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

Diabetes Mellitus, Type 2 Clinical Trial

— SUSTAIN™ 2  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01930188
• Other study ID #: NN9535-3626
• Secondary ID: 2012-004827-19U1
• Status: Completed
• Phase: Phase 3
• Start date: December 2, 2013
• Est. completion date: October 12, 2015

Study information

• Verified date: May 2019
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1231
• Est. completion date: October 12, 2015
• Est. primary completion date: October 12, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• semaglutide
For subcutaneous injection (s.c., under the skin) once weekly. Will follow a fixed dose escalation regimen. The trial drug will be added on to the subject's stable pre-trial medication.
• sitagliptin
Tablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.
• placebo
Tablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.
• placebo
For subcutaneous injection (s.c., under the skin) once weekly. Will follow a fixed dose escalation regimen. The trial drug will be added on to the subject's stable pre-trial medication.

Locations

Country	Name	City	State
Argentina	Novo Nordisk Investigational Site	Buenos Aires
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Mar del Plata
Bulgaria	Novo Nordisk Investigational Site	Burgas
Bulgaria	Novo Nordisk Investigational Site	Haskovo
Bulgaria	Novo Nordisk Investigational Site	Petrich
Bulgaria	Novo Nordisk Investigational Site	Ruse
Bulgaria	Novo Nordisk Investigational Site	Sliven
Bulgaria	Novo Nordisk Investigational Site	Smolyan
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Stara Zagora
Bulgaria	Novo Nordisk Investigational Site	Vratsa
Czechia	Novo Nordisk Investigational Site	Chrudim
Czechia	Novo Nordisk Investigational Site	Ostrava
Czechia	Novo Nordisk Investigational Site	Plzen
Czechia	Novo Nordisk Investigational Site	Praha 4- Chodov
Czechia	Novo Nordisk Investigational Site	Praha 5
Hong Kong	Novo Nordisk Investigational Site	Shatin, New Territories
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Debrecen
Hungary	Novo Nordisk Investigational Site	Szeged
Hungary	Novo Nordisk Investigational Site	Szombathely
India	Novo Nordisk Investigational Site	Ahmedabad	Gujarat
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Bhubaneswar	Orissa
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Indore	Madhya Pradesh
India	Novo Nordisk Investigational Site	Jaipur	Rajasthan
India	Novo Nordisk Investigational Site	Kochi	Kerala
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Kozhikode	Kerala
India	Novo Nordisk Investigational Site	Ludhiana	Punjab
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	New Delhi
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Trivandrum	Kerala
Japan	Novo Nordisk Investigational Site	Asahikawa-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Ibaraki
Japan	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka
Japan	Novo Nordisk Investigational Site	Kitakyushu-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Mitaka-shi, Tokyo
Japan	Novo Nordisk Investigational Site	Mito-shi, Ibaraki
Japan	Novo Nordisk Investigational Site	Miyazaki
Japan	Novo Nordisk Investigational Site	Okayama-shi, Okayama
Japan	Novo Nordisk Investigational Site	Osaka
Japan	Novo Nordisk Investigational Site	Osaka-shi, Osaka
Japan	Novo Nordisk Investigational Site	Osaka-shi, Osaka
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Mexico	Novo Nordisk Investigational Site	Aguascalientes
Mexico	Novo Nordisk Investigational Site	Aguascalientes
Mexico	Novo Nordisk Investigational Site	Guadalajara	Jalisco
Mexico	Novo Nordisk Investigational Site	Monterrey	Nuevo León
Mexico	Novo Nordisk Investigational Site	Pachuca	Hidalgo
Norway	Novo Nordisk Investigational Site	Ålesund
Norway	Novo Nordisk Investigational Site	Hamar
Norway	Novo Nordisk Investigational Site	Kløfta
Norway	Novo Nordisk Investigational Site	Kongsvinger
Norway	Novo Nordisk Investigational Site	Stavanger
Portugal	Novo Nordisk Investigational Site	Almada
Portugal	Novo Nordisk Investigational Site	Coimbra
Portugal	Novo Nordisk Investigational Site	Lisboa
Portugal	Novo Nordisk Investigational Site	Lisboa
Portugal	Novo Nordisk Investigational Site	Matosinhos
Portugal	Novo Nordisk Investigational Site	Tomar
Portugal	Novo Nordisk Investigational Site	Viana do Castelo
Portugal	Novo Nordisk Investigational Site	Vila Nova de Gaia
Romania	Novo Nordisk Investigational Site	Baia Mare	Maramures
Romania	Novo Nordisk Investigational Site	Brasov
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Ploiesti	Prahova
Russian Federation	Novo Nordisk Investigational Site	Barnaul
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Nizhniy Novgorod
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Samara
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Smolensk
Russian Federation	Novo Nordisk Investigational Site	Tomsk
Russian Federation	Novo Nordisk Investigational Site	Tumen
Russian Federation	Novo Nordisk Investigational Site	Ufa
Russian Federation	Novo Nordisk Investigational Site	Volgograd
Russian Federation	Novo Nordisk Investigational Site	Voronezh
Russian Federation	Novo Nordisk Investigational Site	Yaroslavl
South Africa	Novo Nordisk Investigational Site	Bloemfontein	Free State
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	East London	Eastern Cape
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Krugersdorp	Gauteng
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
Spain	Novo Nordisk Investigational Site	Almería
Spain	Novo Nordisk Investigational Site	Centelles (Barcelona)
Spain	Novo Nordisk Investigational Site	La Coruña
Spain	Novo Nordisk Investigational Site	La Roca del Vallés
Spain	Novo Nordisk Investigational Site	Lleida
Spain	Novo Nordisk Investigational Site	Palma de Mallorca
Spain	Novo Nordisk Investigational Site	Sevilla
Sweden	Novo Nordisk Investigational Site	Kristianstad
Sweden	Novo Nordisk Investigational Site	Lund
Sweden	Novo Nordisk Investigational Site	Malmö
Sweden	Novo Nordisk Investigational Site	Stockholm
Thailand	Novo Nordisk Investigational Site	Bangkok
Thailand	Novo Nordisk Investigational Site	Bangkok
Thailand	Novo Nordisk Investigational Site	Bangkoknoi, Bangkok
Thailand	Novo Nordisk Investigational Site	Nakhon Ratchasima
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Antalya
Turkey	Novo Nordisk Investigational Site	Çorum
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Konya
Turkey	Novo Nordisk Investigational Site	Rize
Turkey	Novo Nordisk Investigational Site	Trabzon
Ukraine	Novo Nordisk Investigational Site	Cherkasy
Ukraine	Novo Nordisk Investigational Site	Ivano-Frankivsk
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Odesa
Ukraine	Novo Nordisk Investigational Site	Vinnytsia
Ukraine	Novo Nordisk Investigational Site	Zaporizhia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

