Semaglutide confers significant weight loss in obese, nondiabetic patients
Individuals with obesity but without diabetes experienced significant weight reduction with daily doses of the glucagon-like peptide-1 receptor agonist semaglutide, according to a recent study presented at ENDO 2018.
In this multinational, double-blind, dose-ranging study, 957 adults with obesity (mean age 47 years, 35 percent male, mean BMI 39 kg/m2) without diabetes and with one or more previous nonsurgical attempts at weight loss were randomized to receive once-daily subcutaneous doses of semaglutide (0.05, 0.1, 0.2, 0.3, or 0.4 mg with a starting dose of 0.05 mg which was escalated every 4 weeks to reach target dose) or liraglutide (3 mg with a starting dose of 0.6 mg which was escalated weekly to reach target dose) or placebo. All participants received monthly counselling sessions on diet and physical activity.
Over the 1-year period, patients on liraglutide had an estimated mean weight loss of 7.8 percent of their body weight.
At 1 year, patients on semaglutide (0.05 mg) experienced a significant reduction in weight loss compared with those on placebo (mean, -6.0 percent vs -2.3 percent; p=0.001). [ENDO 2018, abstract OR12-5]
The percentage reduction in weight increased with increasing doses of semaglutide with -8.6, -11.6, -11.2, and -13.8 percent estimated mean weight loss with 0.1, 0.2, 0.3, and 0.4 mg semaglutide, respectively (p<0.0001 vs placebo [0.1–0.4 mg]). Estimated weight loss was also significantly greater among patients on semaglutide 0.2–0.4 mg compared with those on liraglutide (p<0.01).
Weight loss of ≥10 percent occurred in more patients on semaglutide 0.1 mg (37 percent), 0.2 mg (56 percent), 0.3 mg (58 percent), and 0.4 mg (65 percent) compared with placebo (10 percent; p<0.0001 vs placebo 0.1–0.4 mg), while 34 percent of patients on liraglutide experienced ≥10 percent weight loss.
“This randomized study of weight loss induced with semaglutide in people with obesity but without diabetes has shown the highest weight reductions yet seen for any pharmaceutical intervention,” said study lead author Professor Patrick M. O’Neil, Director of the Weight Management Center at the Medical University of South Carolina in Charleston, South Carolina, US.
“[I]n combination with dietary and physical activity counselling, all semaglutide doses from 0.05 to 0.4 mg daily were tolerated and resulted in dose-related reductions in body weight that were superior to placebo among people with obesity without diabetes,” he said.
According to O’Neil, no new safety concerns emerged, with mild-to-moderate nausea the most commonly occurring adverse event in patients on semaglutide.
The use of diabetes drugs in patients who are obese but not diabetic is not an uncommon practice, said Dr Vivien Lim, a specialist in endocrinology at Gleneagles Hospital, Singapore. Liraglutide, for example, is approved in Singapore for the treatment of obesity, she said.
“What it does is enhances the feeling of satiety and reduces appetite. This ultimately leads to an overall reduced caloric intake which will then lead to weight loss if it exceeds caloric expenditure which it usually would. I feel that it allows my patients to understand what the feeling of fullness is and to eat to satiety. This leads to a lifestyle change in terms of smaller portion sizes and if this was cultivated indefinitely, it would stand the patient in good stead in terms of overall weight loss and sustainability,” said Lim.