Metformin significantly lowers death risk due to cardiac and
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The Italian Society of Diabetology and the Italian Association of Clinical Diabetologists are developing new guidelines for drug treatment of type 2 diabetes. The effects of anti-hyperglycaemic drugs on all-cause mortality and major adverse cardiovascular events (MACEs) were included among the critical clinical outcomes. Researchers therefore carried out an updated meta-analysis on the effects of metformin on these outcomes.

A MEDLINE and EMBASE search was performed to identify all randomized controlled trials (RCTs) with duration greater than 52 weeks, in which metformin was compared with either placebo/no therapy or active comparators. MACEs (restricted for RCT reporting MACEs within their study endpoints) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified endpoints) were considered as the primary endpoints. Mantel-Haenszel odds ratio (MH-OR) with 95% confidence interval was calculated for all endpoints considered.

Key Findings:
-- Metformin was associated with a nonsignificant reduction of all-cause mortality.

-- However, this association became statistically significant after excluding RCTs comparing metformin with sulfonylureas, SGLT-2 inhibitors or GLP-1 analogues.

-- Metformin was associated with a lower risk of MACEs compared with comparator treatments.

-- Similar results were obtained in a post-hoc analysis including all RCTs fulfilling criteria for inclusion in the analysis.

Conclusively, this updated meta-analysis suggests that metfomin is significantly associated with lower risk of MACEs and tendentially lower all-cause mortality compared to placebo or other anti-hyperglycaemic drugs.