Semaglutide 2.4 mg given weekly with diet and exercise reduced the 10-year risk of type 2 diabetes in obese patients compared to placebo
Semaglutide 2.4 mg given as a weekly subcutaneous injection to patients with obesity but without type 2 diabetes in combination with diet and exercise, led to a significant reduction in their 10-year risk of developing type 2 diabetes compared to placebo according to the findings of a study by US researchers presented at the 58th European Association for the Study of Diabetes (EASD) 2022.
Obesity is a major public health challenge and several lines of evidence from both observational and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterised by atherogenic dyslipidaemia, hyper-insulinaemia/glucose intolerance, hypertension, atherosclerosis and adverse cardiac remodelling and heart failure. Although diet and exercise are recommended as a first step to reduce obesity, some evidence shows that among obese individuals who have lost weight, multiple compensatory mechanisms encouraging weight gain, can persist for at least 12 months after weight loss. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is approved as an adjunct to diet and exercise in adults with insufficiently controlled type 2 diabetes mellitus. However, the STEP 1 trial showed that semaglutide at a dose of 2.4 mg weekly in combination with a lifestyle intervention could also result in sustained, clinically relevant reductions in body weight among patients with a body mass index (BMI) > 30. Moreover, in a further trial (STEP 4), researchers examined the effect of continuing vs withdrawing treatment with semaglutide on weight loss maintenance and showed that after a 20-week run-in period, maintaining treatment with semaglutide 2.4 mg once weekly, compared with switching to placebo resulted in continued weight loss over the following 48 weeks.
With clear evidence that semaglutide could lead to weight loss, whether this also reduced an individual’s risk of developing type 2 diabetes was unclear and was the objective of the study presented at the EASD meeting. Researchers used data from both STEP 1 and 4, to assess an individual’s 10-year risk of developing type 2 diabetes. The team used the cardiometabolic disease staging tool which uses three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, high-density lipoprotein (HDL) cholesterol, and triglycerides) to predict an individual’s percentage risk of developing the disease over the next 10 years.
Semaglutide and 10-year diabetes risk
For the STEP 1 trial, the 10-year risk scores of developing T2D after 68 weeks of treatment decreased from 18.2% to 7.1% with semaglutide 2.4 mg, and 17.8% to 15.6% with placebo (p < 0.01). In STEP 4, most of the risk score reduction with semaglutide 2.4 mg occurred during weeks 0-20, from 20.6% to 11.4% but the risk score decreased further to 7.7% with continued semaglutide 2.4 mg during weeks 20-68 but increased to 15.4% after a switch to placebo (p < 0.01). In addition, data from STEP 4 showed that weight loss was 11% for weeks 0 – 20 and a further 9% with continued semaglutide 2.4 mg vs a 6%
regain with switch to placebo for weeks 20 – 68.
The authors concluded that treatment with semaglutide 2.4 mg reduces the 10-year risk of T2D by
~60% adding that sustained treatment was required to maintain this benefit but suggested that semaglutide 2.4 mg could help prevent type 2 diabetes in people with obesity.