Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

Aims The aim of the meta-analysis of randomized controlled trials (RCTs) was to compare the effectiveness of glycemic control and hypoglycemia risk of combination therapy (metformin plus a low hypoglycemic risk antidiabetic drug) vs. standard metformin monotherapy, in patients with untreated type 2 diabetes mellitus (T2DM). Methods We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through October 31, 2021 to find relevant RCTs. Efficacy outcomes were changes in hemoglobulin A1c (HbA1c) and fast plasma glucose (FPG) from baseline as well as proportion of patients achieving HbA1c < 7%; the safety outcome was hypoglycemia risk. Results We identified 14 RCTs comprising 5326 patients with untreated T2DM. Mean treatment duration was 28.1 weeks. Pooled results showed that compared to metformin monotherapy, combination therapy was associated with a reduction in HbA1c (mean difference: −0.48 %, −0.58 to − 0.38) and FPG (mean difference: −0.92 mmol/L, −1.14 to − 0.69), and more patients achieving HbA1c < 7% (odds ratio: 2.21, 1.87 to 2.60). Hypoglycemic events and people experiencing hypoglycemia were not different between 2 groups. Conclusions Initial combination of metformin plus a low hypoglycemic risk antidiabetic drug may achieve better glycemic control, without a rise in hypoglycemia, in patients with untreated T2DM.