Zynquista

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 
 

 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions.  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zynquista 200 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 200 mg sotagliflozin. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Oval, blue, film-coated tablet printed with “2456” on one side in black ink (tablet length: 14.2 mm, 
tablet width: 8.7 mm). 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Zynquista is indicated as an adjunct to insulin therapy to improve glycaemic control in adults with 
type 1 diabetes mellitus with a Body Mass Index (BMI) ≥ 27 kg/m2, who have failed to achieve 
adequate glycaemic control despite optimal insulin therapy. 
 
 
4.2 Posology and method of administration 
 
Therapy with Zynquista should be initiated and supervised by a physician experienced in the 
management of type 1 diabetes mellitus. 
 
Posology 
 
The recommended dose is 200 mg sotagliflozin once daily before the first meal of the day. After at 
least three months, if additional glycaemic control is needed, in patients tolerating sotagliflozin 
200 mg, the dose may be increased to 400 mg once daily. 
 
Before initiating treatment with sotagliflozin 200 mg and before increasing dose to sotagliflozin 400 
mg: 
 

- Risk factors for diabetic ketoacidosis (DKA) should be assessed and ketone levels should be 
evaluated as normal. If ketones are elevated (blood beta-hydroxybutyrate (BHB) reading is 
greater than 0.6 mmol/L or urine ketones one plus (+)) treatment with sotagliflozin should not 
be initiated nor the dose should be increased to sotagliflozin 400 mg until the ketone levels are 
normal (see sections 4.4). 

- It is recommended that patients obtain several baseline blood or urine ketone levels over one 
to two weeks prior to initiation of sotagliflozin therapy, and, patients should become familiar 
with how their behaviours and circumstances affect their ketone levels. 



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- Patients must be able to perform self-management of the day-to-day aspects of their disease 
including self-monitoring of glucose and ketones.  

- Patients should be informed, in a dedicated education session, on the risk of DKA, how to 
recognize DKA risk factors, signs or symptoms, how and when to monitor ketone levels and 
what actions to take when ketone levels are elevated (see section 4.4). 

- Correction of volume depletion prior to initiation of sotagliflozin is recommended in patients 
with this condition (see section 4.4). 

 
Sotagliflozin must only be administered as an adjunct to insulin. In order to avoid hypoglycaemia with 
the first dose of sotagliflozin a 20% reduction in the first mealtime bolus insulin may be considered.  
Subsequent bolus doses should be adjusted individually based on blood glucose results. No reduction 
in basal insulin is recommended when initiating sotagliflozin. Subsequently, basal insulin should be 
adjusted based on blood glucose results. When needed, insulin dose reduction should be done 
cautiously to avoid ketosis and DKA. 
 
Ketone monitoring during treatment: 
During the initial one to two weeks of treatment with sotagliflozin, ketones should be monitored on a 
regular basis. After starting therapy, the frequency of ketone level testing (either blood or urine) 
should be individualized, according to the patient's lifestyle and/or risk factors (see section 4.4). 
Patients should be informed about what actions to take if ketone levels are elevated. The 
recommended actions are listed in Table 1. Measurement of blood ketone levels is preferred over 
urine. 
 
Table 1: Actions to take in case of elevated ketone levels  
Clinical 
stage 

Blood Ketone (beta-
hydroxybutyrate) 

Urine Ketone  Actions  

Ketonaemia 
or Ketonuria 

0.6-1.5 mmol/L  
  

Trace or Small  
+  
  

The patient may need to take 
extra rapid-acting insulin and 
drink water. Extra carbohydrates 
should be taken if the glucose 
levels are normal or low.  
 
Ketone levels should be 
measured again after two hours. 
Check glucose levels frequently 
to avoid hyperglycaemia or 
hypoglycaemia. 
 
The patient should immediately 
seek medical advice and stop 
taking sotagliflozin if levels 
persist and symptoms present.  

Impending 
DKA 

> 1.5-3.0 mmol/L  
  

Moderate  
++  
  

The patient should immediately 
seek medical advice and stop 
taking sotagliflozin. 
  
The patient may need to take 
extra rapid acting insulin and 
drink water. Extra carbohydrates 
should be taken if the glucose 
levels are normal or low.  
 
Ketone levels should be 
measured again after two hours.  
Check glucose levels frequently 
to avoid hyperglycaemia or 



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hypoglycaemia. 

Probable 
DKA 

> 3.0 mmol/L  
  

Large to very large  
+++ / ++++  
  

The patient should go to 
emergency department without 
delay and stop taking 
sotagliflozin. 
 
The patient may need to take 
extra rapid-acting insulin and 
drink water. Extra carbohydrates 
should be taken if the glucose 
levels are normal or low. 
  

  
Missed dose 
If a dose is missed, it should be taken as soon as the patient remembers the missed dose. A double 
dose should not be taken on the same day. 
 
Special populations 
 
Elderly 
No dosage adjustment is recommended based on age.  
In patients 65 years and older, renal function and an increased risk for volume depletion should be 
taken into account (see sections 4.4 and 4.8). Due to the limited therapeutic experience in patients 
aged 75 years and older, initiation of sotagliflozin therapy is not recommended.  
 
Renal impairment 
Assessment of renal function is recommended prior to initiation of sotagliflozin and periodically 
thereafter (see section 4.4). 
 
Initiation of sotagliflozin is not recommended when eGFR is less than 60 ml/min/1.73 m2 and should 
be discontinued if eGFR is persistently less than 45 mL/min/1.73 m2 (see sections 4.4 and 4.8). 
 
Sotagliflozin should not be used in patients with severe renal impairment, end stage renal disease 
(ESRD) or in patients on dialysis as it has not been studied in these patients (see sections 4.4 and 5.2). 
 
Hepatic impairment 
No dose adjustment is recommended in patients with mild hepatic impairment.  Sotagliflozin is not 
recommended in patients with moderate and severe hepatic impairment (see sections 4.4 and 5.2). 
 
Paediatric population 
The safety and efficacy of sotagliflozin in children and adolescents has not yet been established. No 
data are available. 
 
Method of administration  
 
Oral use. 
Sotagliflozin should be taken once daily before the first meal of the day. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 



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4.4 Special warnings and precautions for use 
 
Diabetic ketoacidosis 
 
Sodium-glucose co-transporter 2 (SGLT2) inhibitors should be used with caution in patients with 
increased risk of DKA. In the clinical trials (pool of two 52-week placebo-controlled trials) of 
sotagliflozin, the incidence of diabetic ketoacidosis (DKA) was higher in the sotagliflozin treatment 
group compared with the placebo group (see section 4.8). 
 
Before initiating sotagliflozin 
Before starting treatment, patients should be evaluated with respect to DKA risk.  
Sotagliflozin should not be initiated when patients are at a higher risk of DKA, such as: 
- Patients with low insulin needs. 
- Patient not on optimal insulin dose or who have recent issues with noncompliance or recurrent 

errors with insulin dosing and who are unlikely to maintain adequate insulin dosing. 
- Patients with recent or recurrent history of DKA (e.g.1 episode in the past 3 months or more than 

1 episode in the past 6 months).  
- Patients with increased insulin requirements due to acute medical illness or surgery.  
- Patients with elevated ketones levels (BHB reading is greater than 0.6 mmol/L or urine ketones 

one plus (+)). If ketones are elevated (BHB reading is greater than 0.6 mmol/L), treatment with 
sotagliflozin should not be started until the ketone levels are normal (see section 4.2). 

- Patients unable or unwilling to monitor ketones. 
- Patients who insist on maintaining caloric restriction, carbohydrate restriction or ketogenic diet or 

who chronically under-dose insulin (e.g. in order to remain in a lipolytic state).  
- Patients with excessive alcohol consumption or who use illicit drugs. 
 
Patients using an insulin infusion pump have a higher risk of DKA and should be experienced with 
pump use, common trouble-shooting strategies when interruptions of insulin delivery via pump occur 
(issues with insertion site, clogged tubing, empty reservoir, etc.) and use of supplemental insulin 
injections with pen or syringe as needed in case of pump failure.  Patients should consider monitoring 
ketones levels three to four hours after changing pump materials. Patients using a pump should also 
check their ketone levels with any suspected insulin interruption, regardless of blood glucose levels. 
Insulin injections should be given within 2 hours of an unexplained high blood glucose value and 
sotagliflozin treatment should be interrupted. If ketones are high follow instructions given above in 
Table 1 (see section 4.2). 
 
Sotagliflozin should only be given to patients: 

- with access to ketone testing materials and immediate access to a clinician if blood or urine 
ketones are elevated. 

- who are able to monitor ketone levels and are educated in when it is most appropriate to do so.  
 
During a dedicated counselling session with the patient at the time of first prescription of sotagliflozin 
the Patient/Carer Guide and Patient Alert card, also available via the QRcode or website, should be 
presented. The Patient Alert Card is also provided in the product packaging. 
 
The patient should be informed: 

- how to recognize the risk factors which can predispose to ketosis and DKA (including, but not 
limited to, recent or recurrent history of DKA, missed or reduced insulin doses, decreased 
caloric intake or severe dehydration, vigorous exercise, intercurrent illness, surgery, alcohol 
abuse, and in patients using an insulin infusion pump, insulin infusion interruption),  

- how to recognize DKA signs or symptoms, emphasizing that DKA could occur even when 
blood glucose levels are below 14 mmol/L (250 mg/dL), 

- when to discontinue sotagliflozin therapy (see section 4.2),  
- what actions to take when ketosis/DKA is suspected.  

 



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It is recommended that patients obtain several baseline blood or urine ketone levels over one to two 
weeks period prior to initiation of sotagliflozin therapy, and patients should become familiar with the 
behaviours/circumstances associated with elevated ketone levels and how to address them.  
 
