DiabetesPhase 3SUSTAIN™ 2NCT01930188

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

A Phase 3 study testing semaglutide and sitagliptin in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 141 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetes, Diabetes Mellitus, Type 2
What is being tested?: semaglutide and sitagliptin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,231 participants
Where: 141 sitesin 18 countries
Study dates: 2 Dec 2013to 12 Oct 2015
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

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

Trial locations and contacts

141 sites in 18 countries.

Country

City, postcode or hospital

141 sites in 18 countries

India19 sites

Novo Nordisk Investigational Site
Ahmedabad, Gujarat, 380006
Novo Nordisk Investigational Site
Bangalore, Karnataka, 560034
Novo Nordisk Investigational Site
Bangalore, Karnataka, 560054
Novo Nordisk Investigational Site
Bhubaneswar, Odisha, 751019
Novo Nordisk Investigational Site
Chennai, Tamil Nadu, 600116
Novo Nordisk Investigational Site
Hyderabad, Andhra Pradesh, 500003
Novo Nordisk Investigational Site
Indore, Madhya Pradesh, 452010
Novo Nordisk Investigational Site
Jaipur, Rajasthan, 302004
Novo Nordisk Investigational Site
Kochi, Kerala, 682041
Novo Nordisk Investigational Site
Kolkata, West Bengal, 700020
Novo Nordisk Investigational Site
Kolkata, West Bengal, 700054
Novo Nordisk Investigational Site
Kozhikode, Kerala, 673017
Novo Nordisk Investigational Site
Ludhiana, Punjab, 141001
Novo Nordisk Investigational Site
Mumbai, Maharashtra, 400008
Novo Nordisk Investigational Site
New Delhi, 110017
Novo Nordisk Investigational Site
Pune, Maharashtra, 411001
Novo Nordisk Investigational Site
Pune, Maharashtra, 411004
Novo Nordisk Investigational Site
Pune, Maharashtra, 411040
Novo Nordisk Investigational Site
Trivandrum, Kerala, 695011

Other trials in India

Russia19 sites

Novo Nordisk Investigational Site
Barnaul, 656024
Novo Nordisk Investigational Site
Moscow, 115478
Novo Nordisk Investigational Site
Moscow, 117036
Novo Nordisk Investigational Site
Moscow, 119435
Novo Nordisk Investigational Site
Moscow, 125367
Novo Nordisk Investigational Site
Moscow
Novo Nordisk Investigational Site
Nizhny Novgorod, 603011
Novo Nordisk Investigational Site
Novosibirsk, 630047
Novo Nordisk Investigational Site
Novosibirsk, 630099
Novo Nordisk Investigational Site
Saint Petersburg, 197762
Novo Nordisk Investigational Site
Samara, 443041
Novo Nordisk Investigational Site
Saratov, 410018
Novo Nordisk Investigational Site
Smolensk, 214019
Novo Nordisk Investigational Site
Tomsk, 634063
Novo Nordisk Investigational Site
Tyumen, 625023
Novo Nordisk Investigational Site
Ufa, 450083
Novo Nordisk Investigational Site
Volgograd, 400138
Novo Nordisk Investigational Site
Voronezh, 394018
Novo Nordisk Investigational Site
Yaroslavl, 150003

Other trials in Russia

Japan14 sites

Novo Nordisk Investigational Site
Asahikawa-shi, Hokkaido, 070-0002
Novo Nordisk Investigational Site
Ibaraki, 311-0113
Novo Nordisk Investigational Site
Kashiwara-shi, Osaka, 582-0005
Novo Nordisk Investigational Site
Kitakyushu-shi, Fukuoka, 800 0252
Novo Nordisk Investigational Site
Mitaka-shi, Tokyo, 181-0013
Novo Nordisk Investigational Site
Mito-shi, Ibaraki, 310-0826
Novo Nordisk Investigational Site
Miyazaki, 880-0034
Novo Nordisk Investigational Site
Okayama-shi, Okayama, 700 8505
Novo Nordisk Investigational Site
Osaka, 569-1045
Novo Nordisk Investigational Site
Osaka-shi, Osaka, 532 0003
Novo Nordisk Investigational Site
Osaka-shi, Osaka
Novo Nordisk Investigational Site
Sapporo-shi, Hokkaido, 060-0001
Novo Nordisk Investigational Site
Tokyo, 103-0027
Novo Nordisk Investigational Site
Tokyo, 125-0054

