Semaglutide 2.4 mg Reduces Long-Term Type 2 Diabetes Risk


W. Timothy Garvey discusses the results of a study leveraging data from STEP 1 and STEP 4 to determine the reduction in 10-year risk of type 2 diabetes seen with use of semaglutide 2.4 mg vs placebo therapy.

Use of semaglutide 2.4 mg could reduce the 10-year risk of progression to type 2 diabetes by 60%, according to new data presented at the American Diabetes Association (ADA) 82nd Scientific Sessions.

Presented by W. Timothy Garvey, MD, professor of medicine and director of the Diabetes Clinic Research Center at University of Alabama at Birmingham, the study used Cardiometabolic Disease Staging (CMDS) to assess the 10-year type 2 diabetes risk and determined use of semaglutide 2.4 mg was associated with an approximately 60% reduction in risk of type 2 diabetes regardless of initial glycemic status, with sustained treatment required to maintain this benefit.

Having received approval for the treatment of obesity in June 2021, semaglutide 2.4 mg ushered in a new era of weight loss therapies with the FDA’s recognition of the benefit shown in the STEP trials, which compared semaglutide 2.4 mg against placebo and other doses of semaglutide in patients with overweight or obesity, regardless of diabetes status. In the ADA 2022 analysis, Garvey and colleagues sought to determine the effects of semaglutide 2.4 mg on long-term risk of type 2 diabetes seen in the STEP 1 and STEP 4 trials.

In STEP 1, patients underwent treatment with semaglutide versus placebo for 68 weeks. Results of the trial suggest the change in body weight from baseline to week 68 was 12.7 kg greater than reductions in body weight seen with placebo therapy. In STEP 4, investigators assessed the effects of semaglutide 2.4 mg discontinuation. Results of the trial indicated maintaining treatment with semaglutide 2.4 compared with switching to placebo therapy was associated with continued weight loss over the next 48 weeks.

For the ADA 2022 analysis, Garvey and colleagues used data from these studies and CMDS, a validated Bayesian logistic regression of type 2 diabetes risk factors, to calculate the 10-year risk of type 2 diabetes. Upon analysis, investigators observed the majority of the risk score reduction observed with semaglutide 2.4 mg occurred between weeks 0 and 20, with risk dropping from 21% to 11% during this time period. Further analysis suggested risk scores decreased further to 8% with continued semaglutide 2.4 mg use during weeks 20-68 but increased to 15% following the switch to placebo therapy.

Results of the analysis suggest week 0 risk scores were higher in patients with prediabetes compared to their normoglycemic counterparts, but the effects of treatment were comparable at week 68. Investigators pointed out the apparent changes in risk score correlated to changes in body weight, which was 17% with semaglutide and 3% with placebo in STEP 1 and 11% for weeks 0-20 with semaglutide in STEP 4. An additional 9% reduction in body weight was observed with continued semaglutide 2.4 mg compared to a 6% regain when switching to placebo for weeks 20-68.

For more on this study and other data surrounding semaglutide 2.4 mg at ADA 2022, Endocrinology Network caught up with Garvey at the meeting and that conversation can be found in the video below.

This study, “Semaglutide 2.4 mg Reduces the 10-Year T2D Risk in People with Overweight/Obesity,” was presented at ADA 2022.

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