SAFETY OF GLP-1 RECEPTOR AGONISTS IN PATIENTS WITH TYPE 1 DIABETES MELLITUS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Author(s)
BHOLANATH CHOWDHURY, MPH1, Manik Chhabra, Post Doc2, Anoop Kumar, PhD1, Ritika tak, MPH1, Monika Sharma, MPH1, Kamre Aalam, PharmD3.
1Pharmacology, Delhi Pharmaceutical Sciences and Research University, New Delhi, India, 2Department of Epidemiology and Biostatistics, Western University, London, ON, Canada, 3Pharmacy practice, ISF College of Pharmacy, Moga, India.
1Pharmacology, Delhi Pharmaceutical Sciences and Research University, New Delhi, India, 2Department of Epidemiology and Biostatistics, Western University, London, ON, Canada, 3Pharmacy practice, ISF College of Pharmacy, Moga, India.
OBJECTIVES: To evaluate the safety profile of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as adjunctive therapy in patients with type 1 diabetes mellitus (T1DM).
METHODS: MEDLINE, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) assessing the safety of GLP-1 RAs in patients with T1DM. Two independent reviewers performed screening, data extraction, and quality assessment independently. Risk of bias was evaluated using the Cochrane Risk of Bias tool. Safety outcomes were pooled using the metabin package in R, using the mental-hazal method (check spelling).
RESULTS: Of 57,850 identified citations, 26 unique RCTs were included with 3660 patients, median age range 13-75 years, 52% females and 48% males. Studies predominantly evaluated liraglutide over 4-52 weeks. Compared with controls, GLP-1 RAs were associated with significantly increased risks of any adverse events (RR 1.11; 95% CI 1.08-1.14; I2=53.4%; 17 trials), withdrawal due to adverse events (RR 3.16; 95% CI 1.81-5.51; I2=55.0%; 12 trials), and gastrointestinal adverse events (RR 1.89; 95% CI 1.60-2.24; I2=50.0%; 6 trials). Elevated risks were observed for nausea (RR 2.98; 95% CI 2.42-3.66; 19 trials), vomiting (RR 1.45; 95% CI 1.10-1.91; 14 trials), decreased appetite (RR 4.50; 95% CI 3.18-6.35; 11 trials), gastroesophageal reflux disease (RR 5.95; 95% CI 1.37-25.87; 3 trials), and dyspepsia (RR 3.76; 95% CI 1.37-10.31; 4 trials). Subgroup analyses demonstrated that liraglutide containing regimens were the primary contributors to increased gastrointestinal adverse events, particularly nausea (RR 2.76; 95% CI 2.24-3.41; 11 trials), decreased appetite (RR 4.32; 95% CI 2.87-6.48; 7 trials), and dyspepsia (RR 3.99; 95% CI 1.36-11.70; 3 trials).
CONCLUSIONS: GLP-1 RAs used as adjunctive therapy in T1DM were associated with a significantly increased risk for gastrointestinal adverse events and treatment discontinuation. Clinicians should carefully monitor gastrointestinal tolerability in patients with T1DM, considering GLP-1 receptor agonists.
METHODS: MEDLINE, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) assessing the safety of GLP-1 RAs in patients with T1DM. Two independent reviewers performed screening, data extraction, and quality assessment independently. Risk of bias was evaluated using the Cochrane Risk of Bias tool. Safety outcomes were pooled using the metabin package in R, using the mental-hazal method (check spelling).
RESULTS: Of 57,850 identified citations, 26 unique RCTs were included with 3660 patients, median age range 13-75 years, 52% females and 48% males. Studies predominantly evaluated liraglutide over 4-52 weeks. Compared with controls, GLP-1 RAs were associated with significantly increased risks of any adverse events (RR 1.11; 95% CI 1.08-1.14; I2=53.4%; 17 trials), withdrawal due to adverse events (RR 3.16; 95% CI 1.81-5.51; I2=55.0%; 12 trials), and gastrointestinal adverse events (RR 1.89; 95% CI 1.60-2.24; I2=50.0%; 6 trials). Elevated risks were observed for nausea (RR 2.98; 95% CI 2.42-3.66; 19 trials), vomiting (RR 1.45; 95% CI 1.10-1.91; 14 trials), decreased appetite (RR 4.50; 95% CI 3.18-6.35; 11 trials), gastroesophageal reflux disease (RR 5.95; 95% CI 1.37-25.87; 3 trials), and dyspepsia (RR 3.76; 95% CI 1.37-10.31; 4 trials). Subgroup analyses demonstrated that liraglutide containing regimens were the primary contributors to increased gastrointestinal adverse events, particularly nausea (RR 2.76; 95% CI 2.24-3.41; 11 trials), decreased appetite (RR 4.32; 95% CI 2.87-6.48; 7 trials), and dyspepsia (RR 3.99; 95% CI 1.36-11.70; 3 trials).
CONCLUSIONS: GLP-1 RAs used as adjunctive therapy in T1DM were associated with a significantly increased risk for gastrointestinal adverse events and treatment discontinuation. Clinicians should carefully monitor gastrointestinal tolerability in patients with T1DM, considering GLP-1 receptor agonists.
Conference/Value in Health Info
2026-09, ISPOR Asia Pacific 2026, Bangkok, Thailand
Value in Health, Volume 55, Issue S1
Code
CO2
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity)