Changes in Glucose Metabolism and Glycemic Status with Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants with Prediabetes in the STEP Program

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posted on 2022-06-20, 18:07 authored by Leigh Perreault, Melanie Davies, Juan P. Frias, Peter Nørkjaer Laursen, Ildiko Lingvay, Sriram Machineni, Anette Varbo, John P.H. Wilding, Signe Olrik Rytter Wallenstein, Carel W. le Roux

Objective

This analysis of 3,375 adults with overweight/obesity across the STEP 1, 3, and 4 trials evaluated whether more participants with prediabetes had normoglycemia after 68 weeks’ treatment with once-weekly semaglutide 2.4 mg plus lifestyle intervention versus placebo, and assessed changes in glucose metabolism in participants with prediabetes.

Research Design and Methods

STEP 1, 3, and 4 were phase 3, 68-week, randomized, placebo-controlled, multinational trials; STEP 4 had a 20-week semaglutide run-in and 48-week randomized period. Analyses included changes (week 0–68; before the washout period) in glycemic status (prespecified: STEP 1 and 3; post-hoc: STEP 4), and in HbA1c, fasting plasma glucose (FPG), and insulin resistance (HOMA-IR) among participants with prediabetes (post-hoc).

Results

Significantly more participants with baseline (week 0) prediabetes (n=1,536) had normoglycemia at week 68 with semaglutide versus placebo (STEP 1, 84.1% vs. 47.8%; STEP 3, 89.5% vs. 55.0%; STEP 4, 89.8% vs. 70.4%; all P < 0.0001). Fewer participants with baseline normoglycemia had prediabetes at week 68 with semaglutide versus placebo (STEP 1, 2.9% vs. 10.9%; STEP 3, 3.2% vs. 5.8%; STEP 4, 1.1% vs. 5.0%). Semaglutide resulted in greater improvements in HbA1c, FPG, and HOMA-IR than placebo among participants with baseline prediabetes (all P < 0.01).

Conclusions

STEP 1, 3, and 4 collectively provide a robust assessment of the effects of semaglutide on glucose metabolism and prediabetes in a large cohort of adults with overweight/obesity while on treatment. Among participants with baseline prediabetes, 68 weeks’ treatment with semaglutide vs. placebo led to significant improvements in glucose metabolism and a higher likelihood of normoglycemia.