Long-Acting Metformin Vs. Metformin Immediate Release in Patients With Type 2 Diabetes: A Systematic Review

Abstract

Background: Metformin, a commonly used antidiabetic medication, is available in both an immediate-release (IR) formulation and a long-acting formulation (metformin extended-release; XR).Objective: We performed a systematic review to compare the effectiveness, safety, and patient compliance and satisfaction between the metformin IR and XR formulations.Method: We searched for randomized control trials (RCTs) and observational studies comparing the effectiveness, safety, or patient compliance and satisfaction of metformin XR with metformin IR using the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Following report screening, data collection, and risk of bias assessment, we separately pooled data from RCTs and observational studies using the Grading of Recommendation Assessment, Development, and Evaluation approach to rate the quality of evidence.Result: We included five RCTs, comprising a total of 1,662 patients, and one observational study, comprising 10,909 patients. In the meta-analyses, no differences were identified in outcomes of effectiveness and safety between the two forms of metformin (including change in HbA1c: mean difference (MD), 0.04%, 95% confidence interval [CI], −0.05–0.13%, fasting blood glucose: MD, −0.03 mmol/L, 95% CI, −0.22–0.15 mmol/L, postprandial blood glucose: MD, 0.50 mmol/L, 95% CI, −0.71–1.72 mmol/L, adverse events of abdominal pain: relative risk (RR), 1.15, 95% CI, 0.57–2.33, all-cause death (RR, 3.02, 95% CI 0.12–73.85), any adverse events (RR, 1.14, 95% CI 0.97–1.34), any adverse events leading to treatment discontinuation: RR, 1.51, 95% CI, 0.82–2.8, any gastrointestinal adverse events: RR, 1.09, 95% CI, 0.93–1.29, diarrhea: RR, 0.82, 95% CI, 0.53–1.27, flatulence: RR, 0.43, 95% CI, 0.15–1.23, nausea: RR, 0.97, 95% CI, 0.64–1.47, severe adverse events: RR, 0.64, 95% CI, 0.28–1.42, and vomiting: RR, 1.46, 95% CI, 0.6–3.56). Data from both the RCTs and the observational study indicate mildly superior patient compliance with metformin XR use compared with metformin IR use; this result was attributable to the preference for once-daily administration with metformin XR.Conclusion: Our systematic review indicates that metformin XR and IR formulations have similar effectiveness and safety, but that metformin XR is associated with improved compliance to treatment.

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

“…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.…”

“…Good adherence to metformin improves clinical outcomes ( Nathan et al, 2006 ; Patel et al, 2019 ; Wu et al, 2018 ; Walker et al, 2020 ). Randomized controlled trials and systematic reviews 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.…”

“…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 ).…”

“…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 in Patients With COVID-19: A Systematic Review and Meta-Analysis

“…Vitamin B12 deficiency is a potential long-term risk in metformin users, but its clinical relevance has not yet been proven ( 54 , 55 ). People may choose once-daily long-acting metformin instead of metformin immediate release if they are hesitating in taking drug more than once per day ( 56 ). Reducing over 1/3 death with benefits for other health events found in the current study, the tradeoff of metformin for people with COVID-19 is clear.…”