Introduction & Objective: The combination of metformin (met) with other oral antidiabetic drugs (OADs) like sodium-glucose cotransporter-2 inhibitors (SGLT-2i) is recommended by international guidelines for type 2 diabetes mellitus treatment. This systematic literature review (SLR) and meta-analysis (MA) compared the efficacy and safety specifically of dual therapy with SGLT-2i versus other OADs as add-on to met.
Methods: An update to a 2016 SLR was conducted to identify randomized controlled trials (RCTs) comparing dual therapies of OADs + met. Searches of MEDLINE, Embase, the Cochrane Library, recent congresses and SLR bibliographies were conducted in May 2023. RCTs were assessed using the Cochrane Risk of Bias tool. MAs employing random effect models compared change in haemoglobin A1c (HbA1c) and adverse events with SGLT-2i versus other OADs as add-on to met at Week 52.
Results: A total of 23 RCTs comprising of 11,911 patients on oral met-containing dual therapies (SGLT-2is, dipeptidyl peptidase-4 inhibitors, oral glucagon-like peptide-1 receptor agonists and sulfonylureas) were included. The mean difference (MD) in change from baseline of HbA1c with SGLT-2i + met versus other OADs + met was comparable (MD 0.01, 95% confidence interval [CI] -0.16-0.18). In terms of safety, SGLT-2i + met had a significantly lower risk of hypoglycaemia (risk ratio [RR] 0.27, 95% CI 0.09-0.84) and lower risk of myocardial infarction (MI) (RR 0.58, 95% CI 0.16-2.07) than other OADs + met. However, risk of urinary tract infection (UTI) was higher (RR 1.22, 95% CI 0.94-1.58).
Conclusion: Compared with other OADs + met dual therapies, SGLT-2i + met exhibited noninferior efficacy and significantly reduced risk of hypoglycaemia while risks of MI and UTI were not significantly different. Results from this study reinforce the recommendation of dual therapy in international guidelines, depending on patients’ treatment goals and risk profiles.
Y. Ma: None. Y. Lin: None. X. Ding: None. Y. Peng: None.
