Risks of metformin sustained release versus metformin immediate release on gastrointestinal side effects in patients with type 2 diabetes: a Meta-analysis

Objective To compare the risks of gastrointestinal side effects in patients with type 2 diabetes mellitus (T2DM) by Meta-analysis between metformin extended-release (MXR) and metformin immediate-release (MIR) treatment. Methods Databases of PubMed, the Cochrane Library, Web of Science, SinoMed, Wanfang and CNKI were searched for randomized controlled trials (RCTs) with therapy of MXR and MIR in T2DM patients from establishment of the database to March 2018. Stata 12.0 and RevMan 5.3 were used to analyze the risk of gastrointestinal adverse reactions. Results Thirteen RCTs with a total of 3 039 patients were recruited. Compared with MIR treatment, MXR treatment significantly reduced the risks of nausea/vomiting, dyspepsia and flatulence (RR=0.61, 95%CI: 0.43-0.85, Z=2.87, P=0.004; RR=0.47, 95%CI: 0.30-0.74, Z=3.32, P=0.0009; RR=0.35, 95%CI: 0.17-0.69, Z=3.02, P=0.002) . The risks of diarrhea events were associated with the age of the patients: subgroup analysis showed that MXR treatment significantly reduced the risk of diarrhea in patients under 50 years of age (RR=0.21, 95%CI: 0.08-0.54, Z=3.25, P=0.001) instead of those patients over 50 years old (RR=0.99, 95%CI: 0.76-1.29, Z=0.08, P=0.940) ; Meta-regression showed that age was the main source of heterogeneity in diarrhea-studying group, while gender, body mass index, duration of diabetes, and drug dosage didn′t significantly affect the incidence of diarrhea events. Conclusions Compared with MIR treatment, MXR treatment could effectively lower the risks of nausea/vomiting, dyspepsia and flatulence in T2DM patients. MXR can be used as an alternative therapy for T2DM patients under 50 yrs who are unable to tolerate MIR treatment due to gastrointestinal side effects. Key words: Diabetes mellitus, type 2; Metformin; Gastrointestinal side effects; Sustained-release metformin