Phase 3 · Semaglutide

SUSTAIN trial results

Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin in Subjects With Type 2 Diabetes. A 30-week Randomised, Double-blind, Double-dummy, Active-controlled, Parallel-group, Multi-centre and Multi-national Trial

Participants
868
Status
completed
Completed
2019-04-15
Sponsor
Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT03061214), updated at source Mar 2, 2021. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What SUSTAIN measured first

Change in HbA1cPercentage of glycosylated haemoglobin · Week 0, week 30 · mean
MeasureSemaglutide 0.5 mgn=288Semaglutide 1.0 mgn=290Sitagliptinn=290
On-treatment without rescue medication obs. period-1.5(1.1)-1.8(0.9)-1.0(0.9)
In-trial observation period-1.5(1.1)-1.7(1.0)-0.9(0.9)
Side effects by arm

Side effects in SUSTAIN

Percent of participants affected, From the date of first dose of trial product (week 0) to end of treatment (week 30) + post treatment follow-up of 5 weeks.. The most common events the registry lists.

EventSemaglutide 0.5 mgSemaglutide 1.0 mgSitagliptin
Any serious event6.3%6.6%4.1%
Diarrhoea20.2%16.9%6.9%
Upper respiratory tract infection9.8%13.1%14.8%
Nausea7.7%13.4%1.7%
Decreased appetite7.3%7.9%1.4%
Lipase increased7.7%4.5%7.6%
Vomiting4.9%6.6%1%
Diabetic retinopathy6.3%4.8%3.4%
Nasopharyngitis5.9%3.1%3.8%
Abdominal discomfort2.8%5.2%0.3%
Secondary outcomes

What else it measured

Change in Body WeightKilogram (kg) · Week 0, week 30 · mean
Semaglutide 0.5 mgn=238Semaglutide 1.0 mgn=239Sitagliptinn=253
-3.0(3.8)-4.2(3.7)-0.4(2.5)
Change in Fasting Plasma Glucose (FPG)Millimoles per liter (mmol/L) · Week 0, week 30 · mean
Semaglutide 0.5 mgn=237Semaglutide 1.0 mgn=238Sitagliptinn=253
-2.18(2.5)-2.62(2.13)-1.0(1.74)
Change in Self-measured Plasma Glucose (SMPG) - Mean 7-point ProfileMillimoles per liter (mmol/L) · Week 0, week 30 · mean
Semaglutide 0.5 mgn=236Semaglutide 1.0 mgn=238Sitagliptinn=251
-2.5(2.4)-3.3(2.2)-1.6(2.0)
Change in Self-measured Plasma Glucose (SMPG) - Mean Postprandial Increment Over All MealsMillimoles per liter (mmol/L) · Week 0, week 30 · mean
Semaglutide 0.5 mgn=234Semaglutide 1.0 mgn=237Sitagliptinn=251
-1.0(2.2)-1.2(2.1)-0.7(2.2)
Change in Fasting Insulin - Ratio to BaselineRatio of fasting insulin · Week 0, week 30 · geometric mean
Semaglutide 0.5 mgn=229Semaglutide 1.0 mgn=237Sitagliptinn=254
1.06(46.6)1.03(51.2)1.01(41.6)
Change in Fasting C-peptide - Ratio to BaselineRatio of fasting C-peptide · Week 0, week 30 · geometric mean
Semaglutide 0.5 mgn=234Semaglutide 1.0 mgn=239Sitagliptinn=254
1.08(30.3)1.05(32.4)1.0(32.2)
Change in Fasting Glucagon - Ratio to BaselineRatio of fasting glucagon · Week 0, week 30 · geometric mean
Semaglutide 0.5 mgn=205Semaglutide 1.0 mgn=206Sitagliptinn=221
0.89(32.4)0.89(28.1)0.93(25.0)
Change in Fasting Proinsulin - Ratio to BaselineRatio of fasting proinsulin · Week 0, week 30 · geometric mean
Semaglutide 0.5 mgn=234Semaglutide 1.0 mgn=241Sitagliptinn=253
0.68(62.7)0.59(65.3)0.81(58.2)
Change in Fasting Proinsulin/Insulin Ratio - Ratio to BaselineRatio of fasting proinsulin/insulin · Week 0, week 30 · geometric mean
Semaglutide 0.5 mgn=226Semaglutide 1.0 mgn=237Sitagliptinn=253
0.63(50.2)0.57(52.1)0.80(45.4)
Change in Fasting HOMA-B (Beta-cell Function) - Ratio to BaselineRatio of fasting HOMA-B · Week 0, week 30 · geometric mean
Semaglutide 0.5 mgn=228Semaglutide 1.0 mgn=236Sitagliptinn=252
1.81(57.3)1.95(59.1)1.25(46.1)
Change in Fasting HOMA-IR (Insulin Resistence) - Ratio to BaselineRatio of fasting HOMA-IR · Week 0, week 30 · geometric mean
Semaglutide 0.5 mgn=228Semaglutide 1.0 mgn=236Sitagliptinn=252
0.81(60.9)0.74(63.2)0.90(52.0)
Change in Patient Reported Outcome Questionnaire: SF-36v2™ ScoreScore on a scale · Week 0, week 30 · mean
MeasureSemaglutide 0.5 mgn=246Semaglutide 1.0 mgn=249Sitagliptinn=257
Physical component summary (PCS)1.3(5.9)1.1(6.0)0.0(5.8)
Physical functioning0.6(5.6)0.9(7.4)-0.3(5.5)
Role-physical1.4(7.6)0.2(6.9)-0.0(7.0)
Bodily pain0.6(8.4)0.4(9.9)0.0(9.8)
General health3.3(8.8)2.9(9.4)2.2(9.0)
Mental component summary (MCS)1.2(8.0)0.5(8.4)1.5(7.7)
Social functioning1.3(7.0)-0.4(7.8)0.8(7.6)
Role-emotional1.3(8.5)0.9(8.9)1.0(8.6)
Vitality1.2(9.8)1.4(10.1)1.1(9.1)
Mental health0.9(8.7)0.4(9.1)1.1(7.9)
The trial

How SUSTAIN was run

This trial is conducted in Africa, Asia, Europe and South America. The aim of the trial is to compare the effect of once-weekly dosing of two dose levels of semaglutide versus sitagliptin 100 mg once-daily on glycaemic control after 30 weeks of treatment. Subjects will remain on their stable pre-trial metformin.

  • Semaglutide 0.5 mg OW + sitagliptin placebo OD
  • Semaglutide 1 mg OW + sitagliptin placebo OD
  • Sitagliptin OD + semaglutide placebo 0.5 mg OW
  • Sitagliptin OD + semaglutide placebo 1 mg OW
Who could join the trial

Inclusion Criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Male or female, age equal to or above 18 years at the time of signing informed consent - Subjects diagnosed with type 2 diabetes and on stable treatment in a period of 60 days prior to screening with metformin equal to or above 1500 mg (or maximum tolerated dose equal to or above 1000 mg). Stable is defined as unchanged medication and unchanged daily dose - HbA1c 7.0 - 10.5 % (53-91 mmol/mol) (both inclusive) Exclusion Criteria: - Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential not using an adequate contraceptive method throughout the trial including the 5 week follow-up period (adequate contraceptive measure as required by local regulation or practice) - Any disorder 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 60 days before screening. An exception is short-term treatment (equal to or below 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value equal to or above 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 m\^2 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

Published papers

Papers from SUSTAIN

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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