Other trials in Japan

Turkey (Türkiye)12 sites

Novo Nordisk Investigational Site
Ankara, 06110
Novo Nordisk Investigational Site
Antalya, 07058
Novo Nordisk Investigational Site
Çorum, 19200
Novo Nordisk Investigational Site
Istanbul, 34303
Novo Nordisk Investigational Site
Istanbul, 34371
Novo Nordisk Investigational Site
Istanbul, 34718
Novo Nordisk Investigational Site
Istanbul, 34722
Novo Nordisk Investigational Site
Istanbul, 34752
Novo Nordisk Investigational Site
Istanbul, 34890
Novo Nordisk Investigational Site
Konya, 42090
Novo Nordisk Investigational Site
Rize, 53020
Novo Nordisk Investigational Site
Trabzon, 61040

Other trials in Turkey (Türkiye)

Bulgaria10 sites

Novo Nordisk Investigational Site
Burgas, 8000
Novo Nordisk Investigational Site
Haskovo, 6300
Novo Nordisk Investigational Site
Petrich, 2850
Novo Nordisk Investigational Site
Rousse, 7000
Novo Nordisk Investigational Site
Sliven, 8800
Novo Nordisk Investigational Site
Smolyan, 4700
Novo Nordisk Investigational Site
Sofia, 1233
Novo Nordisk Investigational Site
Sofia, 1336
Novo Nordisk Investigational Site
Stara Zagora, 6000
Novo Nordisk Investigational Site
Vratsa, 3001

Other trials in Bulgaria

Portugal8 sites

Novo Nordisk Investigational Site
Almada, 2805-267
Novo Nordisk Investigational Site
Coimbra, 3046-853
Novo Nordisk Investigational Site
Lisbon, 1250-230
Novo Nordisk Investigational Site
Lisbon, 1500-650
Novo Nordisk Investigational Site
Matosinhos Municipality, 4464-513
Novo Nordisk Investigational Site
Tomar, 2304-909
Novo Nordisk Investigational Site
Viana do Castelo, 4901-858
Novo Nordisk Investigational Site
Vila Nova de Gaia, 4434-502

Other trials in Portugal

South Africa8 sites

Novo Nordisk Investigational Site
Bloemfontein, Free State, 9301
Novo Nordisk Investigational Site
Durban, KwaZulu-Natal, 4001
Novo Nordisk Investigational Site
Durban, KwaZulu-Natal, 4092
Novo Nordisk Investigational Site
East London, Eastern Cape, 5201
Novo Nordisk Investigational Site
Johannesburg, Gauteng, 2001
Novo Nordisk Investigational Site
Krugersdorp, Gauteng, 1739
Novo Nordisk Investigational Site
Pretoria, Gauteng, 0002
Novo Nordisk Investigational Site
Pretoria, Gauteng, 0084

Other trials in South Africa

Spain7 sites

Novo Nordisk Investigational Site
A Coruña, 15006
Novo Nordisk Investigational Site
Almería, 04001
Novo Nordisk Investigational Site
Centelles (Barcelona), 08540
Novo Nordisk Investigational Site
La Roca Del Vallés, 08430
Novo Nordisk Investigational Site
Lleida, 25198
Novo Nordisk Investigational Site
Palma de Mallorca, 07010
Novo Nordisk Investigational Site
Seville, 41003

Other trials in Spain

Ukraine6 sites

Novo Nordisk Investigational Site
Cherkasy, 18009
Novo Nordisk Investigational Site
Ivano-Frankivsk, 76018
Novo Nordisk Investigational Site
Kyiv, 04114
Novo Nordisk Investigational Site
Odesa, 65114
Novo Nordisk Investigational Site
Vinnytsia, 21010
Novo Nordisk Investigational Site
Zaporizhia, 69600