Management of DKA risk 
The risk of diabetic ketoacidosis must be considered in the event of non-specific symptoms such as 
nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual 
fatigue or sleepiness.  It is possible that adverse effects occurring with sotagliflozin may be similar to 
presenting symptoms of DKA. Patients should be assessed for ketoacidosis immediately if these 
symptoms occur, by measuring the urine or blood ketones, regardless of blood glucose level. DKA 
episodes during sotagliflozin use can be atypical, with patients not having blood sugar levels as high 
as expected. This atypical presentation of DKA (i.e. normal or slightly elevated blood glucose levels) 
can delay diagnosis and treatment. 
 
During treatment with sotagliflozin 

- The patient should remain on optimal insulin dosing.  
- When needed to prevent hypoglycaemia, insulin dose reduction should be done cautiously to 

avoid ketosis and DKA (see section 4.2). 
- Consider discontinuing sotagliflozin if adequate insulinisation cannot be achieved on 

treatment. 
 
Treatment with sotagliflozin should be stopped in patients who are hospitalized for major surgical 
procedures or acute serious medical illnesses. 
 
Ketone monitoring during treatment 
After initiating sotagliflozin ketones should be monitored on a regular basis during the initial one to 
two weeks, then the frequency of ketone level testing should be individualised, according to the 
patient's lifestyle and/or risk factors. For all patients, it is recommended that ketones should be 
measured with changes to the normal routine, including reduced carbohydrate intake, intercurrent 
illness, reductions in total daily insulin dosing, physical activity and stress. Ketones should be 
measured repetitively when any signs or symptoms consistent with DKA or euglycaemic DKA are 
present. Measurement of blood ketone levels is preferred over urine.  
 
Patients must be informed about what actions to take if ketone levels are elevated. The recommended 
actions are listed in Table 1 (see section 4.2). 
 
Management of DKA 
In patients where DKA is suspected or diagnosed, treatment with sotagliflozin should be discontinued 
immediately. 
 
With sotagliflozin DKA may be present with low, normal or high blood glucose levels. DKA should 
be treated as per standard of care. Supplemental carbohydrate may be required based on glucose levels 
in addition to hydration and additional rapid acting insulin (see Table 1 in section 4.2).  
 
Restarting sotagliflozin is not recommended, unless a cause for the ketoacidosis is identified and 
resolved (e.g., pump malfunction, acute intercurrent illness, excessive reduction of insulin). 
 
Renal impairment 
 
Renal function abnormalities (increased serum creatinine and decreased eGFR) can occur after 
initiating sotagliflozin (see section 4.8). Patients with hypovolemia may be more susceptible to these 
changes.  
 
Sotagliflozin should not be initiated in patients with an eGFR < 60 mL/min and should be 
discontinued at eGFR persistently below 45 mL/min (see section 4.2 and 4.8). 
 



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Sotagliflozin should not be used in patients with severe renal impairment, end stage renal disease 
(ESRD) or in patients on dialysis as it has not been studied in these patients (see section 4.2). 
 
Monitoring of renal function is recommended as follows: 

- Prior to initiation of sotagliflozin and monitored periodically, at least yearly, thereafter (see 
section 4.2).  

- Prior to initiation of concomitant medicinal products that may reduce renal function and 
periodically thereafter. 

- More frequent, at least 2 to 4 times per year, renal function monitoring is recommended in 
patients with an eGFR below 60 mL/min/1.73 m2. 

 
Hepatic impairment 
 
There is limited experience in clinical trials in patients with moderate and severe hepatic impairment. 
Sotagliflozin is not recommended in patients with moderate and severe hepatic impairment, as 
sotagliflozin exposure is increased in these patients (see sections 4.2 and 5.2). 
 
Hypotension/ volume depletion 
 
Based on the mode of action of sodium glucose co-transporter 2 (SGLT-2) inhibitors, by increasing 
urinary glucose excretion (UGE), sotagliflozin induces an osmotic diuresis which may reduce 
intravascular volume and decrease blood pressure (see sections 4.8 and 5.1). Sotagliflozin may cause 
intravascular volume contraction (see section 4.8). Symptomatic hypotension may occur after 
initiating sotagliflozin particularly in patients with renal impairment, the elderly, in patients with low 
systolic blood pressure, and in patients on diuretics. Before initiating sotagliflozin, volume contraction 
should be assessed and volume status should be corrected if indicated. Patients should be monitored 
for signs and symptoms of hypotension after initiating therapy. 
 
In case of conditions that may lead to fluid loss (e.g., gastrointestinal illness), careful monitoring of 
volume status (e.g., physical examination, blood pressure measurements, laboratory tests including 
haematocrit) and electrolytes is recommended for patients receiving sotagliflozin. Temporary 
interruption of treatment with sotagliflozin should be considered until the fluid loss is corrected. 
 
Genital mycotic infections  
 
Consistent with the mechanism of SGLT2 inhibition with increased UGE, sotagliflozin increases the 
risk for genital mycotic infections as reported in clinical trials (see section 4.8). 
Patients with a history of chronic or recurrent genital mycotic infections are more likely to develop 
genital mycotic infections. Patients should be monitored and treated as appropriate. 
 
Urinary tract infections 
Temporary interruption of sotagliflozin should be considered when treating pyelonephritis and 
urosepsis. 
 
Elderly patients 
 
Elderly may be at an increased risk of volume depletion (see section 4.2). 
 
Lower limb amputations 
 
An increase in cases of lower limb amputation (primarily of the toe) has been observed in ongoing 
long-term, clinical studies with another SGLT2 inhibitor. It is unknown whether this constitutes a class 
effect. Like for all diabetic patients it is important to counsel patients on routine preventative foot-
care.  
 



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Necrotising fasciitis of the perineum (Fournier’s gangrene) 
 
Post-marketing cases of necrotising fasciitis of the perineum, (also known as Fournier’s gangrene), 
have been reported in female and male patients taking other SGLT2 inhibitors. This is a rare but 
serious and potentially life-threatening event that requires urgent surgical intervention and antibiotic 
treatment. 
 
Patients should be advised to seek medical attention if they experience a combination of symptoms of 
pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Be aware 
that either uro-genital infection or perineal abscess may precede necrotizing fasciitis. If Fournier’s 
gangrene is suspected, sotagliflozin should be discontinued and prompt treatment (including 
antibiotics and surgical debridement) should be instituted. 
 
Urine laboratory assessments  
 
Due to its mechanism of action, patients taking sotagliflozin will test positive for glucose in their 
urine. 
 
Drug/Laboratory test interference  
 
Interference with 1,5-anhydroglucitol (1,5-AG) Assay 
Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are 
unreliable in assessing glycaemic control in patients taking medicinal products that inhibit SGLT2. 
Alternative methods should be used to monitor glycaemic control. 
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effects of other medicinal products on sotagliflozin   
 The coadministration of a multiple dosing regimen of rifampicin, an inducer of various UGT and 
CYP metabolizing enzymes, with a single dose of 400 mg sotagliflozin resulted in a decrease in the 
AUC0-inf (60%) and Cmax (40%) of sotagliflozin. This decrease in exposure to sotagliflozin may 
decrease efficacy. If an enzyme inducer (e.g., rifampicin, phenytoin, phenobarbital, ritonavir) must be 
co-administered with sotagliflozin, consider frequent monitoring of glucose level. 
 
Interaction studies in healthy volunteers showed that metformin, metoprolol, midazolam, rosuvastatin 
and oral contraceptives had no clinically relevant effect on the pharmacokinetics of sotagliflozin. 
 
Effects of sotagliflozin on other medicinal products   
There is an increase in AUC0-inf and Cmax of digoxin (27% and 52% respectively) when co-
administered with sotagliflozin 400mg, due to inhibition of P-gp by sotagliflozin. Patients taking 
sotagliflozin with concomitant digoxin should be monitored appropriately.  
 
An increase in total exposure and Cmax of rosuvastatin of ca 1.2- and 1.4-fold, respectively, was 
demonstrated when co-administered with sotagliflozin and is not deemed clinically relevant. However, 
the mechanism behind the limited increase in exposure is not completely elucidated as sotagliflozin 
and M19 (sotagliflozin 3-O-glucuronide) are characterized as BCRP inhibitors in vitro and M19 also 
as an inhibitor OATP1B3 and OAT3. Rosuvastatin is a known OATP, BCRP and OAT3 substrate. It 
cannot be ruled out that sotagliflozin may interact with other sensitive OAT3, OATP- and/or BCRP-
substrates (e.g.: fexofenadine, paclitaxel, bosentan, methotrexate, furosemide, benzylpenicillin) 
resulting in potentially larger increases of exposure than seen for rosuvastatin. It should be evaluated if 
additional safety monitoring is needed when using these substrates. 
 
Based on in-vitro data, induction of CYP2C9, CYP2B6 and CYP1A2 cannot be ruled out. Substrates 
of these enzymes should be monitored for decreases in efficacy. 
 



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Interaction studies conducted in healthy volunteers show that sotagliflozin had no clinically relevant 
effect on the pharmacokinetics of metformin, metoprolol, midazolam and oral contraceptives. 
 
Insulin 
Insulin may increase the risk of hypoglycaemia.  A lower dose of insulin may be required to minimise 
the risk of hypoglycaemia when used in combination with sotagliflozin (see section 4.2). 
 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no data from the use of sotagliflozin in pregnant women.  
Animal studies have shown that sotagliflozin crosses the placenta.  
Animal studies do not indicate direct or indirect harmful effects with respect to fertility and pregnancy 
(see section 5.3).  Pharmacologically-related reversible renal changes were observed in a rat postnatal 
study, corresponding to the second and third trimesters of human pregnancy (see section 5.3). 
Therefore, sotagliflozin is not recommended during the second and third trimesters of pregnancy.  
As a precautionary measure, when pregnancy is detected, treatment with sotagliflozin should be 
discontinued. 
 
