2187-PUB: Identifying Risk Predictors for Gastrointestinal Adverse Events with Once-Weekly Semaglutide

Gastrointestinal adverse events (GI AEs) are common with glucagon-like peptide-1 receptor agonists (GLP-1RAs). We aimed to identify risk predictors for GI AEs with once-weekly semaglutide to support clinicians identify high-risk patients. Data from SUSTAIN 1-10 and two SUSTAIN Japanese trials were used to assess the effects of age, region, ethnicity, diabetes duration, gender, renal function, smoking status, HbA1c, body weight (BW), alanine aminotransferase and bilirubin on the incidence of GI AEs with semaglutide vs. non-GLP-1RA comparators (exenatide extended release, dulaglutide and liraglutide were excluded). Changes in HbA1c and BW were assessed by GI AE status. Frailty (age, renal impairment, smoking) and female gender were associated with marginally higher risk of GI AEs than non-frailty and male gender, regardless of treatment. With semaglutide, patients with lower baseline BW were at higher risk of GI AEs vs. those with higher BW. With comparators, lower baseline BW was associated with lower risk than higher BW. These results were confirmed by formal statistical analysis (data not shown). Semaglutide reduced HbA1c and BW across the trials, regardless of GI AEs (Figure). In conclusion, GI AEs are hard to predict although they tend to be more common in frail vs. non-frail patients and females vs. males, regardless of treatment. Semaglutide reduced HbA1c and BW regardless of the presence/absence of GI AEs. Disclosure T. Vilsboll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp \u0026 Dohme Corp., Sanofi. S. Harring: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. I. Holst: Employee; Self; Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp \u0026 Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp \u0026 Dohme Corp., Norgine B.V., Novo Nordisk A/S. K. Kvist: Employee; Self; Novo Nordisk A/S. I. Lingvay: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk A/S, Sanofi, TARGET PharmaSolutions, Valeritas, Inc. Other Relationship; Self; Novo Nordisk A/S. Funding Novo Nordisk A/S