Study explores higher doses of semaglutide for people living with type 2 diabetes and obesity

A new phase 2 trial has shown that higher doses of semaglutide — up to 16 mg weekly — may deliver greater weight loss benefits in people with living with type 2 diabetes and overweight or obesity, though with increased side effects.

Published in Diabetes Care, the randomised, placebo-controlled trial was led by Dr Vanita R. Aroda of Brigham and Women's Hospital and included 245 participants with type 2 diabetes and a BMI of 27 kg/m² or more. All participants were already taking metformin and were randomised to receive weekly doses of semaglutide (2 mg, 8 mg, or 16 mg) or placebo over 40 weeks.

The study aimed to assess whether increasing doses of semaglutide could offer greater benefits for blood glucose and weight management. The 16 mg dose did not significantly outperform the 2 mg dose in reducing HbA1c (a difference of -0.3 percentage points; P = 0.245), but it led to significantly greater weight loss (an additional 3.4 kg; P = 0.011).

Using a different statistical approach known as the "hypothetical estimand," the 16 mg dose showed a statistically significant reduction in both HbA1c (-0.5 percentage points; P = 0.015) and body weight (-4.5 kg; P = 0.004) compared with the 2 mg dose.

However, the higher doses were associated with a greater number of gastrointestinal side effects, including nausea and vomiting, leading to more treatment discontinuations. Importantly, no episodes of severe hypoglycemia were reported during the trial.

The findings suggest that while higher doses of semaglutide may offer additional weight loss benefits, the trade-off in tolerability must be carefully considered. Further research is already underway to evaluate the use of high-dose semaglutide in people living with obesity who do not have diabetes.