Other trials in Ukraine

Czechia5 sites

Novo Nordisk Investigational Site
Chrudim, 537 01
Novo Nordisk Investigational Site
Ostrava, 707 02
Novo Nordisk Investigational Site
Pilsen, 304 60
Novo Nordisk Investigational Site
Prague, 150 00
Novo Nordisk Investigational Site
Praha 4- Chodov, 149 00

Other trials in Czechia

Hungary5 sites

Novo Nordisk Investigational Site
Budapest, 1076
Novo Nordisk Investigational Site
Budapest, H-1134
Novo Nordisk Investigational Site
Debrecen, 4043
Novo Nordisk Investigational Site
Szeged, H-6720
Novo Nordisk Investigational Site
Szombathely, H-9700

Other trials in Hungary

Mexico5 sites

Novo Nordisk Investigational Site
Aguascalientes, 20129
Novo Nordisk Investigational Site
Aguascalientes, 20230
Novo Nordisk Investigational Site
Guadalajara, Jalisco, 44670
Novo Nordisk Investigational Site
Monterrey, Nuevo León, 64620
Novo Nordisk Investigational Site
Pachuca, Hidalgo, 42084

Other trials in Mexico

Norway5 sites

Novo Nordisk Investigational Site
Ålesund, 6003
Novo Nordisk Investigational Site
Hamar, 2317
Novo Nordisk Investigational Site
Kløfta, 2040
Novo Nordisk Investigational Site
Kongsvinger, 2212
Novo Nordisk Investigational Site
Stavanger, 4005

Other trials in Norway

Romania5 sites

Novo Nordisk Investigational Site
Baia Mare, Maramureş, 430123
Novo Nordisk Investigational Site
Brasov, 500365
Novo Nordisk Investigational Site
Bucharest, 020359
Novo Nordisk Investigational Site
Bucharest, 022441
Novo Nordisk Investigational Site
Ploieşti, Prahova, 100342

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Argentina4 sites

Novo Nordisk Investigational Site
Buenos Aires, C1425AGC
Novo Nordisk Investigational Site
CABA, C1179AAB
Novo Nordisk Investigational Site
CABA
Novo Nordisk Investigational Site
Mar del Plata, B7600GNY

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Sweden4 sites

Novo Nordisk Investigational Site
Kristianstad, 291 85
Novo Nordisk Investigational Site
Lund, 222 22
Novo Nordisk Investigational Site
Malmö, 205 02
Novo Nordisk Investigational Site
Stockholm, 113 24

Other trials in Sweden

Thailand4 sites

Novo Nordisk Investigational Site
Bangkok, 10330
Novo Nordisk Investigational Site
Bangkok, 10400
Novo Nordisk Investigational Site
Bangkoknoi, Bangkok, 10700
Novo Nordisk Investigational Site
Nakhon Ratchasima, 30000

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Hong Kong1 site

Novo Nordisk Investigational Site
Shatin, New Territories

Other trials in Hong Kong

About this study

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)

Conditions: Diabetes, Diabetes Mellitus, Type 2
Being tested: semaglutide, sitagliptin, placebo
Medical subject headings: Diabetes Mellitus, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

semaglutideDrug
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.
sitagliptinDrug
Tablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.
placeboDrug
Tablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.
placeboDrug
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.

Study groups in NCT01930188
Study group	Role	What they receive
Semaglutide 0.5 mg + sitagliptin placebo	Experimental	Not described Receives: Drug: semaglutide; Drug: placebo
Semaglutide 1.0 mg + sitagliptin placebo	Experimental	Not described Receives: Drug: semaglutide; Drug: placebo
Sitagliptin 100 mg + semaglutide placebo 1.0 mg	Active comparator	Not described Receives: Drug: sitagliptin; Drug: placebo
Sitagliptin 100 mg + semaglutide placebo 0.5 mg	Active comparator	Not described Receives: Drug: sitagliptin; Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Week 0, week 56

Secondary outcomes (5)

