Metformin extended-release versus metformin immediate-release for adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

This systematic review aimed to compare the efficacy and tolerability of metformin extended-release (MXR) and the conventional metformin immediate-release (MIR) in adults with type 2 diabetes mellitus (T2DM). PubMed, the Cochrane Library and ClinicalTrials.gov, from database inception to 15 October 2020, and other sources were searched for randomized controlled trials (RCTs) that compared equal daily doses of MXR and MIR in adults with T2DM. Random-effects model meta-analysis was performed to obtain pooled mean difference (MD) of change from baseline for continuous outcomes (glycemic and serum lipid control and anthropometrics) and risk ratio (RR) for dichotomous outcomes (gastrointestinal and serious adverse events). Statistical analysis involving 9 published RCTs with 2609 subjects revealed that MIR was associated with better HbA1c lowering (MD 0.09% [95% confidence interval, 0.02%, 0.17%]) and serum lipid control except LDL-C lowering, while MXR reduced only the cumulative incidence of dyspepsia (RR 0.58 [0.34, 0.98]). MXR and MIR were similar in all other considered outcomes. The use of MXR over MIR among adults with T2DM was associated with statistically worse but likely clinically insignificant HbA1c lowering, similar plasma glucose lowering, and minimal improvement of metformin intolerance. This information may guide patient-physician discussions in choosing between the two formulations.