Efficacy of Once-Weekly Semaglutide vs Thrice-Daily Insulin Aspart as Add-On to Metformin and Insulin Glargine in Type 2 Diabetes
abstract
This abstract is available on the publisher's site.
Access this abstract nowAIMS
The SUSTAIN 11 trial (NCT03689374) compared 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 was a randomized (1:1), parallel, open-label, multinational, phase 3b trial. After a 12-week run-in to optimize once-daily IGlar U100, 1,748 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 occurrence of severe hypoglycemic episodes and change in body weight (BW). Safety was assessed.
RESULTS
HbA1c (randomization: 8.6% [70.0 mmol/mol]) decreased by 1.5%-point [16.6 mmol/mol] and 1.2%-point (13.4 mmol/mol) with semaglutide (n=874) and IAsp (n=874), respectively (estimated treatment difference [ETD] -0.29%-point [95% confidence interval [CI] -0.38;-0.20]; p<0.0001 for non-inferiority). Few severe hypoglycemic episodes were recorded in either group, with no statistically significant difference between groups. Change in BW from randomization (87.9 kg) to week 52 was in favor 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 glycemic control to a greater extent than TID IAsp and provided numerically greater weight loss. This article is protected by copyright. All rights reserved.
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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 May 11;[EPub Ahead of Print], M Kellerer, MS Kaltoft, J Lawson, LL Nielsen, K Strojek, Ö Tabak, S JacobFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Type 2 diabetes is a progressive disease, often requiring treatment intensification. For those individuals already on basal insulin, it was common in the past to intensify treatment by adding rapid-acting prandial insulin and adopting a basal-bolus insulin regimen much alike the one used in people with type 1 diabetes. This paper explores whether a simpler approach—adding semaglutide, a once-weekly GLP-1 receptor agonist (GLP1-RA)—is a suitable alternative to escalation to s complex multiple insulin dose. The results show a greater HbA1c reduction with semaglutide (−1.5%-point; P < .0001 for noninferiority) than with adding three prandial injections of insulin aspart (−1.2%-point) at the end of the 52-week treatment. One may argue about the clinical impact of an absolute difference of 0.3%-point HbA1c between the two treatments, but these improvements in glycaemic control need to be interpreted in the light of other important features of the use of semaglutide. Surprisingly enough, there was no difference in the rate of hypoglycaemic events, although it may be argued that the low rate of events in insulin-treated subjects came at the expense of a conservative algorithm for insulin dose adjustment and careful treatment monitoring by the investigators as per the nature of the trial. On the contrary, a 7-kg difference occurred at the end of the trial between the two treatments, with semaglutide being associated with an average body weight reduction of 4 kg. Semaglutide was associated with more adverse events which also caused greater premature treatment discontinuation (3.7 and 0.7%), due mainly to gastrointestinal side effects. Nonetheless, for all who remained in the trial, all assessments of treatment satisfaction were generally greater with semaglutide. This is not too difficult to account for. It is indeed one insulin injection a day plus one semaglutide injection a week versus four injections a day with the basal bolus regimen; it is merely the fasting plasma glucose monitoring for basal insulin titration in one case versus multiple glucose monitoring throughout the day and careful prandial insulin titration in the other. The improvement in treatment satisfaction is an important element, as it may favour better adherence to treatment and therefore translate into a more sustained glycaemic control. Current guidelines have evolved suggesting GLP1-RAs to be used before starting basal insulin. These, as well as results obtained with other GLP1-RAs1 expand this recommendation, suggesting that adding a GLP1-RA can offer a valid alternative to insulin treatment intensification even in people with advanced type 2 diabetes. Furthermore, these results imply the possibility that complex insulin treatment regimens could be simplified by converting them in a combination of basal insulin and GLP1-RAs.
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