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Striking the Balance of GLP-1 and Glucagon Agonism to Minimise Potential Risks Based on outcomes from safety and pharmacokinetic studies with GLP-1 analogues, the most common side effect observed with GLP-1 agonism is dose-dependent nausea and vomiting ( Even with careful engineering of receptor balance, potency and pharmacokinetics, problems may still crop up, as illustrated by SAR425899s unexpected development failure due to excessive gastrointestinal adverse events during its Phase 2 trials
Across the three treatment groups (dulaglutide 1.5 mg, dulaglutide 0.75 mg, and placebo), there were no cases of diabetic ketoacidosis or amputations, and hypotensive episodes/syncope occurred in 0%, 1% and 1%, genital infections in 0%, 0% and 1%, fractures in 1%, 1% and 1%, and gastrointestinal events in 32%, 21% and 17% of patients, respectively [31]
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