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.
Measured: Week 0, week 56
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.
Measured: Week 0, week 56
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
Measured: Week 0, week 56
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.
Measured: Week 0, week 56
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.
Measured: After 56 weeks treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Dec 201312 Oct 2015

First posted28 Aug 2013 (estimated)
Study start2 Dec 2013
Primary completion12 Oct 2015
Study completion12 Oct 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (18)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 1,231 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01930188
Sponsor's protocol ID: NN9535-3626
Other IDs: 2012-004827-19, U1111-1135-8730, 132366, CTRI/2014/05/004626
Acronym: SUSTAIN™ 2
Status last verified: May 2019
First submitted: 23 Aug 2013
Last updated: 13 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Fonseca VA, Capehorn MS, Garg SK, Jodar Gimeno E, Hansen OH, Holst AG, Nayak G, Seufert J. Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide. J Clin Endocrinol Metab. 2019 Sep 1;104(9):4078-4086. doi: 10.1210/jc.2018-02685.
PubMed 30938762
Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA1C >/=1.0% AND WEIGHT >/=5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13.
PubMed 30865526
Ahrén B, Comas LM, Kumar H, Sargin M, Derving Karsbøl J, Jacobsen SH, Chow F. Efficacy and Safety of Once-weekly Semaglutide vs Sitagliptin as add-on to Metformin and/or Thiazolidinediones After 56 Weeks in Subjects With Type 2 Diabetes (SUSTAIN 2). Oral Presentation 12 Jun 2016 at American Diabetes Association - 76th Annual Scientific Sessions.
Ahrén B, Masmiquel L, Kumar H, Sargin M, Derving Karsbøl J, Jacobsen SH, Chow F. Efficacy and Safety of Once-weekly Semaglutide vs Sitagliptin as add-on to Metformin and/or Thiazolidinediones After 56 Weeks in Subjects With Type 2 Diabetes (SUSTAIN 2). ePoster #767 presented 12 Sep 2016 at European Association for the Study of Diabetes - 52nd Annual Meeting.
Ahren B, Masmiquel L, Kumar H, Sargin M, Karsbol JD, Jacobsen SH, Chow F. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 2017 May;5(5):341-354. doi: 10.1016/S2213-8587(17)30092-X. Epub 2017 Apr 3.
PubMed 28385659
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.
PubMed 29748996
Ahren B, Atkin SL, Charpentier G, Warren ML, Wilding JPH, Birch S, Holst AG, Leiter LA. Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2210-2219. doi: 10.1111/dom.13353. Epub 2018 Jun 12.
PubMed 29766634
Sharma R, Wilkinson L, Vrazic H, Popoff E, Lopes S, Kanters S, Druyts E. Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review and network meta-analysis. Curr Med Res Opin. 2018 Sep;34(9):1595-1603. doi: 10.1080/03007995.2018.1476332. Epub 2018 May 29.
PubMed 29764222
DeVries JH, Desouza C, Bellary S, Unger J, Hansen OKH, Zacho J, Woo V. Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. Diabetes Obes Metab. 2018 Oct;20(10):2426-2434. doi: 10.1111/dom.13396. Epub 2018 Jul 9.
PubMed 29862621
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.
PubMed 29907893
Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jodar E, Mehta R, Woo V, Lingvay I. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019 Oct;45(5):409-418. doi: 10.1016/j.diabet.2018.12.001. Epub 2019 Jan 4.
PubMed 30615985
Pulleyblank R, Larsen NB. Cost-Effectiveness of Semaglutide vs. Empagliflozin, Canagliflozin, and Sitagliptin for Treatment of Patients with Type 2 Diabetes in Denmark: A Decision-Analytic Modelling Study. Pharmacoecon Open. 2023 Jul;7(4):579-591. doi: 10.1007/s41669-023-00416-z. Epub 2023 May 13.
PubMed 37178435
Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.
PubMed 32998732
Lingvay I, Capehorn MS, Catarig AM, Johansen P, Lawson J, Sandberg A, Shaw R, Paine A. Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis. J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4593-604. doi: 10.1210/clinem/dgaa577.
PubMed 32827435
Capehorn M, Ghani Y, Hindsberger C, Johansen P, Jodar E. Once-Weekly Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2-4 and 10. Diabetes Ther. 2020 May;11(5):1061-1075. doi: 10.1007/s13300-020-00796-z. Epub 2020 Mar 19.
PubMed 32193837

