 Dec 2 0 0 6.  
3 5.   
I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors. Rec o m me n dati o ns f or t he C o n d uct, 
Re p orti n g, E diti n g a n d P u blicati o n of Sc h olarl y W or k i n Me dical J o ur nals; c urre nt versi o n 
a vaila ble at w w w.ic mje. or g . 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
7 3
 
-
 |
1
 |
C O N FI D E N TI A L

Pr ot oc ol  
 
Date:  
1 6 J u ne 2 0 2 1  N o v o N or di s k  
Trial I D: N N 9 8 3 8 -4 8 6 2  
V ersi o n:  
2. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 4  of 7 4  
 
 
3 6.   
I nter nati o nal H y p o gl ycae mia St u d y Gr o u p. Gl uc os e C o nce ntrati o ns of Less T ha n 3. 0 
m m ol/ L ( 5 4 m g/ d L) S h o ul d Be Re p orte d i n Cli nical Trials: A J oi nt P ositi o n State me nt of 
t he A merica n Dia betes Ass ociati o n a n d t he E ur o pea n Ass ociati o n f or t he St u d y of Di a betes. 
Dia betes Care. 2 0 1 7; 4 0( 1): 1 5 5 -7.  
3 7.   
A merica n Di a betes Ass o c iati o n. 6. Gl yce mic Tar gets: Sta n dar ds of Me dical Care i n 
Dia betes -2 0 1 8. Di a betes Care. 2 0 1 8; 4 1( S u p pl 1): S 5 5 -S 6 4.  
3 8.   
A bra ha m M B, J o nes T W, Nara nj o D, Kar ges B, O d u w ole A, Ta usc h m a n n M, et al. I S P A D 
Cli nical Practice C o nse ns us G ui deli nes 2 0 1 8: Assess me nt a n d ma na ge me nt of 
h y p o gl yce mia i n c hil dre n a n d a d olesce nts wit h dia betes. Pe diatr Dia b etes. 2 0 1 8; 1 9 S u p pl 
2 7: 1 7 8 -9 2.  
3 9.   
A gi ostrati d o u G, A n h alt H, Ball D, Bl o n de L, G o ur gari E, Harri ma n K N, et al. 
Sta n dar dizi n g Cli nicall y Mea ni n gf ul O utc o me Meas ures Be y o n d  H b A 1 c f or T y p e 1 
Dia betes: A C o nse ns us Re p ort of t he A merica n Ass ociati o n of Cli nical E n d ocri n ol o gists, 
t he A merica n Ass ociati o n of Dia betes E d ucat ors, t he A merica n Dia betes Ass ociati o n, t he 
E n d ocri ne S ociet y, J D R F I nter nati o nal, T he Le o na M. a n d Harr y B.  Hel msle y C harita ble 
Tr ust, t he Pe diatric E n d o cri ne S ociet y, a n d t he T 1 D E x c ha n ge. Dia betes C are. 
2 0 1 7; 4 0( 1 2): 1 6 2 2 -3 0.  
4 0.   
Da n ne T, Ni mri R, Batteli n o T, Ber ge nstal R M, Cl ose K L, De Vries J H, et al. I nter nati o nal 
C o nse ns us o n Use of C o nti n u o us Gl uc ose M o nit ori n g. Dia betes Care. 2 0 1 7; 4 0( 1 2): 1 6 3 1 -4 0.  
4 1.   
Sea q uist E R, A n ders o n J, C hil ds B, Cr yer P, Da g o g o -J ac k S, Fis h L, et al. H y p o gl yce mia 
a n d dia betes: a re p ort of a w or k gr o u p of t he A merica n Dia bet es Ass ociati o n a n d t he 
E n d ocri ne S ociet y. Dia b etes Care. 2 0 1 3; 3 6( 5): 1 3 8 4 -9 5.  
4 2.   
U S F o o d a n d Dr u g A d mi nistrati o n. G ui da nce f or I n d ustr y. Patie nt -Re p orte d O utc o me 
Meas ures: Us e i n Me dical Pr o d uct De vel o p me nt t o S u p p ort La b eli n g Clai ms. Dece m ber 
2 0 0 9.  
4 3.   
St ull D E, Lei d y N K, Paras ura ma n B, C hassa n y O. O pti mal reca ll peri o ds f or patie nt-
re p orte d o utc o m es: c hall e n ges a n d p ote ntial s ol uti o ns. C urr Me d Res O pi n. 2 0 0 9; 2 5( 4): 9 2 9-
4 2.  
 
  Pr ot oc ol  4 8 6 2 Pr ot oc ol V 2 0
N N 9 8 3 8- 4 8 6 2
N N 9 8 3 8
0
 |
V V- T M F- 4 5 3 5 0 0 0
7 4
 of
7 4
 
-
 |
1
 |
C O N FI D E N TI A L

1 6. 1. 0 1  
Pr ot oc ol  Att ac h me nt  
Pr ot oc ol A ttac h me nt I is l ocate d i n t he Trial Mast er File. 
If a p plica bl e, Pr ot oc ol Attac h me nt II is als o l ocate d i n t he Trial Master File. 
C o nte nt: Gl o bal ke y staff a n d C o u ntr y k e y staff.  
Date:
N o v o N or di s k
Versi o n:
Stat us:
Ca gri Se ma
Trial I D: N N 9 8 3 8 4 8 6 2
Cli nical Trial Re p ort
A p pe n di x 1 6. 1. 1
0 1 N o ve m ber 2 0 2 2
1. 0
Fi nal
C O N FI D E N TI A L