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

Abstract

This systematic review aimed to compare the e cacy 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 were 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% con dence interval, 0.02%, 0.017%]) 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 insigni cant 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.

Knowledge, Attitude, and Practice of Metformin Extended-Release Tablets Among Clinicians in China: A Cross-Sectional Survey

“…However, in our survey, nearly 40% of the clinicians overlooked this advantage. Over 80% prescribed metformin XR because of this effectiveness, which was not backed by the latest evidence (Schwartz et al, 2006;Gao et al, 2008;Donnelly et al, 2009;Aggarwal et al, 2018;Ji et al, 2018;Abrilla et al, 2021;Tan et al, 2021). Our results suggest that a misconception of the features of metformin XR is common among Chinese clinicians, which may lead to inappropriate prescription and fluctuation of long-term glucose control (Li et al, 2020b).…”

“…have demonstrated that the XR formulation improves drug adherence by 10% (Gao et al, 2008) because of its simpler usage (Schwartz et al, 2006;Aggarwal et al, 2018;Ji et al, 2018;Abrilla et al, 2021;Tan et al, 2021). However, in our survey, nearly 40% of the clinicians overlooked this advantage.…”

“…Over the past two decades, metformin has expanded its role with an array of preparations, notably extended-release (XR), a formulation developed as an alternative to conventional immediate-release (IR) tablets, is intended to be used as part of a once-daily dosing regimen (Fujita and Inagaki, 2017). The metformin XR delivers comparable glycemic control efficacy to IR (Schwartz et al, 2006;Gao et al, 2008;Donnelly et al, 2009;Aggarwal et al, 2018;Ji et al, 2018;Abrilla et al, 2021;Tan et al, 2021) and improves compliance due to the reduced dosing (Schwartz et al, 2006;Aggarwal et al, 2018).…”

Metformin use is associated with a reduced risk of acute appendicitis in Taiwanese patients with type 2 diabetes mellitus

“…Because appendicoliths may potentially lead to acute appendicitis 1 , 28 , the promotion of intestinal motility resulting from these adverse effects of metformin may reduce the risk of acute appendicitis because of the reduced occurrence of appendix obstruction by appendicoliths. Because prolonged/slow-release metformin may only have minimal improvement of gastrointestinal intolerance than conventional/immediate-release formulations 29 , it is not surprising that the use of either formulation was associated with a similarly lower risk of acute appendicitis (Table 3 , Models XIII and XIV) taking the increased gut motility as a potential mechanism.…”

Extended versus immediate-release metformin

“…A systematic review of trials of extended-release and immediate-release metformin found that both formulations had a similar effect on lowering HbA 1C , and the only difference in gastrointestinal adverse effects was a lower incidence of dyspepsia with extended-release metformin 1…”