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 13 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01930188
Acronym / sponsor ID: SUSTAIN™ 2 / NN9535-3626
Conditions: Diabetes, Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,231 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: 2 Dec 2013 (actual)
Primary completion: 12 Oct 2015 (actual)
Study completion: 12 Oct 2015 (actual)
First posted: 28 Aug 2013 (estimated)
Results: Posted 7 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Semaglutide 0.5 mg + sitagliptin placebo	Experimental	Drug: semaglutide, Drug: placebo
Semaglutide 1.0 mg + sitagliptin placebo	Experimental	Drug: semaglutide, Drug: placebo
Sitagliptin 100 mg + semaglutide placebo 1.0 mg	Active comparator	Drug: sitagliptin, Drug: placebo
Sitagliptin 100 mg + semaglutide placebo 0.5 mg	Active comparator	Drug: sitagliptin, Drug: placebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
semaglutideFor 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.	Drug	Semaglutide 0.5 mg + sitagliptin placebo, Semaglutide 1.0 mg + sitagliptin placebo
sitagliptinTablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.	Drug	Sitagliptin 100 mg + semaglutide placebo 0.5 mg, Sitagliptin 100 mg + semaglutide placebo 1.0 mg
placeboTablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.	Drug	Semaglutide 0.5 mg + sitagliptin placebo, Semaglutide 1.0 mg + sitagliptin placebo
placeboFor 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.	Drug	Sitagliptin 100 mg + semaglutide placebo 0.5 mg, Sitagliptin 100 mg + semaglutide placebo 1.0 mg

Primary outcome

Change in HbA1c (Glycosylated Haemoglobin) From Baseline
Time frame: Week 0, week 56
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.

5 secondary outcomes

Change in Body Weight From Baseline
Time frame: Week 0, week 56
Change in Fasting Plasma Glucose (FPG) From Baseline
Time frame: Week 0, week 56
Change in Systolic and Diastolic Blood Pressure From Baseline
Time frame: Week 0, week 56
Change in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) From Baseline
Time frame: Week 0, week 56
Subjects Who Achieved HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target (Yes/no)
Time frame: After 56 weeks treatment

Results and safety

Results posted to the registry on 7 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Semaglutide 0.5 mg + Sitagliptin Placebo	409	387
Semaglutide 1.0 mg + Sitagliptin Placebo	409	388
Sitagliptin + Semaglutide Placebo	407	388

Primary outcome: Change in HbA1c (Glycosylated Haemoglobin) From Baseline

Time frame: Week 0, week 56. Least squares mean (Standard Error). Unit: percentage of glycosylated haemoglobin

Measure	Semaglutide 0.5 mg + Sitagliptin Placebo n = 409	Semaglutide 1.0 mg + Sitagliptin Placebo n = 409	Sitagliptin + Semaglutide Placebo n = 407
Value	-1.32 (0.05)	-1.61 (0.05)	-0.55 (0.05)

Semaglutide 1.0 mg + Sitagliptin Placebo vs Sitagliptin + Semaglutide Placebo: treatment difference: -1.06 (95% CI -1.21 to -0.91), p <0.0001, Mixed Models Analysis
Semaglutide 0.5 mg + Sitagliptin Placebo vs Sitagliptin + Semaglutide Placebo: treatment difference: -0.92 (95% CI -1.21 to -0.62), p <0.0001, Mixed Models Analysis

Population analysed: Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events are reported for on-treatment period i.e from the date of initiation of trial product to the end of the on-treatment period (up to 56 weeks).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Semaglutide 1.0 mg + Sitagliptin Placebo	30 of 409 (7.3%)	197 of 409 (48.2%)	Not reported
Semaglutide 0.5 mg + Sitagliptin Placebo	30 of 409 (7.3%)	208 of 409 (50.9%)	Not reported
Sitagliptin 100 mg + Semaglutide Placebo 1.0 mg	13 of 204 (6.4%)	75 of 204 (36.8%)	Not reported
Sitagliptin 100 mg + Semaglutide Placebo 0.5 mg	16 of 203 (7.9%)	85 of 203 (41.9%)	Not reported

