Kellerer M, Kaltoft MS, Lawson J, et al. 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. (Original study)

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.

Discipline Area Score
Internal Medicine 6 / 7
Endocrine 6 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Comments from MORE raters

Endocrine rater

While the results are positive, I remain a skeptical until the study is reproduced by a group not funded by the pharmaceutical manufacturer. If information holds up, the result may be important. Currently, the pharm support leads to hesitation to accept the results without independent corroboration.

Endocrine rater

This is the 2nd or 3rd RCTs showing that in patients failing basal insulin, a once-weekly GLP-1 is just as effective (or slightly better) than t.i.d. rapid-acting pre-prandial insulin. These results should have a major effect in how we treat basal insulin failures, at least initially. As insulin secretion continues to decrease, pre-prandial insulin will probably become necessary in some patients.
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