A recent study analyzing data from four pivotal clinical trials—LEADER, STEP 2, SUSTAIN 6, and PIONEER 6—evaluated the impact of concomitant metformin use on gastrointestinal adverse events during the initiation and titration of glucagon-like peptide 1 receptor agonists (GLP-1RA).
Klara Klein, MD, PhD, assistant professor of medicine in the UNC Division of Endocrinology led the 16,996-participant study, of which 76% were treated with metformin. Results showed no significant increase in the occurrence or severity of gastrointestinal adverse events among those using metformin during GLP-1RA initiation and titration. Additionally, concomitant metformin use did not contribute to an elevated risk of GLP-1RA discontinuation among participants who experienced gastrointestinal adverse events. Conversely, the analysis indicated that a higher percentage of metformin nonusers experienced gastrointestinal adverse events and subsequently discontinued the study product compared to metformin users.
These findings provide reassurance to both healthcare providers and patients, suggesting incorporating metformin alongside GLP-1RA therapies does not intensify gastrointestinal symptoms or impact the overall tolerability of the treatment. Instead, increased counseling or slowed titration may be necessary in people who do not use metformin.
This multi-trial analysis, published in Diabetes Care, the journal of the American Diabetes Association, underscores the safety and tolerability of combining metformin with GLP-1RA therapies during initiation and provides valuable insights for clinicians as they navigate personalized treatment plans for individuals with type 2 diabetes.