Efficacy and safety of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as monotherapy or add-on to metformin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

AimsTo compare the efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) as monotherapy or add-on to metformin (Met) in patients with type 2 diabetes mellitus (T2DM). Materials and Methods PubMed, Embase and sites were systematically searched for randomized controlled trials to assess the efficacy and safety of DPP-4is and SGLT-2is in patients with T2DM. Risk ratio (RR) and weighted mean difference (WMD) were used to evaluate outcomes. ResultsIn the analysis of 25 randomized trials, which involved 14619 patients, SGLT-2is were associated with a significantly stronger reduction in haemoglobin A1c (HbA1c) (WMD 0.13%, 95% credible interval [CI], 0.04%-0.22%, P=.005) and fasting plasma glucose (FPG) (WMD 0.80mmol/L, 95% CI, 0.58-1.01mmol/L, P<.00001) than were DPP-4is. However, no significant difference between the 2 drug categories was found in the risk of hypoglycaemic events (RR, 0.99; 95% CI, 0.78-1.26, P=.92). SGLT-2is plus Met was associated with a more significant decrease in FPG (WMD 0.71mmol/L, 95% CI, 0.43-1.00mmol/L, P<.00001) than was DPP-4is plus Met. However, no differences were found in the reduction of HbA1c (WMD 0.11%, 95% CI, -0.03%-0.25%, P=.12) or the risk of hypoglycaemic events (RR, 1.02; 95% CI, 0.80-1.31, P=.86). ConclusionsThis review revealed that, compared to DPP-4is, SGLT-2is significantly reduced HbA1c, FPG and body weight without increasing the risk of hypoglycaemia in diabetes treatment.