Clinical trial NCT01930188: Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin and/or TZD in Subjects With Type 2 Diabetes
Official title: Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin and/or TZD in Subjects With Type 2 Diabetes (SUSTAIN™ 2 - vs. DPP-4 Inhibitor)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2013-08-28
Enrollment: 1231
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Africa, Asia, Europe and South America. The aim of the trial is to evaluate efficacy and safety of semaglutide once-weekly versus sitagliptin once-daily as add-on to metformin and/or TZD (thiazolidinedione) in subjects with type 2 diabetes.


Eligibility criteria: Inclusion Criteria: - Japan: Age minimum 20 years - Subjects diagnosed with type 2 diabetes and on stable treatment in a period of 90 days prior to screening with either metformin above or equal to 1500 mg (or maximum tolerated dose), pioglitazone above or equal to 30 mg (or maximum tolerated dose), rosiglitazone above or equal to 4 mg (or maximum tolerated dose) or a combination of either metformin/pioglitazone or metformin/rosiglitazone (doses as for individual therapies). Stable is defined as unchanged medication and unchanged dose - HbA1c 7.0 - 10.5 % (53 - 91 mmol/mol) (both inclusive) Exclusion Criteria: - Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using an adequate contraceptive method throughout the trial including the 5 weeks follow-up period (adequate contraceptive measures as required by local law or practice) - Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (below or equal to 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value above or equal to 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 per modification of diet in renal disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association (NYHA) class IV

Primary outcomes:
measure: Change in HbA1c (Glycosylated Haemoglobin) From Baseline
timeFrame: Week 0, week 56
Secondary outcomes:
measure: Change in Body Weight From Baseline
timeFrame: Week 0, week 56
measure: Change in Fasting Plasma Glucose (FPG) From Baseline
timeFrame: Week 0, week 56
measure: Change in Systolic and Diastolic Blood Pressure From Baseline
timeFrame: Week 0, week 56
measure: Change in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) From Baseline
timeFrame: Week 0, week 56
measure: Subjects Who Achieved HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target (Yes/no)
timeFrame: After 56 weeks treatment
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Mar del Plata
country: Argentina
facility: Novo Nordisk Investigational Site
city: Burgas
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Haskovo
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Petrich
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Ruse
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sliven
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Smolyan
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Stara Zagora
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Vratsa
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Chrudim
country: Czechia
facility: Novo Nordisk Investigational Site
city: Ostrava
country: Czechia
facility: Novo Nordisk Investigational Site
city: Plzen
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha 4- Chodov
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha 5
country: Czechia
facility: Novo Nordisk Investigational Site
city: Shatin, New Territories
country: Hong Kong
facility: Novo Nordisk Investigational Site
city: Budapest
country: Hungary
facility: Novo Nordisk Investigational Site
city: Budapest
country: Hungary
facility: Novo Nordisk Investigational Site
city: Debrecen
country: Hungary
facility: Novo Nordisk Investigational Site
city: Szeged
country: Hungary
facility: Novo Nordisk Investigational Site
city: Szombathely
country: Hungary
facility: Novo Nordisk Investigational Site
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Novo Nordisk Investigational Site
state: Gujarat
city: Bangalore
country: India
facility: Novo Nordisk Investigational Site
state: Karnataka
city: Bangalore
country: India
facility: Novo Nordisk Investigational Site
state: Karnataka
city: Kochi
country: India
facility: Novo Nordisk Investigational Site
state: Kerala
city: Kozhikode
country: India
facility: Novo Nordisk Investigational Site
state: Kerala
city: Trivandrum
country: India
facility: Novo Nordisk Investigational Site
state: Kerala
city: Indore
country: India
facility: Novo Nordisk Investigational Site
state: Madhya Pradesh
city: Mumbai
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Bhubaneswar
country: India
facility: Novo Nordisk Investigational Site
state: Orissa
city: Ludhiana
country: India
facility: Novo Nordisk Investigational Site
state: Punjab
city: Jaipur
country: India
facility: Novo Nordisk Investigational Site
state: Rajasthan
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: New Delhi
country: India
facility: Novo Nordisk Investigational Site
city: Asahikawa-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Kashiwara-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Kitakyushu-shi, Fukuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Mitaka-shi, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Mito-shi, Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Miyazaki
