The impact of gastrointestinal adverse events on weight loss with liraglutide 3.0 mg as adjunct to a diet and exercise programme

Background and aims: To explore any associations between gastrointestinal adverse events (GI AEs) and weight loss with liraglutide 3.0 mg/day in addition to a diet and exercise programme in individuals without type 2 diabetes who had obesity (BMI >30 kg/m2) or overweight (BMI 27‐29.9 kg/m2) with at least one comorbidity. Materials and methods: The SCALE Obesity and Prediabetes trial was a randomised, double‐blind, multi‐centre trial in which individuals (mean age 45.1 years, 78.5%female,meanweight 106.2 kg,mean BMI 38.3 kg/m2, 61% with prediabetes) were enrolled in a long‐term weight management programme and randomised to liraglutide 3.0 mg (n=2487) or placebo (n=1244). These data are from an exploratory analysis based on groups of individuals defined by occurrence of GI AEs (0‐16 weeks, 0‐ 56 weeks). Weight loss at week 56 is presented as least squares means using LOCF, with p‐values denoting whether or not GI AEs had a significant effect on treatment. Results: Overall, liraglutide 3.0 mg was associated with a greater weight loss from baseline than placebo (8.0% vs. 2.6%, respectively, p1 episode of nausea/vomiting during 0‐56 weeks, regardless of treatment (liraglutide 3.0 mg: nausea/vomiting, ‐7.8%, no nausea/vomiting, ‐8.1%; placebo: nausea/vomiting ‐2.5%, no nausea/vomiting ‐2.6%, p=0.81). Similar results were seen if all other types of GI AE combined were included.Moreover, no significant differences were observed at week 56 for weight loss in individuals who experienced 0, 1, 2‐3, or >4 GI AEs in the first 16 weeks (7.7‐8.2%with liraglutide 3.0 mg vs. 2.3‐3.0% with placebo, p=0.24), or during the entire 56 weeks of treatment (7.7‐8.4% with liraglutide 3.0 mg vs. 2.4‐3.2% with placebo, p=0.55). Although those experiencing 0 GI AEs appeared to performslightly better than the other groups, thismay be explained by the higher withdrawal rate as the number of GI AE increase. These results were further supported by comparable mean weight loss profiles over time across the 0, 1, 2‐3, or >4 GI AE groups. Conclusion: The weight loss observed with liraglutide 3.0 mg is not explained by the occurrence of GI AEs, including nausea/vomiting.