Dulaglutide

Mechanism (as reported)

A review of GLP-1 receptor agonists reports that agents in this class share mechanisms including augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion at hyper- or euglycemia, deceleration of gastric emptying preventing large post-meal glycemic increments, and reduction in calorie intake and body weight. (PMID: 33068776)

Key findings (each cites a source)

• A randomized, open-label, phase 3b trial (SUSTAIN 7) in adults with inadequately controlled type 2 diabetes compared semaglutide versus dulaglutide once weekly and reported reductions in HbA1c and bodyweight with both dulaglutide doses at week 40. [PMID 29397376]
• The SUSTAIN 7 trial reported gastrointestinal disorders as the most frequently reported adverse events across both semaglutide and dulaglutide groups, and that gastrointestinal disorders were also the most common reason for discontinuing treatment. [PMID 29397376]
• A state-of-the-art review reports that GLP-1 receptor agonists share class mechanisms including augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion at hyper- or euglycemia, deceleration of gastric emptying, and reduction in calorie intake and body weight. [PMID 33068776]
• The review states that once-weekly injectable GLP-1 receptor agonists for type 2 diabetes include dulaglutide (among others). [PMID 33068776]
• A double-blind, placebo-controlled 26-week trial in youths with type 2 diabetes reported that once-weekly dulaglutide (0.75 mg or 1.5 mg) decreased glycated hemoglobin from baseline at 26 weeks versus placebo, and a higher proportion of participants in pooled dulaglutide groups achieved glycated hemoglobin <7.0% compared with placebo. [PMID 35658022]
• In the youth trial, fasting glucose increased in the placebo group and decreased in pooled dulaglutide groups, and there were no between-group differences in change in BMI; gastrointestinal adverse events were reported as higher with dulaglutide than with placebo. [PMID 35658022]
• A predefined secondary analysis of a double-blind, randomized, placebo-controlled trial evaluated dulaglutide in the context of smoking cessation and reported that participants receiving dulaglutide drank 29% less alcohol (relative effect 0.71, 95% CI 0.52-0.97, P=0.04) at week 12 compared with placebo. [PMID 37991022]
• In SURPASS-CVOT design and baseline characteristics, dulaglutide is used as the active comparator in a randomized, double-blind cardiovascular outcomes trial in participants with type 2 diabetes and atherosclerotic cardiovascular disease, with the primary outcome defined as time to first major adverse cardiovascular event (CV death, myocardial infarction, or stroke). [PMID 37758044]
• In a cardiovascular outcomes report (SURPASS-CVOT), the primary composite endpoint (death from cardiovascular causes, myocardial infarction, or stroke) occurred in 12.2% in the tirzepatide group versus 13.1% in the dulaglutide group, and the incidence of adverse events appeared similar between groups with more gastrointestinal adverse events observed in the tirzepatide group. [PMID 41406444]