Risk of any?hypoglycaemia with newer antihyperglycaemic agents in patients with?type 2 diabetes: A systematic review and meta‐analysis

摘要

Objectives For patients with type 2 diabetes, newer antihyperglycaemic agents (AHA ), including the dipeptidyl peptidase IV inhibitors (DPP 4i), glucagon‐like peptide‐1 receptor agonists (GLP 1RA ) and sodium glucose co‐transporter 2 inhibitors (SGLT 2i) offer a lower risk of hypoglycaemia relative to sulfonylurea or insulin. However, it is not clear how AHA compare to placebo on risk of any hypoglycaemia. This study evaluates the risk of any and severe hypoglycaemia with AHA and metformin relative to placebo. Design A systematic review and meta‐analysis was conducted of randomized, placebo‐controlled trials ≥12 weeks in duration. MEDLINE , Embase and the Cochrane Library were searched up to April 16, 2019. Studies allowing use of other diabetes medications were excluded. Mantel‐Haenszel risk ratio with 95% confidence intervals were used to pool estimates based on class of AHA and number of concomitant therapies used. Patients Eligible studies enrolled patients with type 2 diabetes ≥18 years of age. Results 144 studies met our inclusion criteria. Any hypoglycaemia was not increased with AHA when used as monotherapy (DPP 4i (RR 1.12; 95% CI 0.81‐1.56), GLP 1RA (1.77; 0.91‐3.46), SGLT 2i (1.34; 0.83‐2.15)), or as add‐on to metformin (DPP 4i (0.95; 0.67‐1.35), GLP 1RA (1.24; 0.80‐1.91), SGLT 2i (1.29; 0.91‐1.83)) or as triple therapy (1.13; 0.67‐1.91). However, metformin monotherapy (1.73; 1.02‐2.94) and dual therapy initiation (3.56; 1.79‐7.10) was associated with an increased risk of any hypoglycaemia. Severe hypoglycaemia was rare not increased for any comparisons. Conclusions Metformin and the simultaneous initiation of dual therapy, but not AHA used alone or as single add‐on combination therapy, was associated with an increased risk of any hypoglycaemia relative to placebo.