Argentina,  Bulgaria,  Czechia,  Hong Kong,  Hungary,  India,  Japan,  Mexico,  Norway,  Portugal,  Romania,  Russian Federation,  South Africa,  Spain,  Sweden,  Thailand,  Turkey,  Ukraine, 

References & Publications (11)

Ahrén 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 O — View 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

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). eP

Ahrén B, Masmiquel L, Kumar H, Sargin M, Karsbøl 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 — View Citation

Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jódar 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 tri — View 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. — View 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 — View Citation

Fonseca VA, Capehorn MS, Garg SK, Jódar 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 Apr 2. pii: jc.2018-02685. doi: 10.1210/jc.2018-02685. [Epub ahead of print] — View 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. — View Citation

Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HBA(1C) =1.0% AND WEIGHT =5.0% WITH SEMAGLUTIDE VS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Mar 13. doi: 10.4158/EP-2018-0444. [Epub ahead of print] — View 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 a — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c (Glycosylated Haemoglobin) From Baseline	Change in HbA1c from baseline until week 56.Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of randomised semaglutide or sitagliptin.	Week 0, week 56
Secondary	Change in Body Weight From Baseline	Change in body weight from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin.	Week 0, week 56
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline	Change in fasting plasma glucose from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin.	Week 0, week 56
Secondary	Change in Systolic and Diastolic Blood Pressure From Baseline	Change in systolic and diastolic blood pressure from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin	Week 0, week 56
Secondary	Change in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) From Baseline	Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin. The DTSQs questionnaire was used to assess subjects' treatment satisfaction. This questionnaire contained 8 components and evaluates the diabetes treatment (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings towards the treatment. The result presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction.	Week 0, week 56
Secondary	Subjects Who Achieved HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target (Yes/no)	Subjects who achieved HbA1c =6.5% (48 mmol/mol) American Association of Clinical Endocrinologists (AACE) target (yes/no) after week 56 weeks of treatment.	After 56 weeks treatment

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