Breast-feeding 
 
No data in humans are available on excretion of sotagliflozin into milk.  
Available toxicological data in animals have shown excretion of sotagliflozin into milk.  
A risk to the newborns/infants cannot be excluded.  
Sotagliflozin should not be used during breast-feeding. 
 
Fertility 
 
No studies on the effect on human fertility have been conducted for sotagliflozin. Animal studies do 
not indicate direct or indirect harmful effects with respect to fertility (see section 5.3). 
 
 
4.7 Effects on ability to drive and use machines 
 
Sotagliflozin has no or negligible influence on the ability to drive and use machines.  
However, patients should be alerted to the risk of hypoglycaemia as sotagliflozin is used in 
combination with insulin. 
 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently reported adverse reactions were genital mycotic infections, diabetic ketoacidosis 
and diarrhoea. 
 
Tabulated list of adverse reactions  
 
The following adverse reactions have been identified in the pool of two 52-week placebo-controlled 
clinical trials described above.  Adverse reactions listed below are classified according to frequency 
and system organ class (SOC). Frequency categories are defined according to the following 
convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), 
rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the 
available data). 
 



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Table 2: Tabulated list of adverse reactions  
System Organ class Frequency of occurrence 
  Very common Common Uncommon 
Infections and infestations Female genital 

mycotic 
infections*,a, † 

Male genital mycotic 
infections*,b, † 
urinary tract infections*’ † 
 

 

Metabolism and nutrition 
disorders 

  
Diabetic ketoacidosis*’ †  
 

 

Vascular disorders  Volume depletion*, c, †  
Gastrointestinal disorders  Diarrhoea, flatulence 

 
 

 

Renal and urinary disorders  Increased urinationd,  
blood creatinine increased/ 
glomerular filtration 
decreased† 

 

Investigations  Blood ketone body 
increased, serum lipids 
increasede, haematocrit 
increasedf 

 

* See section 4.4 
† See subsections below for additional information. 
a Adverse event grouping, including, but not limited to, vulvovaginal mycotic infection, vaginal 
infection, vulvitis, vulvovaginal candidiasis, genital infection, genital candidiasis, genital infection 
fungal, vulvovaginitis, urogenital infection fungal.  
b Adverse event grouping, including, but not limited to, balanoposthitis, genital infections fungal, 
balanitis candida, epididymitis. 
 c Adverse events grouping, including dehydration, hypovolaemia, postural dizziness, orthostatic 
hypotension, hypotension, syncope and presyncope when reported in context of volume depletion. 
dAdverse events grouping, including urine output increased, polydipsia, micturition urgency, nocturia, 
pollakiuria and polyuria 
eMean percent changes from baseline for sotagliflozin 200 mg and 400 mg versus placebo, 
respectively, were HDL-C 3.3% and 4.2% versus 0.5%; LDL-C 5.0% and 6.1% versus 3.3%; 
triglycerides 5.7% and 5.4% versus 2.7%. 
fThe proportion of subjects that met the criteria haematocrit >50% was higher in the sotagliflozin 200 
mg and 400 mg groups (6.7% and 8.2%) compared to the placebo group (2.7%) 
 
Description of selected adverse reactions 
 
Diabetic ketoacidosis 
In placebo-controlled clinical trials of sotagliflozin, patients were advised to monitor urine or blood 
ketones in case of suspected symptoms of DKA and seek medical advice/attention if their self-
measured blood ketone reading was > 0.6 mmol/l. In the pooled 52-week data, the incidence of DKA 
was increased in a dose-dependent manner for sotagliflozin (2.9% and 3.8% for sotagliflozin 200 mg 
and 400 mg, respectively) compared to placebo (0.2%). The exposure-adjusted incidence rate was 
3.12, 4.19 and 0.21 subjects per 100 patient-years for sotagliflozin 200 mg, sotagliflozin 400 mg and 
placebo. Fifteen of the 35 cases (43%) experienced DKA with glucose values in the glycaemic range 8 
to 14 mmol/L. In the broader pool, including all type 1 diabetes mellitus patients in phase 2 and 3 
studies, the exposure-adjusted incidence rate was 3.07, 5.29 and 0.76 subjects per 100 patient-years for 
sotagliflozin 200 mg, sotagliflozin 400 mg and placebo (see section 4.4). 
 



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Volume depletion  
Sotagliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction and 
adverse reactions related to volume depletion. Adverse reactions related to volume depletion (e.g., 
hypovolemia, blood pressure decreased, blood pressure systolic decreased, dehydration, hypotension, 
orthostatic hypotension, and syncope) were reported by 2.7%, 1.1% and 1.0% of patients treated with 
sotagliflozin 200mg, sotagliflozin 400 mg and placebo. Sotagliflozin may increase the risk of 
hypotension in patients at risk for volume contraction (see section 4.4). 
 
Genital mycotic infections 
The incidence of female genital infections (e.g. vulvovaginal mycotic infection, vaginal infection, 
vulvovaginal candidiasis and vulvitis) was increased in the sotagliflozin 200 mg and 400 mg group 
(15% and 17%, respectively) as compared to placebo (4.7%). Most of the events were mild or 
moderate and no serious case was reported. Discontinuation due to genital mycotic infections occurred 
in 1.2%, 1.1% and 0.8% of patients treated with sotagliflozin 200 mg, sotagliflozin 400 mg and 
placebo, respectively.  
 
The incidence of male genital infections (e.g. balanoposthitis, genital infection fungal) was increased 
for sotagliflozin 200 mg (3.0%), sotagliflozin 400 mg (6.3%) compared to placebo (1.1%). All events 
were mild or moderate in intensity and no serious cases. Discontinuation due to genital mycotic 
infections occurred in 0%, 0.4% and 0.4% of patients treated with sotagliflozin 200 mg, sotagliflozin 
400 mg and placebo, respectively.  
 
Urinary tract infections 
The overall frequency of urinary tract infections reported were 7.1% and 5.5% for sotagliflozin 200 
mg and sotagliflozin 400 mg compared to 6.1% for placebo. The incidence of UTI in female subjects 
was 12%, 7.0% and 11% and the incidence of UTI in male subjects was 2.3%, 4.0% and 1.8% for 
sotagliflozin 200 mg, sotagliflozin 400 mg and placebo, respectively. All UTI events were mild or 
moderate in intensity except for one severe case (male subject in the sotagliflozin 400 mg group). Two 
cases (2 cases of cystitis) were serious; both occurred in male subjects in the sotagliflozin 400 mg 
group. 
 
Blood creatinine increased/Glomerular filtration decreased and renal-related events 
Sotagliflozin was associated with decreases in mean eGFR at week 4 (-4.0% and -4.3% for 
sotagliflozin 200 mg and 400 mg) versus placebo (-1.3%) that were generally reversible during 
continuous treatment. Mean increases in serum creatinine from baseline to week 4 was 4.0%, 4.3% 
and 1.4% for sotagliflozin 200mg, sotagliflozin 400 mg and placebo, respectively. At week 24 and 52 
the change from baseline in creatinine was equal to or less than 0.02 mg/dL for both sotagliflozin 200 
and sotagliflozin 400 mg. 
 
The incidence of renal-related events was low and similar across the groups (1.5%, 1.5% and 1.3% for 
sotagliflozin 200 mg, sotagliflozin 400 mg and placebo). 
 



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Table 3: Changes from baseline in serum creatinine and eGFR in the pool of two 52-week placebo-
controlled studies 
 Placebo 

(N=526) 
Sotagliflozin  
200mg 
(N=524) 

 Sotagliflozin  
400 mg 
(N=525) 

Mean baseline 
values 

N 526 524 525 
Creatinine (mg/dL) 0.85 0.85 0.85 
eGFR (mL/min/1.73 m2) 90.2 89.3 89.1 

Mean change from 
baseline at week 4 

N 511 502 505 
Creatinine (mg/dL) 0.01 0.03 0.04 
eGFR (mL/min/1.73 m2) -1.15 -3.57 -3.81 

Mean change from 
baseline at week 24 

N 481 479 477 
Creatinine (mg/dL) 0.01 0.02 0.02 
eGFR (mL/min/1.73 m2) -1.06 -1.79 -1.66 

Mean change from 
baseline at week 52 

N 374 392 380 
Creatinine (mg/dL) 0.01 0.02 0.01 
eGFR (mL/min/1.73 m2) -0.70 -2.14 -0.57 

 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
 
4.9 Overdose 
 
Multiple doses of 800 mg once daily were administrated in healthy volunteers and these doses were 
well tolerated. 
In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the 
patient's clinical status.  
The removal of sotagliflozin by haemodialysis has not been studied. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, sodium-glucose co-transporter 2 (SGLT2) 
inhibitors, ATC code: A10BK06 
 
Mechanism of action 
 
Sotagliflozin is a dual inhibitor of sodium glucose cotransporter type 1 (SGLT1) and SGLT2. Local 
intestinal inhibition of SGLT1, the major transporter for glucose absorption, delays and reduces 
glucose absorption in the proximal intestine, resulting in a blunting and delay of postprandial 
hyperglycaemia. SGLT2 is the predominant transporter responsible for reabsorption of glucose from 
the glomerular filtrate back into the circulation. By inhibiting SGLT2, sotagliflozin reduces renal 
reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases 
urinary glucose excretion. 
 

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Pharmacodynamic effects 
 
Urinary glucose excretion  
In a 12-week dose ranging study, consistent with SGLT2 inhibition, 24-h placebo corrected change 
from baseline Urinary Glucose Excretion (UGE) increased by 57.7 grams (p<0.001) and 70.5 grams 
(p<0.001) in patients with type 1 diabetes taking 200 mg and 400 mg sotagliflozin respectively, which 
is consistent with SGLT2 inhibition.  
 
