Higher-Dose Semaglutide Delivers Meaningful Weight Loss In Patients With Obesity And Diabetes

A once-weekly 2.4 mg injection of the GLP-1-receptor agonist semaglutide, with lifestyle changes, led to meaningful weight loss and improvements in cardiometabolic risk factors in overweight or obese adults with type 2 diabetes in the STEP 2 trial.

Semaglutide given by subcutaneous injection at a dose of 0.5 mg to 1 mg weekly is approved in the United States for treatment of type-2 diabetes. Semaglutide is currently being investigated as an anti-obesity agent, given studies showing it helps with weight loss.

In the phase-3 STEP 2 trial, 1,210 overweight or obese adults (BMI >=27 kg/m2) with type-2 diabetes were randomly allocated to once-weekly injections of semaglutide (2.4 mg or 1.0 mg) or placebo, plus a lifestyle intervention.

​

At 68 weeks, mean bodyweight had dropped by 9.6% in the high-dose group versus 7.0% in the normal-dose group and 3.4% in the placebo group (P<0.0001), Dr. Ildiko Lingvay of the University of Texas Southwestern Medical Center, in Dallas, and colleagues report in The Lancet.

Clinically meaningful reductions in bodyweight of at least 5% were reported in 69% of patients on semaglutide 2.4 mg versus 57% of patients on the lower dose and 29% of patients on placebo, they report.

The weight loss was accompanied by a hemoglobin A1c reduction of 1.6% with semaglutide 2.4 mg, 1.5% with semaglutide 1.0 mg, and 0.4% with placebo.

Patients treated with semaglutide 2.4 mg had greater improvements in cardiometabolic risk factors and physical functioning compared with patients treated with placebo. The safety profile of semaglutide 2.4 mg was typical of a GLP-1 receptor agonist, the researchers report.

The most common adverse events were transient, mild to moderate gastrointestinal (GI) symptoms and more patients discontinued semaglutide than placebo. The rate of GI adverse events was slightly higher with semaglutide 2.4 mg than 1.0 mg, but discontinuations due adverse events were low overall, and were similar in both semaglutide groups, they note.

"Semaglutide 2.4 mg is a promising treatment option for weight management in patients with overweight or obesity and type 2 diabetes," Dr. Lingvay and colleagues conclude.

The STEP 2 trial results are in line with results of the STEP 1 trial, published last month in The New England Journal of Medicine.

Semaglutide 2.4 mg once-weekly "is the most effective drug intervention we have seen for weight management," senior author of that paper Dr. Robert Kushner told Reuters Health at the time.

Roughly 70% of participants in STEP 1 "reached a weight loss of at least 10% of their baseline weight, a threshold that is meaningful for the improvement of multiple obesity-related health concerns, such as diabetes, high blood pressure, gastroesophageal reflux disease (GERD), and pain from arthritis of the knees," Dr. Kushner said in an email.

The authors of a Lancet Comment published with the STEP 2 results note that the "road to ideal pharmacological weight management is full of barriers. Now GLP-1 analogues offer a new opportunity for effective weight control - and the first of these, liraglutide, has already been approved by regulatory agencies such as the US Food and Drug Administration and the European Medicines Agency for the treatment of obesity and overweight."

"Although the effectiveness profile of semaglutide is being fully defined, it appears that semaglutide offers the advantage of being given once a week rather than daily, with possibly higher efficacy on weight loss than liraglutide," write Dr. Roberto Latini and Dr. Lidia Staszewsky of Mario Negri Institute of Pharmacological Research in Milan, Italy.

The STEP 2 trial was funded by Novo Nordisk, which makes semaglutide. Several authors of the STEP 2 trial have disclosed financial relationships with the company. The authors of the accompanying comment declared no competing interests.

—Reuters Staff

Source