Study finds Semaglutide's effects on long-term weight loss in individuals with obesity

Two studies presented at the European Congress on Obesity investigated the long-term effects of semaglutide on weight loss and explored the relationship between cardiovascular benefits and initial weight or extent of weight loss.

Semaglutide, a GLP-1 medication typically prescribed for adults with type 2 diabetes, is also approved for weight management in individuals with obesity or overweight who have at least one comorbidity. This medication class mimics the actions of the body's natural incretin hormones, aiding in post-meal blood sugar regulation. By modulating these hormone levels, semaglutide can induce a feeling of fullness, thereby reducing daily calorie consumption.

In the SELECT trial spanning from October 2018 to June 2023, 17,604 adults aged 45 or older from 41 countries were given semaglutide (2.4mg) or placebo for an average of 40 months. They were overweight or obese but no diabetes and a history of cardiovascular events.

The findings are as follows:

1. Semaglutide users saw a 20% lower risk of heart attack, stroke, or cardiovascular death and lost an average of 9.4% body weight.

2. In the semaglutide group, weight loss persisted up to week 65 and was maintained for four years, with participants achieving an average body weight reduction of 10.2% and a waistline decrease of 7.7cm, compared to 1.5% and 1.3cm respectively in the placebo group.

3. The semaglutide group experienced a significant 6.9% reduction in average waist circumference-to-height ratio, compared to 1% in the placebo group. After two years, over half (52%) of semaglutide-treated participants shifted to a lower BMI category, compared to 16% of those receiving placebo.

4. Semaglutide treatment provided cardiovascular benefits regardless of initial weight or the extent of weight loss. This implies that even individuals with mild obesity or modest weight loss may experience improved cardiovascular outcomes with semaglutide therapy.

“Our findings show that the magnitude of this treatment effect with semaglutide is independent of the amount of weight lost, suggesting that the drug has other actions which lower cardiovascular risk beyond reducing unhealthy body fat. These alternative mechanisms may include positive impacts on blood sugar, blood pressure, or inflammation, as well as direct effects on the heart muscle and blood vessels, or a combination of one or more of these,” said Professor John Deanfield from University College London, UK.

Reference: Ryan, D.H., Lingvay, I., Deanfield, J. et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med (2024). https://doi.org/10.1038/s41591-024-02996-7