Post prandial glucose reduction  
In a 12 week dose ranging study, consistent with SGLT1 inhibition, placebo corrected change from 
baseline 2-hour post prandial glucose (PPG), measured after a standardised mixed meal, was reduced 
by 1.52 mmol/L (p=0.15) and 2.73 mmol/L (p=0.006) in patients taking 200 mg and 400 mg 
sotagliflozin respectively, which is consistent with SGLT1 inhibition.   
 
Clinical efficacy and safety  
 
The efficacy and safety of sotagliflozin in patients with type 1 diabetes not adequately controlled on 
their current insulin therapy was evaluated in three double-blind, placebo-controlled studies. In 
InTandem1 (study 1) and in InTandem2 (study 2) sotagliflozin was used as add on to optimised insulin 
and in InTandem3 (Study 3) sotagliflozin was used as add on to any existing insulin regimen in 
patients not on HbA1c goal. 
 
Study 1 and study 2 
On a background of optimised insulin, the efficacy and safety of sotagliflozin 200 mg or 400 mg once 
daily versus insulin alone were evaluated in two double-blind, placebo controlled studies (study 1 
and 2) performed in 1575 patients with type 1 diabetes on insulin pump or multiple daily injection 
therapy. Each study was of 52 weeks duration, with primary and key secondary endpoints at 24 weeks.  
Beginning 6 weeks prior to randomization, insulin dose was adjusted (optimised) to achieve the 
following glycaemic goals fasting/preprandial, self-monitored blood glucose (SMBG) 4.4-7.2 mmol/L 
and 2-hour/peak postprandial SMBG glucose <10 mmol/L.  
Patients were then maintained on optimised insulin and randomized to sotagliflozin 200 mg, 
sotagliflozin 400 mg or insulin alone. For the first meal on Day 1, patients were instructed to decrease 
their calculated (or usual) mealtime carbohydrate bolus insulin by 30%. Insulin optimisation was 
continued throughout the study.  
 
In study 1, a total of 793 patients entered the study. The mean age of patients was 46 years, 8.1% were 
65 years or older. Mean duration of diabetes was 24.4 years, 60% of patients were using insulin pump 
and 40% were using multiple daily injections.  In the study 48% were male and 92% were White and 
84% of randomised patients completed the study. The mean eGFR was 87 mL/min/1.73 m2 and 5.7% 
of patients had eGFR between 45 and 60 mL/min/1.73 m2. The mean BMI was 30 kg/m2 and 23% of 
patients had SBP ≥ 130 mmHg. At screening the HbA1c was 8.21%, 8.26% and 8.20% for insulin, 
insulin+sotagliflozin 200 mg and insulin+sotagliflozin 400 mg. 
 
In study 2, a total of 782 patients entered the study. The mean age of patients was 41 years, 4.2% were 
65 years or older. Mean duration of diabetes was 18 years, 26% of patients were using insulin pump 
and 74% were using multiple daily injections. In the study 52% were male and 96.2% were White and 
87% of randomised patients completed the study. The mean eGFR was 92 mL/min/1.73 m2 and 3.3% 
had eGFR between 45 and 60 mL/min/1.73 m2. The mean BMI was 28 kg/m2 and 32% of patients had 
SBP ≥ 130 mmHg. At screening the HbA1c was 8.42%, 8.35% and 8.38% for insulin, 
insulin+sotagliflozin 200 mg and insulin+sotagliflozin 400 mg.     
 
At week 24, treatment with 200 mg or 400 mg sotagliflozin provided statistically significant 
reductions in HbA1c (p-value <0.001) compared to insulin alone. Treatment with sotagliflozin also 
resulted in reduction in body weight and FPG compared with insulin alone (see Table 4).  
 



14 

Main results for insulin dose and Diabetes Treatment Satisfaction Questionnaire and Diabetes Distress 
Screening Scale are presented in Table 4. 



15 

Table 4: Results at 24-week trial with sotagliflozin in patients with type 1 diabetes mellitus inadequately 
controlled on insulin (Study 1 – Study 2) 
 

 Study 1 Study 2 
 
 

Insulin  Insulin + 
sotagliflozi
n 200 mg 

Insulin + 
sotagliflozin 

400 mg 

Insulin  Insulin + 
sotagliflozin 

200 mg 

Insulin + 
sotagliflozin 

400 mg 
N 268 263 262 258 261 263 
HbA1c (%) 
 Baseline 
(after 6-week 
insulin 
optimisation), 
mean  

7.54 7.61 7.56 7.79 7.74 7.71 

At Week 24, 
mean 

7.50 7.17 7.08 7.79 7.36 7.35 

Change from 
baseline, LS 
mean 

-0.07 -0.43 -0.48 -0.02 -0.39 -0.37 

Difference 
from insulin 
alone, LS 
mean 
[95%CI] 

N/A -0.36 * 
 

[-0.45,  
-0.27] 

-0.41 * 
 

[-0.50,  
-0.32] 

N/A -0.37* 
 

[-0.48,  
-0.25] 

-0.35* 
 

[-0.47, -0.24] 

HbA1c < 
7.0% at week 
24, n (%) 

61 (22.8) 97 (36.9) 123(46.9) 39 (15.1) 87 (33.3) 89 (33.8) 

Body Weight (kg) 
 Baseline, 
mean 

87.30 86.96 86.50 81.08 81.93 81.97 

Change from 
baseline, LS 
mean 

0.78 -1.57 -2.67 0.11 -1.88 -2.47 

Difference 
from insulin 
alone, LS 
mean 
[95%CI] 

N/A -2.35 * 
 

[-2.85,  
-1.85] 

-3.45 * 
 

[-3.95,  
-2.94] 

N/A -1.98 * 
 

[-2.53,  
-1.44] 

-2.58 * 
 

[-3.12, -2.04] 

Bolus insulin dose (units/day) 
 Baseline, 
mean 

31.72 30.27 30.75 32.08 31.12 31.89 

% Change 
from baseline, 
LS mean 

3.89 -1.80 -8.78 5.90 -7.04 -10.47 

% Difference 
from insulin 
alone, 
adjusted  
mean  
[95%CI] 

N/A -5.70†  
 

[-12.82, 
1.42] 

-12.67 * 
 

[-19.79,  
-5.55] 

N/A -12.95* 
 

[-20.50,  
-5.38] 

-16.37* 
 

[-23.90, -8.83] 

Diabetes Treatment Satisfaction Questionnaire 
Baseline, 
mean 

28.9 28.4 29.2 28.2 28.3 28.4 

Difference 
from placebo, 
LS mean 
[95%CI] 

N/A 2.5 
 

[1.7, 3.3] 

2.5 
 

[1.8, 3.3] 

N/A 2.0 
 

[1.3, 2.7] 

1.7 
 

[1.0, 2.4] 

Diabetes Distress Screening Scale 
Baseline 
score, mean 

5.0 5.1 4.9 5.3 5.6 5.5 

Difference N/A -0.7* -0.8* N/A -0.3 -0.4 

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 Study 1 Study 2 
 
 

Insulin  Insulin + 
sotagliflozi
n 200 mg 

Insulin + 
sotagliflozin 

400 mg 

Insulin  Insulin + 
sotagliflozin 

200 mg 

Insulin + 
sotagliflozin 

400 mg 
from placebo, 
LS mean  
[95%CI] 

 
[-0.9, -0.4] 

 
[-1.0, -0.5] 

 
[-0.6, -0.0] 

 
[-0.7, -0.2] 

Basal insulin dose (units/day) 
Baseline, 
mean 

35.06 34.84 33.39 29.76 29.18 29.50 

% Change 
from baseline, 
LS mean 

3.77 -1.73 -5.35 1.66 -4.16 -3.01 

% Difference 
from insulin 
alone, LS 
mean  
[95% CI] 

N/A -5.51* 
 

[-8.71,  
-2.30] 

-9.12* 
 

[-12.32,  
-5.91] 

N/A -5.82 
 

[-10.04,  
-1.59] 

-4.67 
 

[-8.88, -0.47] 

N: all randomised and treated patients 
Post-Baseline LS means, LS mean differences, 95% CLs, and p-values for each individual study were obtained from 
accounting for missing data 
*p <0.001 
† p 0.12 
‡ p=0.034 
 
No differences in HbA1c decrease could be detected across subgroups including age, gender, race, 
geographic region, baseline BMI, age at diagnosis, baseline HbA1c, eGFR, duration of disease and 
insulin delivery method. 
 
In studies 1 and 2 combined, patient 24-week completion rates were 89.5% among insulin alone 
patients, and 91.4% and 90.7% among patients receiving 200 mg and 400 mg of sotagliflozin, 
respectively.  The 52-week completion rates were 84.2%, 86.6%, and 85.3% respectively.   
 
Efficacy over a 52-week period 
At the end of 24 weeks the reduction in HbA1c was -0.36% and -0.38% and at 52 weeks it was -0.23% 
and -0.32% with sotagliflozin 200mg and 400 mg, respectively. The proportion of patients with A1C 
<7.0% at 24 weeks was 19.0% for placebo, 35.1% for sotagliflozin 200mg, 40.4% for sotagliflozin 
400mg and at 52 weeks was 18.3%, 28.6% and 31.6% for placebo, sotagliflozin 200 mg and 400 mg 
respectively.  
At the end of 52 weeks the reduction in body weight, mean daily bolus insulin dose, FPG were 
sustained compared to insulin alone. 
 
CGM substudy: 2-hr PPG and time in range 
From study 1 and study 2, 278 subjects participated in a blinded continuous glucose monitoring 
(CGM) sub-study (see Table 5). 
 