Limitations and caveats (from the sponsor): None reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 30938762Fonseca VA, Capehorn MS, Garg SK, Jodar Gimeno E, Hansen OH, Holst AG, Nayak G, Seufert J. Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide. J Clin Endocrinol Metab. 2019 Sep 1;104(9):4078-4086. doi: 10.1210/jc.2018-02685.
Background: PubMed 30865526Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA1C >/=1.0% AND WEIGHT >/=5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13.
Results publicationAhrén B, Comas LM, Kumar H, Sargin M, Derving Karsbøl J, Jacobsen SH, Chow F. Efficacy and Safety of Once-weekly Semaglutide vs Sitagliptin as add-on to Metformin and/or Thiazolidinediones After 56 Weeks in Subjects With Type 2 Diabetes (SUSTAIN 2). Oral Presentation 12 Jun 2016 at American Diabetes Association - 76th Annual Scientific Sessions.
Results publicationAhrén B, Masmiquel L, Kumar H, Sargin M, Derving Karsbøl J, Jacobsen SH, Chow F. Efficacy and Safety of Once-weekly Semaglutide vs Sitagliptin as add-on to Metformin and/or Thiazolidinediones After 56 Weeks in Subjects With Type 2 Diabetes (SUSTAIN 2). ePoster #767 presented 12 Sep 2016 at European Association for the Study of Diabetes - 52nd Annual Meeting.
Results publication: PubMed 28385659Ahren B, Masmiquel L, Kumar H, Sargin M, Karsbol JD, Jacobsen SH, Chow F. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 2017 May;5(5):341-354. doi: 10.1016/S2213-8587(17)30092-X. Epub 2017 Apr 3.
Results publication: PubMed 29748996Petri 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.
Results publication: PubMed 29766634Ahren B, Atkin SL, Charpentier G, Warren ML, Wilding JPH, Birch S, Holst AG, Leiter LA. Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2210-2219. doi: 10.1111/dom.13353. Epub 2018 Jun 12.
Results publication: PubMed 29764222Sharma R, Wilkinson L, Vrazic H, Popoff E, Lopes S, Kanters S, Druyts E. Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review and network meta-analysis. Curr Med Res Opin. 2018 Sep;34(9):1595-1603. doi: 10.1080/03007995.2018.1476332. Epub 2018 May 29.
Results publication: PubMed 29862621DeVries JH, Desouza C, Bellary S, Unger J, Hansen OKH, Zacho J, Woo V. Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. Diabetes Obes Metab. 2018 Oct;20(10):2426-2434. doi: 10.1111/dom.13396. Epub 2018 Jul 9.
Results publication: PubMed 29907893Carlsson 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.
Results publication: PubMed 30615985Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jodar E, Mehta R, Woo V, Lingvay I. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019 Oct;45(5):409-418. doi: 10.1016/j.diabet.2018.12.001. Epub 2019 Jan 4.
Derived from this study: PubMed 37178435Pulleyblank R, Larsen NB. Cost-Effectiveness of Semaglutide vs. Empagliflozin, Canagliflozin, and Sitagliptin for Treatment of Patients with Type 2 Diabetes in Denmark: A Decision-Analytic Modelling Study. Pharmacoecon Open. 2023 Jul;7(4):579-591. doi: 10.1007/s41669-023-00416-z. Epub 2023 May 13.
Clinical Trials at Novo NordiskLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Global Clinical Registry (GCR, 1452) study director

Novo Nordisk A/S

141 sites in 18 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing semaglutide and sitagliptin in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 141 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 141 sites in India, Russia, Japan, Turkey (Türkiye), Bulgaria and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in HbA1c (Glycosylated Haemoglobin) From Baseline (time frame: Week 0, week 56). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01930188, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2019.