In the Semaglutide Treatment Effect in People with obesity (STEP) 1, 3, and 4 trials, participants with baseline prediabetes had improved glucose metabolism and a higher likelihood of normoglycemia after 68 weeks’ treatment with weekly semaglutide 2.4 mg plus lifestyle intervention.
The 68-week phase 3 trials compared semaglutide with placebo in 3,375 adults with overweight/obesity. Primary outcomes differed slightly among the studies but generally included changes in glycemic status, HbA1c, fasting plasma glucose (FPG), and HOMA insulin resistance (HOMA-IR). The results showed significantly more participants had normoglycemia at week 68 with semaglutide than placebo (STEP 1, 84.1% vs. 47.8%; STEP 3, 89.5% vs. 55.0%; STEP 4, 89.8% vs. 70.4%). “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%),” the researchers report. “Semaglutide resulted in greater improvements in HbA1c, FPG, and HOMA-IR than placebo among participants with baseline prediabetes (all P < 0.01).”
Editorial: Describing these findings as setting prevention of type 2 diabetes (T2D) as a “new bar for pharmacologic weight loss,” an editorialist writes: “The analyses support the concept of a pharmacologic weight loss strategy for preventing T2D, even in the setting of rigorous therapeutic lifestyle changes. As such, there is a critical need for studies that are specifically designed to assess this outcome.… Since it is understood that normoglycemia and weight loss are not sustained following cessation of therapy, it would be important to assess much longer-term maintenance strategies, such as the benefits of ongoing or intermittent therapy, once initial treatment goals are achieved. Future studies should also include assessment of personalized medicine approaches to identify patients who are more likely to benefit from a given intervention, as well as the long-term impact on comorbidities and/or complications.”
