Responder analysis of subjects achieving HbA1c >= 1% and weight loss >= 5% across SUSTAIN 1-5 clinical trials

Semaglutide, a GLP-1 analog in development for once-weekly subcutaneous treatment of T2D, demonstrated superior HbA1c and body weight reductions vs comparators across the SUSTAIN 1–5 clinical trials. We report a post-hoc analysis of these trials evaluating the proportion of subjects who achieved a composite endpoint of both ≥1% HbA1c reduction and ≥5% weight loss. SUSTAIN 1–5 evaluated the efficacy and safety of once-weekly semaglutide (0.5 mg and 1.0 mg) vs comparators (placebo, sitagliptin, insulin glargine, exenatide extended-release, or placebo+basal insulin) in subjects with T2D. The proportion of subjects achieving both ≥1% HbA1c reduction and ≥5% weight loss was greater with semaglutide 0.5 mg (25–35%) and 1.0 mg (38–56%) vs comparators (2–13%; all comparisons, p<0.0001). The proportion of subjects achieving this combined endpoint was also greater with semaglutide 1.0 mg vs 0.5 mg (p<0.0001, SUSTAIN 2, 4 and 5; p=0.17, SUSTAIN 1), suggesting a dose-dependent effect. In all five trials, severe or BG-confirmed symptomatic hypoglycemia events were fewer or similar with semaglutide vs comparators. Semaglutide was well tolerated, with a safety profile similar to that of other GLP-1 receptor agonists. With semaglutide, significantly more subjects achieved the clinically meaningful composite endpoint of ≥1% HbA1c reduction and ≥5% weight loss.