Semaglutide would halve the risk of type 2 diabetes associated with obesity

Stockholm, Sweden __ The GLP-1 agonist semaglutide (Wegovy®) greatly reduces the estimated 10-year risk of type 2 diabetes in obese people according to post hoc analysis of the STEP 1 and STEP 4 studies.

These results, presented at the European Association for the Study of Diabetes (EASD)[1]suggest that semaglutide, which has been hailed as a “game changer” for the treatment of obesity after receiving marketing approval in 2021,

“Could help prevent type 2 diabetes in overweight or obese people,” the said dr W. Timothy GarveyProfessor and Director of the Diabetes Research Center at the University of Alabama at Birmingham, during his presentation.

Invited to comment on this data that dr Rodolfo J Galindo (Endocrinologist at Emory University in Atlanta, USA) said: “We try very hard to treat people with diabetes, but very little to prevent diabetes. We hope new scientific evidence will show the benefits of weight loss as suggested by Dr. Garvey were illustrated [et ses collègues] to prevent diabetes, will impact the obesity-related chronic disease pandemic.”

The finding of an association between treatment with semaglutide and a reduced risk of developing type 2 diabetes is significant as it shows that it does not only affect body mass index (BMI) for the treatment of overweight people , but that it also represents a way of potentially reducing the complications of obesity such as the occurrence of diabetes, explains Timothy Garvey, who recalls that recent recommendations on the treatment of obesity emphasize interventions aimed at preventing complications.

“Our analysis shows that treatment with semaglutide prevents diabetes through multiple mechanisms. It’s not just a drop in blood sugar. »
Dr Garvey

Combined analysis of data from STEP 1 and STEP

The one from Dr. Garvey et al. experimental data used STEP 1, which compared semaglutide 2.4 mg subcutaneously once weekly to placebo for weight loss in over 1500 predominantly obese (approximately 6% were overweight) subjects. It found that after 68 weeks, semaglutide reduced the estimated risk of developing type 2 diabetes over the next 10 years from 18% at baseline to 7%, compared with 16% for people who received the placebo.

A second similar analysis, the essay STEP 4 treated approximately 800 predominantly obese subjects with 2.4 mg of semaglutide for 20 weeks and then randomly assigned them to receive placebo or continue treatment with semaglutide.

It shows that treatment with semaglutide reduced the estimated 10-year risk of developing type 2 diabetes from 20% at baseline to about 11% at 20 weeks. The risk skyrocketed in study participants who were then switched from semaglutide to placebo. In contrast, the 10-year risk decreased further to 8% in those randomized to receive semaglutide for a total of 68 weeks.

In both studies, Drs. Garvey and his collaborators used the Cardiometabolic Disease Staging (CMDS) tool they previously developed to estimate the 10-year risk of developing type 2 diabetes based on three unmodifiable factors (age, sex, and age). calculate race) and five modifiable factors (BMI, blood pressure, blood sugar, high-density lipoprotein (HDL) cholesterol and triglycerides).

“I don’t know of a better tool to predict the onset of diabetes,” he commented Professor Michael A Nauck (Diabetes Department, St. Josef Hospital in Bochum, Germany).

The new analyzes also showed that in the STEP 1 study, the effect of semaglutide on reducing the risk of developing type 2 diabetes was approximately the same regardless of whether participants with prediabetes were enrolled in the study or are normoglycemic.

The main effects of blood sugar changes

Of the five modifiable components of the CMDS tool, the drop in blood glucose caused by semaglutide was the parameter that contributed most to the change in estimated risk of diabetes, just under half the estimated change, the report says, according to Dr. Garvey. The other four modifiable components each had roughly similar effects on the estimated risk, with the change in BMI accounting for approximately 15% of the observed effect.

“Our analysis shows that treatment with semaglutide prevents diabetes through multiple mechanisms. It’s not just a drop in blood sugar,” noted Dr. Garvey sure.

Limits the scope of these results

Professor Nauck says it’s not surprising that semaglutide prevents diabetes when one of its effects is to reduce hyperglycemia, an indicator of diabetes onset.

In fact, semaglutide was first approved to treat type 2 diabetes (known as Ozempic®, Novo Nordisk) at doses slightly lower than those approved for obesity. It’s also available as an oral drug to treat diabetes (Rybelsus).

Professor Nauck also noted that at least one previously reported study (SCALE) had previously shown the association between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg daily dose, known as Saxenda®) and a subsequently reduced incidence of type 2 diabetes, but using actual clinical data Results over 3 years of follow-up rather than a calculated extrapolation of the likelihood of diabetes.

The SCALE Obesity and Prediabetes study randomized 2,254 people with prediabetes and overweight or obese to weekly treatment with liraglutide 3.0 mg or placebo. After 160 weeks of treatment, the cumulative incidence of type 2 diabetes was 2% in subjects receiving liraglutide and 6% in subjects receiving placebo, with a significant reduction in the hazard ratio of 79% for the incidence of on-treatment diabetes with liraglutide.

The STEP 1 and STEP 4 studies were sponsored by Novo Nordisk, the company that markets Semaglutide (Wegovy). dr Garvey said he has served as an unpaid consultant to Novo Nordisk, as well as Boehringer Ingelheim, Eli Lilly, Jazz and Pfizer. He is also principal investigator for multi-center clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee and Pfizer. dr Galindo said he has been an advisor or advisor to Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi and Weight Watchers and has received research funding from Dexcom, Eli Lilly and Novo Nordisk. Nauck stated that he is an advisor or advisor to Novo Nordisk, as well as Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor and ShouTi/Gasherbrum, receives research funding from MSD, is a member of a data monitoring committee and security for Inventiva, and spokesperson for Novo Nordisk as well as Eli Lilly, Menarini/Berlin Chemie, MSD and Sun Pharmaceuticals.

This article originally appeared on Medscape.com as a game changer Semaglutide halves the risk of diabetes from obesity. Translated and adapted by Aude Lecrubier.

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