Semaglutide Significantly Reduces Long-Term Diabetes Risk Among Obesity Patients

Rapid Reviews in Cardiology®Rapid Reviews in Cardiology® - June 2022

New post hoc data from the STEP 1 and 4 trials show an approximate 60% risk reduction of type 2 diabetes over 10 years versus placebo.

Semaglutide Significantly Reduces Long-Term Diabetes Risk Among Obesity Patients

W. Timothy Garvey, MD

Once-weekly 2.4 mg semaglutide is associated with an approximate 60% reduced risk of type 2 diabetes in patients with obesity, according to new findings presented at the American Diabetes Association (ADA) 2022 Scientific Sessions this weekend.

In new late-breaking data presented by study author W. Timothy Garvey, MD, endocrinologist and Butterworth Professor of Medicine in the department of nutrition science at University of Alabama School of Medicine, a team of US investigators found the GLP-1 agonist provided a substantially decreased risk of type 2 diabetes development among people with obesity, regardless of their baseline glycemic status, when combined with diet and exercise.

The approval comes months after the US Food and Drug Administration (FDA) streamlined approval of Novo Nordisk’s 2.0 mg subcutaneous injection semaglutide (Ozempic) as a once-weekly treatment for adults with type 2 diabetes. The agent was previously indicated for reducing major adverse cardiovascular event (MACE) risk in adults with both diabetes and cardiovascular disease.

Garvey, who disclosed previous work with Novo Nordisk, and colleagues sought to assess type 2 diabetes development risk associated with the once-weekly 2.4 mg dose in people with obesity using data from the pivotal STEP 1 and STEP 4 trials for semaglutide.

STEP 1 was a global, multicenter, double-blind, randomized, placebo-controlled trial assessing semaglutide (n = 1306) versus placebo (n = 655) for weight loss in patients with overweight or obesity and without type 2 diabetes at baseline, over 68 weeks. STEP 4 was a 20-week run-in trial of semgalutide among the same treatment population, with a 48-week randomized withdrawal assessment afterward.

Investigators calculated a post hoc 10-year type 2 diabetes risk among STEP 1 and 4 participants to receive semaglutide using a Bayesian logistic regression of type 2 diabetes risk factors called Cardiometabolic Disease Staging (CMDS), which stages cardiometabolic risk at 5 levels from metabolically healthy (stage 0) to present type 2 diabetes and cardiovascular disease (stage 4). Patients in STEP 1 across either treatment arm were stratified by baseline status of normoglycemia or prediabetes.

Among STEP 1 patients with normoglycemia, patients receiving semaglutide decreased their geometric mean risk score for type 2 diabetes from 15.5% at baseline to 6.3% by week 68, versus a decrease from 15.9% to 14.2% among patients receiving placebo. Among patients with prediabetes, the semaglutide arm decreased mean diabetes risk from 22.4% at baseline to 8.3% at week 68, while the placebo arm decreased only from 21.5% to 18.3%.

Overall, patients treated with semaglutide in STEP 1 decreased mean type 2 diabetes risk scores from 18.2% to 7.1% (61% risk reduction), versus the placebo arm’s decrease from 17.8% to 15.6% (13% risk reduction; P <.01).

In STEP 4, patients receiving semaglutide reported a baseline type 2 diabetes risk score of 20.6%. Among treated patients, mean risk decreased to 11.4% at week 20, then 7.7% at week 68 following the withdrawal period. Among patients to receive placebo, mean risk decreased to 10.7% at week 20, but then increased up to 15.4% after the withdrawal period—indicating a 32% overall reduction with semaglutide versus a 41% increase with placebo (P <.01).

Investigators observed that type 2 diabetes risk score changes mirrored that of weight loss from the original STEP 1 and 4 trial outcomes.

“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.”

The 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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