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Table 5: Results of CGM sub study at week 24 (Pooled data, study 1 and study 2) 
 

Characteristic 
Insulin Insulin + 

sotagliflozin 
200 mg 

Insulin + 
sotagliflozin 
400 mg 

N 93 89 96 
Percent Time in range 3.9-10.0 mmol/L    
 Baseline (after 6-week insulin optimisation) , LS mean 52.30 52.19 50.66 
Change from baseline, LS mean -1.26 4.09 10.45 
Difference from insulin alone, LS mean % (p-value) N/A 5.35 (0.026)* 11.71 (<0.001) 

† 
2-hour postprandial glucose following a standardized 
mixed meal, mmol/L 

   

 Baseline (after 6-week insulin optimisation), mean 12.76 11.75 11.64 
 Change from baseline, LS mean -0.44 -2.37 -2.71 
 Difference from insulin alone, LS mean (p-value) N/A -1.93 (0.004) -2.27 (<0.001) 

* 5.35% more time in range, correspond to 1.3 hours 
† 11.71% more time in range, correspond to 2.8 hours 

 
Study 3 
InTandem 3 (study 3) was a 24-week duration study performed on a background of existing insulin 
regimen in type 1 diabetes patients with screening HbA1c ≥7.0% to ≤11.0%, to evaluate efficacy and 
safety of sotagliflozin 400 mg once daily versus insulin alone.  
For the first meal on Day 1, patients were instructed to decrease their calculated (or usual) mealtime 
carbohydrate bolus insulin by 30%. 
The mean age of patients was 43 years, 7.2% were 65 years or older. Mean duration of diabetes was 
20 years, 39% of patients were using insulin pump and 61 % were using non-pump insulin therapy. 
In the study 50% were male and 88 % were White and 87% of randomised patients completed the 
study. The mean eGFR was 92 mL/min/1.73 m2 and 5 % had eGFR between 45 and 60 mL/min/1.73 
m2. The mean BMI was 28 kg/m2 and 29% had SBP ≥ 130 mmHg. 
 
At week 24, treatment with 400 mg sotagliflozin before the first meal of the day resulted in 
statistically significant more patients achieving the net benefit primary endpoint (proportion of patients 
with HbA1c <7.0% at week 24 and no episode of severe hypoglycaemia, and no episode of DKA from 
randomisation to Week 24) compared with insulin alone (28.6% versus 15.2%) (p-value<0.001) 
and  provided statistically significant mean reductions in HbA1c (p-value <0.001). 
Treatment with sotagliflozin also resulted in reduction in body weight and bolus insulin dose 
compared with insulin alone (see Table 6). Treatment with sotagliflozin also resulted in reduction in 
body weight and systolic blood pressure (in patients with baselines SBP ≥130 mmHg) compared with 
insulin alone (see Table 6).  Main results regarding insulin dose are presented in Table 6. 
 

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Table 6: Efficacy results of a 24 week placebo-controlled study of sotagliflozin as add-on to insulin therapy 
in patients not at HbA1c goal (Study 3): 

 
Characteristic 

Insulin Insulin + 
sotagliflozin 400 
mg 

N 703 699 
HbA1c (%)  
Baseline, LS mean 8.21 8.26 
Change from baseline,  mean -0.33 -0.79 
Difference from insulin alone, LS mean 
[95% CI] 

N/A - 0.46† 
[-0.54, -0.38] 

HbA1c < 7.0% at week 24, n (%) 111 (15.8) 207 (29.6) 
Body Weight (kg) 
 Baseline, mean  81.55 82.40  
 Change from baseline, LS mean 0.77 -2.21 
 Difference from insulin alone, LS mean 
[95% CI] 

N/A - 2.98† 
[-3.31, -2.66] 

Bolus insulin 
 Baseline, mean in units  28.72 27.34  
% change from baseline, LS mean 6.62 -5.71 
% difference from insulin alone, LS 
mean 

N/A -12.32† 

Basal insulin  
 Baseline, mean in units/day 29.63 29.54 
 % change from baseline, LS mean 6.76 -3.11 
% difference from insulin alone, LS  
mean 

N/A -9.88† 

Systolic Blood Pressure in those with baseline SBP ≥ 130 mmHg* 
N 203 203 
Baseline, mean in mmHg 139.9   140.5 
Change from baseline, LS mean -5.7 -9.2 
Difference from insulin alone, adjusted  
mean [95% CI] 

N/A -3,5‡ 
[-5.7, -1.3] 

*Systolic blood pressure was assessed at week 16 
† p <0.001 
‡ p=0.002 
 
Hypoglycaemia 
The incidence of severe hypoglycaemia and rates of documented hypoglycaemia (overall and 
nocturnal) were lower on sotagliflozin compared to insulin alone in the 52-week studies, as shown in 
Table 7. 
 

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Table 7: Incidence of severe hypoglycaemia and rates of documented, (overall and nocturnal) 
hypoglycaemic events in the pool of two 52-week placebo-controlled clinical studies  

Insulin  
(N=526) 

Insulin + 
sotagliflozin  

200 mg 
(N=524) 

Insulin + 
sotagliflozin  

400 mg 
(N=525) 

Incidence of severe 
hypoglycaemia (%)* 

7.4 5.7 4.4 

Reduction in risk of severe 
hypoglycaemia compared to 
insulin alone (%) 

- 24a 41 b 

Rate of documented 
hypoglycaemia† (events per 
patient year) at thresholds of 
≤3.1 or ≤3.9 mmol/L 

≤3.1 mmol/L: 19.0 
≤3.9 mmol/L: 95.6 

≤3.1 mmol/L: 14.9  
≤3.9 mmol/L: 81.3 

≤3.1 mmol/L: 15.0 
≤3.9 mmol/L: 83.7 

Reduction in risk of 
documented hypoglycaemia, 
compared to insulin alone at 
threshold of ≤3.1 mmol/L (%) 

- 21 c 18 c 

Rate of nocturnal‡  documented 
hypoglycaemia† (events per 
patient year) at thresholds of 
≤3.1 or ≤3.9 mmol/L 

≤3.1 mmol/L: 2.7 
≤3.9 mmol/L: 12.2 

≤3.1 mmol/L: 2.3  
≤3.9 mmol/L: 11.0 

≤3.1 mmol/L: 2.3  
≤3.9 mmol/L: 11.1 

    
* Defined as an event consistent with hypoglycaemia where the patient required the assistance of another 
person to recover, lost consciousness, or experienced a seizure (regardless of whether biochemical 
documentation of a low glucose value was obtained). All severe hypoglycaemia presented were positively 
adjudicated.  
† Defined as a documented SMBG or laboratory blood glucose value below or equal to threshold of 3.1 or 
3.9 mmol/L.  
‡ Defined as event that occurred between 00:00 and 05:59 hours. 
a p=0.28 
b p=0.04 
c p<0.01 

 
In study 3 at 24 weeks incidences of severe hypoglycaemia were 2.4% and 3.0% on placebo and 
sotagliflozin 400 mg, respectively and the reduction in the rate of hypoglycaemic events at 24 weeks 
(blood glucose ≤3.1 mmol/L) for sotagliflozin 400 mg was 22% (p<0.001) compared to insulin alone. 
 
Patients with renal impairment  
In the 3 Phase 3 randomized clinical studies in patients with type 1 diabetes, patients with 
eGFR < 45 mL/min/1.73 m2 were excluded, 79 patients exposed to sotagliflozin had an 
eGFR < 60 mL/min/1.73 m2 and 841 patients had an eGFR ≥ 60 to ≤ 90 mL/min/1.73 m2. The HbA1c 
reduction observed in patients with eGFR ≥60 to <90 mL/min/1.73 m2 was comparable to the HbA1c 
reduction observed in patients with eGFR ≥90 mL/min/1.73 m2. In patients with eGFR <60 
mL/min/1.73 m² a numerical HbA1c reduction was observed. No overall differences in safety were 
observed with sotagliflozin treatment as compared to insulin alone in subjects with eGFR between 45 
and 60 mL/min/1.73 m2.  
 
Fasting plasma glucose 
In a pre-specified pooled analysis of study 1 and study 2, treatment with sotagliflozin as adjunct to 
insulin resulted in LS mean changes from baseline in FPG of -0.56 mmol/l for sotagliflozin 200 mg 
and -0.87 mmol/l for sotagliflozin 400 mg compared to insulin alone (0.32 mmol/l) at week 24. 
In study 3 there was a significant reduction in FPG of 0.79 mmol/L (p<0.001) with sotagliflozin 400 
mg at 24 weeks compared to insulin alone. 
 

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Blood pressure 
In a pre-specified pooled analysis of study 1 and study 2, treatment with sotagliflozin as adjunct to 
insulin resulted in a reduction of SBP (-0.6 mmHg for placebo, -2.6 mmHg for sotagliflozin 200 mg 
and -4.1 mmHg for sotagliflozin 400 mg) at week 12. Pooled analysis of change in SBP in patients 
with baseline SBP ≥130 mmHg showed greater reduction in SBP at week 12 (-5.4 mmHg for placebo, 
-9.0 mmHg for sotagliflozin 200 mg and -10.7 mmHg for sotagliflozin 400 mg). 
 
Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Zynquista in one or more subsets of the paediatric population in type 1 diabetes mellitus (see section 
4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics (PK) of sotagliflozin has been characterized in healthy subjects and in diabetic 
patients. No clinically relevant differences were noted between the two populations.   
 
Absorption 
 
The median Tmax ranged from 1.25 to 3 hours, over a single-dose range of 400 to 2000 mg. Following 
administration of multiple doses (400 and 800 mg dose), the median Tmax values ranged from 2.5 to 4 
hours.  
The fraction of drug absorbed following administration of a single dose of [14C]-sotagliflozin was 
estimated to be at least 71%, based on the detected percentage of dose of radioactivity in the urine and 
for the metabolites of sotagliflozin in the faeces.  
When sotagliflozin tablets were administered with a high-caloric breakfast, plasma exposure to 
sotagliflozin as measured by Cmax and AUC0 inf was about 2.5- and 1.5-fold higher, respectively, 
compared to fasted condition.  
 
