SUN-646 - Comparative Efficacy and Tolerability of Extended-Release Versus Immediate-Release Metformin in Type 2 Diabetes: A Systematic Review and Meta-Analysis

Background:
Diabetes mellitus is a chronic metabolic disorder characterized by sustained hyperglycemia resulting from impaired insulin secretion, insulin action, or both. Metformin remains the first-line pharmacological therapy for Type 2 Diabetes Mellitus (T2DM). The immediate-release formulation (MIR) is widely prescribed, while the extended-release formulation (MXR) was developed to improve gastrointestinal tolerability, dosing convenience, and treatment adherence. This meta-analysis compares the efficacy, glycemic outcomes, and safety profiles of MXR versus MIR in adults with T2DM.

Methods:
A systematic search of PubMed, ClinicalTrials.gov, the Cochrane Library, and Embase was conducted for randomized controlled trials published up to December 2025 comparing MXR and MIR in adults with T2DM. Ten trials encompassing 2,944 participants (MXR: 1,566; MIR: 1,378) were included. Primary outcomes were changes in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial glucose (PPG). Secondary outcomes included gastrointestinal adverse events, lipid parameters (HDL and LDL cholesterol), and anthropometric measures. Data were analyzed using Review Manager (RevMan).

Results:
MXR and MIR demonstrated comparable efficacy in reducing HbA1c (MD = 0.057; 95% CI −0.039 to 0.152) and FBG (MD = 0.030; 95% CI −0.131 to 0.191). MIR was more effective in lowering PPG levels. MXR was associated with a significantly lower risk of dyspepsia (MD = 0.58; 95% CI 0.35 to 0.98). No significant differences were observed for diarrhea, nausea and vomiting, or abdominal discomfort. MIR showed a modestly greater increase in HDL cholesterol, while LDL levels were generally comparable, with subgroup analysis indicating a potential advantage for MXR at a 1500 mg dose. Weight changes did not differ significantly between groups.

Conclusion:
MXR and MIR provide equivalent control of HbA1c and fasting glucose, with MIR demonstrating superior postprandial glucose reduction. However, MXR offers improved gastrointestinal tolerability, particularly regarding dyspepsia, which may enhance long-term adherence. Future large-scale studies are warranted to further validate these findings and explore dose-specific benefits.

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