Publications of the Week: New options for weight control

Background: The rising prevalence of obesity and its contribution to multiple comorbidities present a significant health-care system phenomenon. Medications allowing for body weight reduction, with glucagon-like peptide-1 (GLP-1) receptor agonists among them, are increasingly used. Those medications modifying the hormonal milieu of the gastrointestinal tract have been so far used as injections. The availability of oral equivalents could be of value to individuals and health-care systems.

Methods: This randomized controlled trial included adults without diabetes, with a body mass index (BMI) of ≥30 kg/m² (or 27 kg/m² with body weight–related comorbidities). Patients were using either semaglutide 50 mg/d or matching placebo. The main outcomes were related to the percentage of weight loss achieved during 68 weeks of the study.

Results: The study included 667 patients at a mean age of ~50 years and with a mean BMI of ~37 kg/m². Patients treated with semaglutide lost 15.1% of body weight over the course of the study in comparison to the loss of 2.4% among patients on placebo. A body weight loss of 5%, 10%, 15%, and 20% occurred in 85%, 69%, 54%, and 34% of actively treated patients, respectively. The corresponding figures among patients on placebo were 26%, 12%, 6%, and 3%. Gastrointestinal adverse effects were more common among patients treated with semaglutide (nausea, 52% vs 15%; constipation, 28% vs 15%; vomiting, 24% vs 4%). Benign neoplasms were observed more commonly among patients on semaglutide (~7.5% vs 4%).

Conclusions: The authors concluded that oral semaglutide at a daily dose of 50 mg results in a substantial degree of weight loss, likely similar to that achieved with an injectable form.

McMaster editors’ commentary: The epidemics of obesity and its associated complications represent a major challenge for both individuals and health-care systems. The armamentarium of drugs with efficacy approaching that previously reserved for bariatric surgery is rapidly expanding, and oral semaglutide is one of such options. Cost and manufacturing capacity currently remain the main barriers for those new classes of medications potentially affecting multiple gastrointestinal hormones. The common short-term and medium-term gastrointestinal adverse effects of GLP-1 receptor agonists have been well recognized by now. However, the effects of long-term use of some medications, possibly life-long, remain not entirely clear—here the authors point to an unexpected increase in benign neoplasms, suggesting future studies should pay attention to such events.