Distribution 
 
Both sotagliflozin and its major human metabolite 3-O-glucuronide (M19), exhibited high binding to 
human plasma proteins in vitro (fraction unbound approx. 2%) which was not dependent on the 
concentration of sotagliflozin and M19. In clinical studies the high protein binding was confirmed and 
was not influenced by reduced renal or hepatic function.  
The apparent volume of distribution of sotagliflozin following administration of a single 400 mg oral 
dose of [14C]-sotagliflozin was found to be very high with a mean value of 9392 L.  
 
Biotransformation 
 
In healthy subjects following the administration of a single dose of 400 mg [14C]-sotagliflozin 
indicated that sotagliflozin was extensively metabolized predominantly to M19 which represented 
94% of the radioactivity in plasma.  
The primary route of metabolism of sotagliflozin in humans is glucuronidation by the uridine 5’-
diphospho-glucuronosyltransferases primarly by UGT1A9, and to a much lesser extent by UGT1A1 
and UGT2B7 as well as oxidation, by CYP3A4. 
When sotagliflozin is incubated with UGT1A9, M19 was the main conjugate observed. No acyl 
glucuronides of sotagliflozin were identified. 
 
In in vitro studies, sotagliflozin did not inhibit CYP 1A2, 2C9, 2C19, 2D6, or 3A4, nor induced CYP 
1A2, 2B6, or 3A4.   
Sotagliflozin and M19 have no significant potential to inhibit OCT1, OCT2, OAT1, OAT3, OATP1B1 
and OATP1B3.   
M19 is an inducer and inhibitor of CYP3A4 and an inhibitor of CYP2D6. 
In vitro sotagliflozin was shown to have inhibitory effects on P-gp and breast cancer resistance protein 
(BCRP). M19 demonstrated inhibitory effects against OATP1B1/B3 and MRP2 in-vitro. 
 



21 

Elimination/excretion 
 
Following the administration of a single dose of 400 mg [14C]-sotagliflozin, showed 57% and 37% of 
the radioactivity were excreted in the urine and faeces, respectively. These results indicate that the 
main route of elimination of drug related material was renal.   
The predominant metabolite detected in urine was M19, representing a mean of 33% of the 
administered radioactive dose. Unchanged [14C]-sotagliflozin was the predominant radioactive peak 
detected in faecal extracts representing a mean of 23% of the total administered radioactive dose. In 
healthy volunteers, mean apparent total body clearance (CL/F) of sotagliflozin ranged from 261 to 
374 L/hr. The CL/F estimated using a population PK, which mostly evaluated T1DM patients, was 
239 L/hr. Mean terminal T1/2 ranged from 21 to 35 hours for sotagliflozin and from 19 to 26 hours for 
M19. 
 
Linearity/non-linearity 
 
The PK of sotagliflozin appeared to be dose proportional in the therapeutic dose range of 200 mg to 
400 mg QD.  
 
Special populations 
 
Renal impairment 
Exposure of sotagliflozin was evaluated in a dedicated study of subjects with mild (creatinine 
clearance [CLcr]: 60 to less than 90 mL/min) and moderate (CLcr: 30 to less than 60 mL/min) renal 
impairment and with normal renal function. In subjects with renal impairment, exposure to 
sotagliflozin following a single dose of 400 mg was approximately 1.7 fold higher in subjects with 
mild and up to 2.7 fold higher in subjects with moderate renal impairment compared to subjects with 
normal renal function.   
The apparent clearance of sotagliflozin decreases with decreasing renal function. A population PK 
model integrating data from renally impaired patients and healthy subjects estimated for subjects with 
CKD Stage II (eGFR ≥60 and <90 mL/min/1.73 m2) and CKD Stage IIIa (eGFR ≥45 and <60 
mL/min/1.73 m2) that sotagliflozin exposures were 1.5 fold higher compared to subjects with normal 
renal function. For subjects with CKD Stage IIIb (eGFR ≥30 and <45 mL/min/1.73 m2) and CKD 
Stage IV (eGFR ≥15 and <30 mL/min/1.73 m2) sotagliflozin exposures were 1.95 and 2.25 fold higher 
compared to subjects with normal renal function. 
 
Hepatic impairment  
In a study with subjects with reduced hepatic function, AUC of sotagliflozin was not increased in mild 
(Child Pugh A) hepatic impaired subjects, but was increased by ~3 fold in moderate (Child Pugh B) 
and ~ 6 fold in severe (Child Pugh C) hepatic impaired subjects.  
No dose adjustment is needed in patients with mild hepatic impairment.  
 
Elderly 
Based on a population PK analysis, age had no clinically meaningful effect on the pharmacokinetics of 
sotagliflozin. 
 
Body weight  
Based on a population PK analysis, sotagliflozin exposure was found to decrease with increased body 
weight. Consequently, low-weight patients may have somewhat increased exposure and patients with 
high weight somewhat decreased exposure. However, the differences in exposure were not considered 
clinically meaningful and therefore no dose adjustment is required based on weight. 
 
Gender and race  
Based on a population PK analysis gender and race had no clinically meaningful effect on the PK of 
sotagliflozin. 
 



22 

Paediatric patients 
No data are available. 
 
 
5.3 Preclinical safety data 
 
In a rat carcinogenicity study, a statistically significant increase in thyroid follicular cell carcinoma 
was observed in males at 75 mg/kg/day, approx. 14 times the MRHD, the highest dose evaluated.  In a 
repeat-dose study evaluating potential mechanisms responsible for the increase incidence of thyroid 
carcinoma observed in the rat carcinogenicity study, it was concluded that the increase was associated 
with a sotagliflozin-related increase in thyroid stimulating hormone (TSH). In the rat, TSH was 
considered the primary carcinogen with sotagliflozin functioning as a secondary carcinogen. These 
changes were not considered relevant for humans as TSH is not carcinogenic in humans. 
 
Sotagliflozin was not mutagenic or clastogenic. 
 
In a fertility study in rats, sotagliflozin had no effect on reproductive performance, fertility, and 
embryo/fetal viability. 
 
In a juvenile toxicology study in rats, renal changes were observed when sotagliflozin was 
administered during a period of renal development corresponding to the late second and third 
trimesters of human pregnancy.  Exposure was approximately 5 times (males) and 11 times (females) 
the clinical exposure at the Maximum Recommended Human Dose (MRHD) and caused reversible 
renal tubular dilation.   
In embryo-fetal development studies in rats and rabbits, sotagliflozin was orally administered at doses 
up to 350 mg/kg in rats and 200 mg/kg in rabbits.  In the rat study, embryo-lethality, effects on fetal 
growth along with cardiovascular and skeletal abnormalities were observed at an exposure multiple of 
158-times the human exposure at 400 mg/day. The adverse effects on embryo-fetal development at 
350 mg/kg/day were associated with maternal toxicity (body weight loss/decreased body weight gain 
and decreased food consumption during gestation day (GD) 6 to 8). Exposure at the rat no-observed-
effect level was 40-times the exposure at the MRHD.  No developmental toxicity was observed at 
doses up to 200 mg/kg/day in the rabbit, which was up to 9-times the human exposure at the MRHD. 
 
In a pre-/post-natal development study, no sotagliflozin-related adverse effects in pregnant and 
lactating females and offspring development were observed in rats  
In a study evaluating the potential effects of sotagliflozin on the development of juvenile rats, no 
sotagliflozin-related toxicity was observed following the administration of oral doses up to 
approximately 18 and 31 fold that of the MRHD (400 mg/day) for males and females, respectively. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Microcrystalline cellulose (E460i) 
Croscarmellose sodium  
Colloidal anhydrous silica 
Magnesium stearate 
Talc 
 
Film-coating 
 
Poly(vinyl alcohol) 
Macrogol 
Titanium dioxide (E171) 



23 

Talc 
Indigo carmine aluminium lake (E132). 
 
Printing ink 
 
Shellac 
Iron oxide black (E172) 
Propylene glycol 
 
6.2 Incompatibilities 
 
Not applicable.  
 
6.3 Shelf life 
 
30 months 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
PVC/PCTFE/Aluminium opaque blisters. 
Pack sizes of 10, 20, 30, 60, 90, 100, 180 film-coated tablets, and a multipack of 200 film-coated 
tablets (2 packs of 100 film-coated tablets). 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Navigant Germany GmbH 
Albrechtstr. 10c  
10117 Berlin 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Zynquista 200 mg film coated tablets: 
EU/1/19/1363/001 10 film coated tablets 
EU/1/19/1363/002 20 film coated tablets 
EU/1/19/1363/003 30 film coated tablets 
EU/1/19/1363/004 60 film coated tablets 
EU/1/19/1363/005 90 film coated tablets 
EU/1/19/1363/006 100 film coated tablets 
EU/1/19/1363/007 180 film coated tablets 
EU/1/19/1363/008 200 (2x100) film coated tablets (multipack) 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 April 2019 



24 

 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
 



26 

A.  MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer(s) responsible for batch release 
 
Sanofi Winthrop Industrie 
1 rue de la Vierge 
Ambares et Lagrave 
33565 Carbon Blanc Cedex 
France 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

• Periodic safety update reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent 
updates of the RMP. 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 
• Additional risk minimisation measures 
 
Prior to launch of Zynquista (sotagliflozin), as an adjunct to insulin therapy to improve glycaemic 
control in adults with type 1 diabetes mellitus with a Body Mass Index (BMI) ≥ 27 kg/m2, who have 
failed to achieve adequate glycaemic control despite optimal insulin therapy, in each Member State, 
the Marketing Authorisation Holder (MAH) must agree the content and format of educational 
materials for sotagliflozin, including communication media, distribution modalities, and any other 
aspects of the programme, with the National Competent Authority.  
The educational materials are aimed at providing guidance on how to manage risk of diabetic 
ketoacidosis (DKA) in patients with type 1 diabetes. 



