Semaglutide 2.4 mg Reduces 10-year Risk of Type 2 Diabetes in Patients with Overweight, Obesity

In patients with overweight or obesity, once-weekly semaglutide 2.4 mg reduced the 10-year risk of developing type 2 diabetes (T2D) by approximately 60%, according to new findings presented at the 82nd Scientific Sessions of the American Diabetes Association held June 3-7, 2022, in New Orleans, LA.

The risk reduction was consistent regardless of initial glycemic status, according to the study abstract, and sustained treatment required to maintain the benefit, according to the authors.

W Timothy Garvey, MD

Semaglutide, a sodium-glucose contransporter-2 (SGLT-2) inhibitor, combined with diet and exercise, was assessed for chronic weight management against placebo in the phase 3 STEP clinical trial program which was the foundation for the US Food and Drug Administration approval awarded for that purpose in June 2021.

The current analysis, led by W Timothy Garvey, MD, Butterworth professor of medicine in the department of nutrition science at the University of Alabama School of Medicine, is based on data from 2 phase 3 STEP program trials: the STEP-1 trial, which ran for 68 weeks and demonstrated reductions in body weight with semaglutide 2.4 mg that were 12.7 kg greater than those seen with placebo; and the STEP-4 trial, a discontinuation study, which included a 20-week run in period when patients received semaglutide 2.4 mg followed by randomization to either continue the study drug or switch to placebo for a 48-week withdrawal period. Continued treatment vs switching was associated with further weight reduction.

The post hoc calcuation of 10-year risk of developing T2D was performed using Cardiometabolic Disease Staging (CMDS), a validated Bayesian logistic regression of T2D risk factors, including age, sex, race BMI, triglycerides, HDL, blood pressure and fasting plasma glucose.

When they analyzed the data, Garvey and colleagues found a decrease in risk scores at 68 weeks in both groups: from 18% to 7% with semaglutide and from 18% to 16% with placebo, a reduction of 61% vs 13% (p<.01). For participants receiving semaglutide 2.4 mg, the majority of reduction in risk score occurred during the first 20 weeks, dropping from 21% to 11%, they observed. With continued use of semaglutide from weeks 20 to 68, risk scores fell to 8%, the team reported, but increased to 15% after the switch from the study drug to placebo, a reduction of risk of 32% vs an increase of 41% (p<.01).

The investigators further found that baseline risk scores (week 0) were higher among patients with prediabetes than those with normoglycemia, yet treatment effects were comparable between groups at week 68 (p_interaction =.45).

According to the authors, the observed changes in the proxy risk for developing T2D mirrored changes in body weight, ie, a reduction of 17% with semaglutide vs 3% achieved with placebo in the STEP 1 trial and a reduction of ‍11% for weeks 0 to 20 with semaglutide in STEP 4. In STEP 4, continued treatment with semaglutide led to an additional reduction in weight of 9% which turned to a regain of 6% with the switch to placebo for weeks 20 to 68.

“In summary, treatment with semaglutide reduces the 10-year risk of type 2 diabetes by approximately 60% regardless of initial glycemic status, with sustained treatment required to maintain this benefit,” they concluded. “These data suggest semaglutide could help prevent type 2 diabetes in people with obesity.”

Reference: Garvey TW, Holst-Hansen T, Laursen PN, Rinnov AR, Wilkinson LH. Semaglutide 2.4 mg reduces the 10-year T2D risk in people with overweight/obesity. Diabetes 2022;71(Supplement_1):2-LB