Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial

Diabetes Obes Metab. 2022 Sep;24(9):1788-1799. doi: 10.1111/dom.14765. Epub 2022 Jun 29.


Aim: To compare the efficacy and safety of once-weekly (OW) semaglutide versus thrice-daily (TID) insulin aspart (IAsp) in participants with inadequately controlled type 2 diabetes (T2D) treated with insulin glargine (IGlar) and metformin.

Materials and methods: SUSTAIN 11 (NCT03689374) was a randomized (1:1), parallel, open-label, multinational, phase 3b trial. After a 12-week run-in to optimize once-daily IGlar U100, 1748 adults with T2D (HbA1c >7.5% to ≤10.0%) were randomized to OW semaglutide or TID IAsp as add-on to optimized IGlar and metformin for 52 weeks. The primary outcome was change in HbA1c from randomization to week 52. Confirmatory secondary endpoints included the occurrence of severe hypoglycaemic episodes and change in body weight (BW). Safety was assessed.

Results: HbA1c (randomization: 8.6% [70.0 mmol/mol]) decreased by 1.5% points (16.6 mmol/mol) and 1.2% points (13.4 mmol/mol) with semaglutide (n = 874) and IAsp (n = 874), respectively (estimated treatment difference [ETD] -0.29% points [95% confidence interval {CI} -0.38; -0.20]; P < .0001 for non-inferiority). Few severe hypoglycaemic episodes were recorded in either group, with no statistically significant difference between the groups. Change in BW from randomization (87.9 kg) to week 52 was in favour of semaglutide (-4.1 kg) versus IAsp (+2.8 kg) (ETD -6.99 kg [95% CI -7.41; -6.57]). A higher proportion of participants experienced adverse events with semaglutide (58.5%) versus IAsp (52.1%); most were mild to moderate.

Conclusions: In this basal insulin-treated population, OW semaglutide improved glycaemic control to a greater extent than TID IAsp and provided numerically greater weight loss.

Keywords: GLP-1 analogue; glycaemic control; hypoglycaemia; insulin therapy; type 2 diabetes; weight control.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose
  • Body Weight
  • Diabetes Mellitus, Type 2* / chemically induced
  • Diabetes Mellitus, Type 2* / drug therapy
  • Drug Therapy, Combination
  • Glucagon-Like Peptides
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemia* / chemically induced
  • Hypoglycemia* / prevention & control
  • Hypoglycemic Agents / adverse effects
  • Insulin Aspart / therapeutic use
  • Insulin Glargine / adverse effects
  • Metformin* / therapeutic use
  • Treatment Outcome


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin Glargine
  • semaglutide
  • Glucagon-Like Peptides
  • Metformin
  • Insulin Aspart

Associated data

  • ClinicalTrials.gov/NCT03689374