27 

The MAH shall ensure that in each Member State where sotagliflozin is marketed, all healthcare 
professionals and patients/carers who are expected to prescribe, dispense or use the product have 
access to: 
• Guide for Health Care Professionals including a prescriber’s checklist 
• Patient’s/Carer’s Guide 
• Patient Alert Card 
 
The guide for healthcare professionals including the prescriber’s checklist should contain the 
following key elements: 
 
• Sotagliflozin is not a substitute for insulin (and does not alter insulin-sensitivity). 
• The risk of DKA is increased with sotagliflozin treatment. 
• If treated with sotagliflozin, glucose levels will not adequately reflect insulin needs, and DKA 

may occur in patients treated with sotagliflozin even if blood glucose levels are below 14 mmol/l 
(250 mg/dl). Therefore, glucose monitoring must be supplemented by ketone monitoring. 

• Patients with euglycaemic DKA may need glucose in addition to standard of care for DKA and 
sotagliflozin should be discontinued if DKA occurs. 

• Guidance to the physician for assessing whether the patient is eligible for sotagliflozin 
prescription, e.g. patient selection criteria including adherence to insulin treatment and insulin 
thresholds, patient’s beta-hydroxybutyrate (BHB) < 0.6 mmol/L or urine ketones < 1+, BMI ≥ 
27 kg/m2, absence of DKA risk factors.   

• Guidance to the physician for assessing whether the patient is prepared and engaged to perform 
self-ketone testing before and during therapy. 

• Summary of the recommendations for patients, particularly regarding blood ketone measurement 
and managing sick days. 

• For pump users: restrict sotagliflozin prescription to patients experienced in pump use, common 
trouble-shooting strategies when interruptions of insulin delivery via pump occur in case of pump 
failure. 

• Counsel the patient and evaluate their adherence to ketone monitoring while establishing their 
baseline ketone level 1 to 2 weeks before treatment initiation and ensure the patient 
o Has received education/training in ketone testing and interpreting/acting upon test results. 
o Is willing/able to perform ketone testing as prescribed. 
o Is adequately informed about managing sick days.  

• Ensure the patient is on optimal insulin therapy prior to initiation of sotagliflozin treatment. 
• Sotagliflozin treatment should be temporarily stopped before surgical procedures or in case of 

hospitalisation for acute serious illness. 
• If addition of sotagliflozin leads to marked reduction of insulin need, discontinuation of 

sotagliflozin should be considered to avoid high risk of DKA. 
 
The patient’s/carer’s guide should contain the following key elements: 
 
• Sotagliflozin is not a substitute for insulin. 
• DKA may occur in patients treated with sotagliflozin even if blood glucose levels are below 

14 mmol/l (250 mg/dl), i.e. an explanation of the concept of euglycaemic DKA. 
• Signs/symptoms of DKA - if not adequately managed DKA can be severe and fatal. 
• How to measure ketones, how to interpret the results and what to do in case of 

hyperketonaemia/DKA (contact HCP immediately if BHB > 0.6 mmol/L with symptoms or if 
BHB > 1.5 mmol/L with or without symptoms). 

• Insulin dose reduction during treatment should only be done when needed to prevent 
hypoglycaemia and should be done cautiously to avoid ketosis and DKA. 

• Do not start caloric restriction or carbohydrate restriction while treated with sotagliflozin. 
 
The patient alert card should contain the following key elements: 
 
• The patient alert card should be presented to any HCP consulted. 



28 

• DKA may occur in patients treated with sotagliflozin even if blood glucose levels are below 
14 mmol/l (250 mg/dl). 

• Signs/symptoms of DKA. 
• Patients with euglycaemic DKA should receive glucose, insulin and fluids for DKA, sotagliflozin 

should be discontinued. 
• Sotagliflozin should be temporarily stopped before surgical procedures or hospitalisation for acute 

serious illness. 
• Contact details of the sotagliflozin ‘prescriber’ and ‘Name of patient’. 
 

• Obligation to conduct post-authorisation measures  
 

The MAH shall complete, within the stated timeframe, the below measures: 

Description Due date 

Non-interventional PASS: In order to estimate the incidence of DKA in T1DM 
sotagliflozin treated patients to assess the effectiveness of the risk minimisation 
measures implemented in Europe, the MAH should conduct and submit the results 
from an observational cohort study using existing data sources in European 
countries where sotagliflozin will be launched for T1DM.  

31/12/2024 

 



29 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON with blue box 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zynquista 200 mg film-coated tablets 
sotagliflozin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 200 mg sotagliflozin. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
10 film-coated tablets 
20 film-coated tablets 
30 film-coated tablets 
60 film-coated tablets 
90 film-coated tablets 
100 film-coated tablets 
180 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



32 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Navigant Germany GmbH 
Albrechtstr. 10c  
10117 Berlin 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1363/001 (200 mg – 10 film coated tablets) 
EU/1/19/1363/002 (200 mg – 20 film coated tablets) 
EU/1/19/1363/003 (200 mg – 30 film coated tablets) 
EU/1/19/1363/004 (200 mg – 60 film coated tablets) 
EU/1/19/1363/005 (200 mg – 90 film coated tablets) 
EU/1/19/1363/006 (200 mg – 100 film coated tablets)  
EU/1/19/1363/007 (200 mg – 180 film coated tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Zynquista 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



33 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON multipack (with Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zynquista 200 mg film-coated tablets 
sotagliflozin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 200 mg sotagliflozin. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
Multipack: 200 (2 packs of 100) film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



34 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Navigant Germany GmbH 
Albrechtstr. 10c  
10117 Berlin 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/19/1363/008  200 film-coated tablets (2 packs of 100) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
16. INFORMATION IN BRAILLE 
 
Zynquista 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



35 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INNER CARTON without Blue Box 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zynquista 200 mg film-coated tablets 
sotagliflozin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 200 mg sotagliflozin. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
100 film-coated tablets 
Component of a multipack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 



36 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Navigant Germany GmbH 
Albrechtstr. 10c  
10117 Berlin 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1363/008  (200 mg – 2 packs of 100 film coated tablets)  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
16. INFORMATION IN BRAILLE 
 
Zynquista 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 



37 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zynquista 200 mg tablets 
sotagliflozin 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Navigant Germany GmbH 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



38 

Patient Alert Card 
 
Patient Alert Card 
This card contains important safety information about diabetic ketoacidosis (DKA) 
▼This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. You can help by reporting any side effects you may get: [To be adjusted per 
Country (include phone number…)] 
 
Information for the patient:  
Please carry this card with you at all times and show it to any healthcare professional (HCP) consulted 
in order to inform them about your current treatment with ZYNQUISTA. 
 
Please consult the Patient/Carer’s Guide for more information discussed with your doctor about taking 
Zynquista and the risk of DKA. Read the Zynquista package leaflet for full information and 
instructions for use. 
 
Information for healthcare professionals: 
This patient is using ZYNQUISTA for the treatment of Type 1 Diabetes Mellitus (T1DM). This 
treatment is indicated as an adjunct to insulin therapy to improve glycaemic control in adults with 
T1DM with a BMI ≥27 kg/m2, who have failed to achieve adequate glycaemic control despite optimal 
insulin therapy. 
 
• ZYNQUISTA increases the risk of DKA. DKA may occur in patients treated with Zynquista even 

if blood glucose levels are below 14 mmol/l (250 mg/dl). This atypical presentation of DKA can 
delay diagnosis and treatment.  

• For patients taking ZYNQUISTA, glucose is not a reliable marker for DKA and must be 
supplemented with ketone monitoring 

• Signs and symptoms of DKA include: 
- nausea, vomiting, or abdominal pain 
- anorexia 
- excessive thirst 
- unusual fatigue or sleepiness  
- difficulty breathing 
- confusion 

• Hold Zynquista immediately if patient’s BHB level is > 0.6 mmol/L (1+ urine ketone) with 
symptoms or if BHB > 1.5 mmol/L (2+ urine ketone) with or without symptoms. 

• Patients with euglycaemic DKA should receive glucose, insulin and fluids for DKA management, 
sotagliflozin should be discontinued. 

• ZYNQUISTA should be temporarily stopped before surgical procedures or hospitalisation for 
acute serious illness. 
 
 
Patient name:-------------------------- 
Date ZYNQUISTA first prescribed:--------------------------- 
Center name:--------------------------- 
Treating HCP name:------------------ 
Treating HCP contact number:---------------------- 

 



39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



40 

Package leaflet: Information for the patient 
 

Zynquista 200 mg film-coated tablets 
sotagliflozin 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Zynquista is and what it is used for  
2. What you need to know before you take Zynquista  
3. How to take Zynquista  
4. Possible side effects  
5. How to store Zynquista  
6. Contents of the pack and other information 
 
 
1. What Zynquista is and what it is used for 
 
Zynquista contains the active substance sotagliflozin, a medicine which lowers blood glucose (blood 
sugar) levels. Sotagliflozin works by slowing and reducing the absorption of glucose from food, and 
by increasing the amount of glucose that is passed out in urine. Together these actions help to lower 
the increased amount of glucose in the blood that occurs in patients with diabetes. 
 
Zynquista is used as an addition to insulin treatment in adults with type 1 diabetes with a body mass 
index (BMI) greater than or equal to 27. BMI is a measure of your weight in relation to your 
height.Type 1 diabetes is a disease where your body’s immune system destroys the insulin-producing 
cells in the pancreas and the body produces little to no insulin, the hormone that normally controls the 
level of your blood sugar. 
 
It is important that you also continue with your diet and exercise plan and insulin treatment as agreed 
with your doctor, pharmacist or nurse. 
 
 
2. What you need to know before you take Zynquista  
 
Do not take Zynquista: 
• if you are allergic to sotagliflozin or any of the other ingredients of this medicine (listed in 

section 6). 
 
