Visual Abstract
GLP-1 receptor agonists are associated with gastrointestinal adverse events (GI AEs). This post-hoc analysis of AWARD-11 in patients with inadequately controlled T2D on metformin evaluated GI AEs with once weekly dulaglutide (DU) 1.5 mg (N=612), 3 mg (N=616) and 4.5 mg (N=614) through 52 weeks. Patients were started on once weekly DU 0.75 mg for 4 weeks followed by stepwise dose escalation every 4 weeks to their final randomized dose (Fig A and B). Safety analyses included all patients with at least 1 dose of DU. Nausea (15.9%), diarrhea (10.4%), and vomiting (8.5%) were most frequent AEs with <2% of patients discontinuing treatment due to 1 of these events. Treatment discontinuation from nausea was 1.3% DU 1.5 mg, 3 mg and 1.5% 4.5 mg; from diarrhea was 0.2% DU 1.5 mg, 1.0% 3 mg, 4.5 mg; from vomiting was 0% DU 1.5 mg, 0.8% 3 mg and 1.3% 4.5 mg. Nausea incidence for all groups peaked after initial DU 0.75 mg dose and fell to <2% by week 4 (Fig A). Most GI AEs were mild to moderate in severity and lasted <7 days. Nausea prevalence (new or ongoing events; events with no end date assumed as ongoing) peaked around treatment initiation and eventually fell to <5% (Fig B). Nausea frequency was highest across all groups early after initiation and fell during each subsequent study interval, even after escalating to 3 mg or 4.5 mg. This should allow for more patients to achieve treatment goals with acceptable GI tolerability.
J. Van: None. J. P. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. E. Bonora: Advisory Panel; Self; Abbott, Bayer AG, BD, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Lilly Diabetes, MSD Corporation, Sanofi, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. S. Raha: Employee; Self; Eli Lilly and Company. H. Jung: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. D. Cox: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. Konig: Employee; Self; Eli Lilly and Company. J. Peleshok: Employee; Self; Eli Lilly and Company.
