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

Abstract

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.

Conflict of interest statement

M.K. receives consulting fees from Abbott, Bayer AG, Boehringer Ingelheim, Eli Lilly, MSD, Novo Nordisk, and Sanofi. Payments or honoraria for lectures, presentations, speakers′ bureaus, manuscript writing, or educational events are received from Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, and Novo Nordisk. M.S.K., J.L., and L.L.N. are employees of Novo Nordisk A/S. M.S.K. is a shareholder in Novo Nordisk A/S. K.S. receives consulting fees and support for attending meetings and/or travel from Eli Lilly and Sanofi. Payments or honoraria for lectures, presentations, speakers′ bureaus, manuscript writing, or educational events are provided from Bayer AG, Bioton, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi, and Servier. O.T. has nothing to disclose. S.J. receives payments or honoraria for lectures from Amgen, AstraZeneca, Bayer AG, Berlin Chemie, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, SCIARC, and VIFOR. S.J. participates on Data Safety Monitoring Boards or Advisory Boards for Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim, Eli Lilly, MSD, and Novo Nordisk. S.J. participates in the German Diabetes Association working groups on (i) diabetes prevention and (ii) diabetes and the heart.

© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Change in A, HbA1c (primary endpoint) and B, body weight (secondary endpoint) from randomization to EOT. Primary and secondary endpoints from randomization to week 52. A, Change in HbA1c. Mean estimates (±SE) are from an ANCOVA where missing data were multiple imputed using data from participants within the same group defined by randomized treatment. The dashed line is the overall average value at randomization. B, Change in body weight. Mean (±SE) estimates are from an ANCOVA where missing data were multiple imputed using data from participants within the same group defined by randomized treatment. The dashed line is the overall average value at randomization. ANCOVA, analysis of covariance; CI, confidence interval; EOT, end of treatment; ETD, estimated treatment difference; SE, standard error.