Comparing SGLT2i and Other Oral Antidiabetic Drugs as Dual Therapy Add‐On to Metformin in Type 2 Diabetes: A Systematic Review and Meta‐Analysis

TL;DR

This study compares the effectiveness and safety of SGLT2 inhibitors plus metformin to other diabetes drugs in managing type 2 diabetes.

Contribution

The study provides updated evidence on the comparative efficacy and safety of SGLT2 inhibitors versus other oral diabetes therapies when combined with metformin.

Findings

SGLT2 inhibitors plus metformin had similar HbA1c reduction as other oral diabetes therapies.

SGLT2 inhibitors plus metformin showed lower hypoglycaemia risk and greater weight loss.

SGLT2 inhibitors plus metformin had a higher risk of genital infections compared to other therapies.

Abstract

To compare up‐to‐date efficacy and safety data of sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is) versus other metformin‐containing oral dual‐therapies (ODTs) in type 2 diabetes mellitus.

We updated a 2016 systematic literature review (SLR), searching MEDLINE, Embase, the Cochrane Database of Systematic Reviews, congress abstracts and SLR/meta‐analysis (MA) bibliographies to identify randomised controlled trials. Two independent reviewers determined eligible studies, which were extracted and assessed using the Cochrane Risk of Bias tool. MA was conducted using random‐effects pairwise models.

We included 36 publications (23 unique studies). Mean differences (MD) indicated comparable change in HbA1c from baseline at Weeks 24 and 52 between SGLT‐2i plus metformin and other metformin‐containing ODTs. Patients on SGLT‐2i plus metformin showed a significantly lower risk of hypoglycaemia (risk ratio [RR]: 0.27, 95% CI: 0.09, 0.84) and significantly greater weight reduction (MD: –2.59; 95% CI: −4.42, −0.77), but an elevated risk of genital infection (RR: 5.08; 95% CI: 3.49, 7.38) at Week 52 compared with other ODTs. Other safety outcomes (e.g., urinary tract infections) were comparable between SGLT‐2i plus metformin and other ODTs.

Compared with other ODTs, SGLT‐2i plus metformin exhibited overall comparable efficacy and safety, with a lower risk of hypoglycaemia and greater weight reduction at Week 52.

This systematic literature review and meta‐analysis compared sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is) against other metformin‐containing oral dual‐therapies (ODTs) in type 2 diabetes mellitus. SGLT‐2i plus metformin exhibited overall comparable efficacy and safety, with a lower risk of hypoglycaemia and greater weight reduction than other ODTs at Week 52.

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