country: Japan
facility: Novo Nordisk Investigational Site
city: Okayama-shi, Okayama
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Sapporo-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Pachuca
country: Mexico
facility: Novo Nordisk Investigational Site
state: Hidalgo
city: Guadalajara
country: Mexico
facility: Novo Nordisk Investigational Site
state: Jalisco
city: Monterrey
country: Mexico
facility: Novo Nordisk Investigational Site
state: Nuevo León
city: Aguascalientes
country: Mexico
facility: Novo Nordisk Investigational Site
city: Aguascalientes
country: Mexico
facility: Novo Nordisk Investigational Site
city: Hamar
country: Norway
facility: Novo Nordisk Investigational Site
city: Kløfta
country: Norway
facility: Novo Nordisk Investigational Site
city: Kongsvinger
country: Norway
facility: Novo Nordisk Investigational Site
city: Stavanger
country: Norway
facility: Novo Nordisk Investigational Site
city: Ålesund
country: Norway
facility: Novo Nordisk Investigational Site
city: Almada
country: Portugal
facility: Novo Nordisk Investigational Site
city: Coimbra
country: Portugal
facility: Novo Nordisk Investigational Site
city: Lisboa
country: Portugal
facility: Novo Nordisk Investigational Site
city: Lisboa
country: Portugal
facility: Novo Nordisk Investigational Site
city: Matosinhos
country: Portugal
facility: Novo Nordisk Investigational Site
city: Tomar
country: Portugal
facility: Novo Nordisk Investigational Site
city: Viana do Castelo
country: Portugal
facility: Novo Nordisk Investigational Site
city: Vila Nova de Gaia
country: Portugal
facility: Novo Nordisk Investigational Site
city: Baia Mare
country: Romania
facility: Novo Nordisk Investigational Site
state: Maramures
city: Ploiesti
country: Romania
facility: Novo Nordisk Investigational Site
state: Prahova
city: Brasov
country: Romania
facility: Novo Nordisk Investigational Site
city: Bucharest
country: Romania
facility: Novo Nordisk Investigational Site
city: Bucharest
country: Romania
facility: Novo Nordisk Investigational Site
city: Barnaul
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Samara
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Smolensk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Tomsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Tumen
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Ufa
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Volgograd
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Voronezh
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Yaroslavl
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: East London
country: South Africa
facility: Novo Nordisk Investigational Site
state: Eastern Cape
city: Bloemfontein
country: South Africa
facility: Novo Nordisk Investigational Site
state: Free State
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Krugersdorp
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Almería
country: Spain
facility: Novo Nordisk Investigational Site
city: Centelles (Barcelona)
country: Spain
facility: Novo Nordisk Investigational Site
city: La Coruña
country: Spain
facility: Novo Nordisk Investigational Site
city: La Roca del Vallés
country: Spain
facility: Novo Nordisk Investigational Site
city: Lleida
country: Spain
facility: Novo Nordisk Investigational Site
city: Palma de Mallorca
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Kristianstad
country: Sweden
facility: Novo Nordisk Investigational Site
city: Lund
country: Sweden
facility: Novo Nordisk Investigational Site
city: Malmö
country: Sweden
facility: Novo Nordisk Investigational Site
city: Stockholm
country: Sweden
facility: Novo Nordisk Investigational Site
city: Bangkoknoi, Bangkok
country: Thailand
facility: Novo Nordisk Investigational Site
city: Bangkok
country: Thailand
facility: Novo Nordisk Investigational Site
city: Bangkok
country: Thailand
facility: Novo Nordisk Investigational Site
city: Nakhon Ratchasima
country: Thailand
facility: Novo Nordisk Investigational Site
city: Ankara
country: Turkey
facility: Novo Nordisk Investigational Site
city: Antalya
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Konya
country: Turkey
facility: Novo Nordisk Investigational Site
city: Rize
country: Turkey
facility: Novo Nordisk Investigational Site
city: Trabzon
country: Turkey
facility: Novo Nordisk Investigational Site
city: Çorum
country: Turkey
facility: Novo Nordisk Investigational Site
city: Cherkasy
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Ivano-Frankivsk
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Kyiv
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Odesa
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Vinnytsia
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Zaporizhia
country: Ukraine
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Fonseca VA, Capehorn MS, Garg SK, Jodar Gimeno E, Hansen OH, Holst AG, Nayak G, Seufert J. Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide. J Clin Endocrinol Metab. 2019 Sep 1;104(9):4078-4086. doi: 10.1210/jc.2018-02685.
citation: Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA1C >/=1.0% AND WEIGHT >/=5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13.
citation: Ahrén B, Comas LM, Kumar H, Sargin M, Derving Karsbøl J, Jacobsen SH, Chow F. Efficacy and Safety of Once-weekly Semaglutide vs Sitagliptin as add-on to Metformin and/or Thiazolidinediones After 56 Weeks in Subjects With Type 2 Diabetes (SUSTAIN 2). Oral Presentation 12 Jun 2016 at American Diabetes Association - 76th Annual Scientific Sessions.
citation: Ahrén B, Masmiquel L, Kumar H, Sargin M, Derving Karsbøl J, Jacobsen SH, Chow F. Efficacy and Safety of Once-weekly Semaglutide vs Sitagliptin as add-on to Metformin and/or Thiazolidinediones After 56 Weeks in Subjects With Type 2 Diabetes (SUSTAIN 2). ePoster #767 presented 12 Sep 2016 at European Association for the Study of Diabetes - 52nd Annual Meeting.
citation: Ahren B, Masmiquel L, Kumar H, Sargin M, Karsbol JD, Jacobsen SH, Chow F. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 2017 May;5(5):341-354. doi: 10.1016/S2213-8587(17)30092-X. Epub 2017 Apr 3.
citation: Petri KCC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes. Diabetes Obes Metab. 2018 Sep;20(9):2238-2245. doi: 10.1111/dom.13358. Epub 2018 Jun 15.
citation: Ahren B, Atkin SL, Charpentier G, Warren ML, Wilding JPH, Birch S, Holst AG, Leiter LA. Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2210-2219. doi: 10.1111/dom.13353. Epub 2018 Jun 12.
citation: Sharma R, Wilkinson L, Vrazic H, Popoff E, Lopes S, Kanters S, Druyts E. Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review and network meta-analysis. Curr Med Res Opin. 2018 Sep;34(9):1595-1603. doi: 10.1080/03007995.2018.1476332. Epub 2018 May 29.
citation: DeVries JH, Desouza C, Bellary S, Unger J, Hansen OKH, Zacho J, Woo V. Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. Diabetes Obes Metab. 2018 Oct;20(10):2426-2434. doi: 10.1111/dom.13396. Epub 2018 Jul 9.
citation: Carlsson Petri KC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Semaglutide s.c. Once-Weekly in Type 2 Diabetes: A Population Pharmacokinetic Analysis. Diabetes Ther. 2018 Aug;9(4):1533-1547. doi: 10.1007/s13300-018-0458-5. Epub 2018 Jun 15.
citation: Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jodar E, Mehta R, Woo V, Lingvay I. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019 Oct;45(5):409-418. doi: 10.1016/j.diabet.2018.12.001. Epub 2019 Jan 4.
citation: Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.
citation: Lingvay I, Capehorn MS, Catarig AM, Johansen P, Lawson J, Sandberg A, Shaw R, Paine A. Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis. J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4593-604. doi: 10.1210/clinem/dgaa577.
citation: Capehorn M, Ghani Y, Hindsberger C, Johansen P, Jodar E. Once-Weekly Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2-4 and 10. Diabetes Ther. 2020 May;11(5):1061-1075. doi: 10.1007/s13300-020-00796-z. Epub 2020 Mar 19.
citation: Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.
citation: DeSouza C, Cariou B, Garg S, Lausvig N, Navarria A, Fonseca V. Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials. J Clin Endocrinol Metab. 2020 Feb 1;105(2):dgz072. doi: 10.1210/clinem/dgz072.
citation: Jendle J, Birkenfeld AL, Polonsky WH, Silver R, Uusinarkaus K, Hansen T, Hakan-Bloch J, Tadayon S, Davies MJ. Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials. Diabetes Obes Metab. 2019 Oct;21(10):2315-2326. doi: 10.1111/dom.13816. Epub 2019 Jul 12.