 
Warnings and precautions  
 
Diabetic ketoacidosis (DKA) is a potentially life-threatening problem you can get with diabetes 
because of increased levels of “ketone bodies” in your urine or blood, seen in tests. If you develop 
symptoms contact your doctor or go to the nearest hospital right away. 



41 

The risk of developing diabetic ketoacidosis may be increased with prolonged fasting, excessive 
alcohol consumption, drug abuse, dehydration, sudden reductions in insulin dose, or a higher need for 
insulin due to major surgery, serious illness or infection. See also section 4. 
In addition to this leaflet, a patient alert card is included in the packaging which contains important 
safety information that you need before and during treatment with Zynquista. Your doctor will 
schedule a dedicated education session, to discuss the risk of DKA, how to recognize DKA risk 
factors, signs or symptoms, how and when to monitor ketone levels and what actions to take when 
ketone levels are elevated. 
 
Talk to your doctor, pharmacist or nurse before taking Zynquista, and during treatment: 
• if you have the following symptoms, which may be a sign of a serious condition, diabetic 

ketoacidosis (see also section 4): 
o nausea, vomiting, or abdominal pain  
o excessive thirst  
o constantly feeling tired  
o high levels of ketones in urine tests or beta-hydroxybutyrate (BHB) in blood tests  
o difficulty breathing/rapid, deep breathing  
o breath with fruity odour  
o difficulty paying attention, or confusion  
o rapid weight loss  

• if you have an acute medical illness or surgery 
• if you have no access to ketone testing materials or no immediate access to a doctor if blood or 

urine ketones are elevated 
• if you are using a low dose of insulin 
• if you are on caloric restriction, carbohydrate restriction or ketogenic diet  
• if you had a recent or recurrent history of diabetic ketoacidosis (e.g. 1 episode in the past 3 months 

or more than 1 episode in the past 6 months) 
• if you have kidney problems  
• if you have liver problems  
• if you have an infection of the kidney or the urinary tract. Your doctor may ask you to stop taking 

Zynquista until you have recovered 
• if you have a history of chronic or recurrent yeast infections of the genitals (thrush)  
• if you might be at risk of dehydration (for example, if you are taking medicines that increase urine 

production [diuretics] or lower blood pressure or if you are over 65 years old). Ask about ways to 
prevent dehydration. 

• if you develop a combination of symptoms of pain, tenderness, redness, or swelling of the genitals 
or the area between the genitals and the anus with fever or feeling generally unwell. These 
symptoms could be a sign of a rare but serious or even life-threatening infection, called 
necrotizing fasciitis of the perineum or Fournier’s gangrene which destroys the tissue under the 
skin. Fournier´s gangrene has to be treated immediately. 

 
Foot care 
For all patients with diabetes it is important to check your feet regularly and follow any other advice 
on foot care from your doctor or nurse. 
 
Urine glucose 
Because of how Zynquista works, your urine will test positive for sugar while you are on this 
medicine. 
 
Children and adolescents 
Zynquista is not recommended for children and adolescents under 18 years of age, because it has not 
been studied in these patients. 
 
Other medicines and Zynquista 
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 
medicines.  



42 

In particular, tell your doctor if you are taking any of the following medicines: 
• digoxin or digitoxin (medicines used for heart problems). The level of digoxin or digitoxin in your 

blood may need to be checked if you take these medicines with Zynquista. 
• phenytoin or phenobarbital (epilepsy medicines used to control fits) 
• ritonavir (a medicine used to treat HIV infection) 
• rifampicin (an antibiotic used to treat tuberculosis and some other infections). 
 
As sotagliflozin is taken together with insulin, hypoglycaemia may occur during treatment. 
Your doctor may reduce the dose of insulin. 
 
Pregnancy and breast-feeding  
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. Talk to your doctor about the best 
way to control your blood sugar while you are pregnant. Zynquista should not be used during the last 
six months of pregnancy. 
 
Talk to your doctor before taking this medicine if you would like to breast-feed or if you are breast-
feeding. It is not known if this medicine passes into breast milk. You should not take this medicine if 
you are breast-feeding. 
 
Driving and using machines 
Zynquista is not likely to affect your ability to drive and use machines. However, Zynquista is taken 
with insulin,  which can cause your blood sugar levels to fall too low (hypoglycaemia) resulting in 
symptoms such as shaking, sweating and change in vision, and this may affect your ability to drive 
and use machines. Do not drive or use any tools or machines, if you feel dizzy during diabetes 
treatment. 
 
 
3. How to take Zynquista 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or 
nurse if you are not sure.  
 
How much to take 
The recommended dose of Zynquista is one 200-mg tablet once a day before the first meal of the day. 
Your doctor will decide whether to increase your dose to 400 mg once a day. 
Your doctor will prescribe the dose that is right for you. Do not change your dose unless your doctor 
has told you to. 
 
Taking this medicine 
• Zynquista should be taken once daily by mouth.  
• The tablet should be taken before the first meal of the day 
• Follow your doctor’s instructions about insulin dose while taking Zynquista. 
 
Your doctor will prescribe Zynquista together with insulin treatment to lower the amount of sugar in 
your blood. Follow your doctor’s instructions on taking these other medicine(s) to achieve the best 
results for your health. 
 
If you take more Zynquista than you should 
If you take more Zynquista tablets than you should, talk to a doctor or go to a hospital immediately. 
Take the medicine pack with you. 
 
If you forget to take Zynquista 
If a dose is missed, it should be taken as soon as you remember the missed dose.  
Do not take a double dose of Zynquista o make up the forgotten dose. 
 
If you stop taking Zynquista 



43 

Do not stop taking Zynquista without first checking with your doctor. Your blood sugar levels may 
increase when you stop taking Zynquista. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.  
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Contact a doctor or the nearest hospital straight away if you have any of the following side 
effects: 
 
Diabetic ketoacidosis (DKA), seen commonly (may affect up to 1 in 100 people) 
These are the signs and symptoms of diabetic ketoacidosis (see also section 2 under ‘Warnings and 
precautions’): 
o nausea, vomiting, or abdominal pain  
o excessive thirst  
o constantly feeling tired  
o high levels of ketones in urine tests or beta-hydroxybutyrate (BHB) in blood tests  
o difficulty breathing/rapid, deep breathing  
o breath with fruity odour  
o difficulty paying attention, or confusion  
o rapid weight loss. 
 
While treated with Zynquista the risk of DKA is increased and may occur with low, normal or high 
blood glucose level. Check your ketones regularly during the first two weeks after starting Zynquista. 
If you have any of these symptoms, or if you are in a situation that could increase your risk for DKA, 
you must check your ketones, either in the blood or in the urine. If you are using an insulin pump, 
monitor your ketones levels three to four hours after changing pump materials. 
In case of a potential DKA or elevated ketone levels are elevated contact your doctor immediately or 
go to the nearest hospital right away.  The doctor may decide to temporarily stop the treatment with 
Zynquista. 
During a dedicated session your doctor may schedule, discuss how to manage elevated ketone levels to 
prevent DKA (see section 2). 
 
Make sure you carry the Patient Alert Card, that was given to you by your physician and that is also 
enclosed in the product packaging, with you at all times. Share it with all of your doctors, nurses or 
pharmacists when you need any treatment. You can also get the Patient Alert Card by scanning the QR 
code or by visiting the website below: 
 
Other side effects: 
Very common (may affect more than 1 in 10 people) 
• yeast infection (thrush) of the vagina (signs may include irritation, itching, unusual discharge or 

odour)  
 
Common (may affect more than 1 in 100 people) 
• diarrhoea 
• raised ketone levels in your blood  
• yeast infection (thrush) of the penis (signs may include irritation, itching, unusual discharge or 

odour)  
• passing more urine than usual or needing to pass it more often 
• urinary tract infection, signs include burning sensation when passing urine, urine that appears 

cloudy, pain in the pelvis, or mid back pain (when kidneys are infected) 
• dehydration (losing too much water from your body, symptoms include dry mouth, feeling dizzy, 

light-headed, or weak, especially when you stand up, fainting) 
• flatulence 



44 

• blood tests may show increase in the amount of bad cholesterol (called LDL - a type of fat in your 
blood) 

• blood tests may show increase in the amount of red blood cells in your blood (called haematocrit) 
• blood tests may show increase related to kidney function (such as ‘creatinine’). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
5. How to store Zynquista 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton after “EXP”. 
The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer used. These measures will help protect the environment.  
 
 
6. Contents of the pack and other information 
 
What Zynquista contains 
• The active substance is sotagliflozin. 
Each tablet contains 200 mg sotagliflozin.  
• The other ingredients are: 

- tablet core: microcrystalline cellulose (E460i), croscarmellose sodium, colloidal anhydrous 
silica; magnesium stearate; talc. 

- film-coating: poly(vinyl alcohol); macrogol; titanium dioxide (E 171); talc; indigo carmine 
aluminium lake (E132). 

- Printing ink: shellac; iron oxide black (E172); propylene glycol. 
  
What Zynquista looks like and contents of the pack 
 
Zynquista 200 mg film-coated tablets (tablets) are oval, blue, with “2456” on one side printed in black 
ink (tablet length: 14.2 mm, tablet width: 8.7 mm). 
Zynquista is available in PVC/PCTFE/Aluminium opaque blisters.  
Pack sizes of 10, 20, 30, 60, 90, 100, 180 film-coated tablets, and a multipack of 200 film-coated 
tablets (2 packs of 100 film-coated tablets). 
 
Not all pack sizes may be marketed. 
  
Marketing Authorisation Holder and Manufacturer 
Marketing Authorisation Holder:  
Navigant Germany GmbH 
Albrechtstr. 10c  
10117 Berlin 
Germany 
 
Manufacturer : 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


45 

Sanofi Winthrop Industrie 
1, rue de la Vierge 
Ambarès et Lagrave 
F – 33565 Carbon Blanc 
France 
 
 
This leaflet was last revised in. 
 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 

http://www.ema.europa.eu/
http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET