Higher Dose of Semaglutide Enhances Weight Loss Effects Safely

Results from two late-stage clinical trials show that tripling the standard dose of semaglutide can significantly increase weight loss in individuals with obesity, both with or without a type 2 diabetes diagnosis. Published back to back in The Lancet Diabetes & Endocrinology, results from both trials show that a higher dose of this drug could help those who have not been able to achieve sufficient weight loss with other existing treatments.  

Semaglutide is a weight loss drug that targets the glucagon-like peptide-1 (GLP-1), sold by Novo Nordisk under the brand name Wegovy to treat people with obesity and under Ozempic to treat patients with both type 2 diabetes and obesity. “Once-weekly subcutaneous semaglutide 2.4 mg is approved for weight management in people with obesity and related complications; however, some individuals do not reach their therapeutic goals with this dose,” stated the researchers. 

The two Phase IIIb clinical trials tested the effects of a 7.2 mg dose of semaglutide and compared it to the currently approved dose of 2.4 mg, as well as to a placebo. In the STEP UP trial, over 1,400 participants with obesity and no diabetes were treated over the course of 72 weeks. In the STEP UP T2D trial, more than 500 patients with obesity and type 2 diabetes were treated during the same period of time. All participants received diet and exercise recommendations regardless of which treatment they were given. 

In the STEP UP trial, the higher semaglutide dose led to an average weight loss of 18.7% in participants without type 2 diabetes, compared to 16% for those treated with the standard dose and four percent with placebo. Almost a third of people treated with the higher dose had a bodyweight reduction of more than 25%, and 83.4% of patients with prediabetes at the start of the trial had returned to normal blood sugar levels by the end of the trial, compared to 73.8% for the standard dose and 36.6% for the placebo group. 

“These results support a favorable benefit–risk profile of semaglutide 7.2 mg for weight management in people with obesity,” wrote the authors. “The greater magnitudes of bodyweight reduction seen in this trial, as well as the improvements in cardiovascular risk factors and glucose control, can have beneficial effects on health goals in clinical practice.”

In the STEP UP T2D trial, a higher semaglutide dose resulted in an average bodyweight reduction of 13.2%, compared to 10.4% for the standard dose and 3.9% for the placebo. While the overall weight loss was lower in this patient population, the researchers highlighted the importance of these results given the fact that type 2 diabetes and its treatment makes weight loss more difficult. Achieving a bodyweight loss of about 10% is a major target for many people with type 2 diabetes, helping improve metabolic symptoms and potentially having disease modifying effects. 

Across both trials, adverse events such as nausea, diarrhea, and vomiting were more common among the group who received the higher dose, with most of the patients seeing these symptoms resolved before the end of the trial. In patients with type 2 diabetes, hypoglycemia risk was low with the higher dose and comparable to that of the lower dose and the placebo treatments. 

“The landscape for weight management is continuously changing,” concluded the researchers. “For people with obesity who are inadequately treated, the greater magnitude of bodyweight change with semaglutide 7.2 mg, compared with lower doses, could help with managing obesity-related complications, which had not been addressed with previous treatments.”