Safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with type 2 diabetes mellitus fasting during Ramadan: a systematic review and meta-analysis

BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM) during Ramadan fasting is limited. No meta-analysis has summarized the safety and effectiveness of GLP-1RAs in these situations. AIM To evaluate the safety and efficacy of GLP-1RA in patients with T2DM fasting during Ramadan. METHODS Electronic databases were systematically searched for relevant studies that featured GLP-1RA in the intervention arm and other glucose-lowering medications in the control arm. The primary outcome was adverse events (AEs) during Ramadan for both groups; other outcomes included changes in glycemic and anthropometric measures during the peri-Ramadan period. RESULTS Four studies [three randomized-controlled trials with low risk of bias (RoB) and one prospective observational study with serious RoB] involving 754 subjects were analyzed. GLP-1RA group achieved greater glycated hemoglobin reduction than the non-GLP-1RA group [mean difference (MD): -0.31%, 95%CI: -0.61 to -0.01, P = 0.04, I 2 = 77%] with a lower risk of documented symptomatic hypoglycemia (risk ratio = 0.38, 95%CI: 0.16 to 0.88, P = 0.02). Any AEs, serious AEs, or AEs that led to treatment discontinuation were comparable between the two groups. The GLP-1RA group experienced greater weight loss compared to the non-GLP-1RA group (MD: -2.0 kg, 95%CI: -3.37 to -0.63, P = 0.004, I 2 = 95%). There were comparable changes in blood pressure and lipid profile between the two groups. GLP-1RA users experienced higher risks of gastrointestinal AEs, nausea, and vomiting; however, the risks of heartburn, abdominal pain, and diarrhea were similar in both groups. CONCLUSION Limited evidence suggests that GLP-1RAs are safe for T2DM management during Ramadan, offering modest benefits in blood sugar control and weight loss. Large multicenter trials are needed to confirm their safety and efficacy in at-risk populations, improving clinical practice decision-making.