High‐dose sodium‐glucose co‐transporter‐2 inhibitors are superior in type 2 diabetes: A meta‐analysis of randomized clinical trials

AIM: To determine the overall efficacy of high- versus low-dose sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D). MATERIAL AND METHODS: A literature search using MEDLINE, EMBASE and the Cochrane Library was performed from 1 January 2006 to 23 September 2020. Random effects models were used to calculate mean differences (MDs) and pooled relative risk (RR). Prespecified subgroup analyses for each SGLT2 inhibitor, follow-up and controls were performed. Leave-one-out sensitivity and meta-regression analyses were conducted. RESULTS: A total of 51 randomized controlled trials involving 23 989 participants (weighted mean age, 58.9 years; men, 58.8%) were eligible for our meta-analysis. For glycaemic regulation ability, a significant reduction in HbA1c (MD -0.080%, 95% confidence interval [CI] -0.100 to -0.060), fasting plasma glucose (MD -0.227 mmol/L, 95% CI -0.282 to -0.173) and postprandial plasma glucose (MD -0.834 mmol/L, 95% CI -1.268 to -0.400) levels was observed in the high-dose SGLT2 inhibitor group. Treatment with high-dose SGLT2 inhibitors enabled easier achievement of the target (HbA1c <7%) than low-dose SGLT2 inhibitors (RR 1.148, 95% CI 1.104 to 1.193). High-dose SGLT2 inhibitor-based treatment resulted in more efficient regulation of body weight and blood pressure (body weight: MD -0.346 kg, 95% CI -0.437 to -0.254; systolic blood pressure: MD -0.583 mmHg, 95% CI -0.903 to -0.263; diastolic blood pressure: MD -0.352 mmHg, 95% CI -0.563 to -0.142). The results were similar in sensitivity analyses. CONCLUSIONS: The overall efficacy of SGLT2 inhibitors, mainly canagliflozin, dapagliflozin and empagliflozin, was found to be dose dependent.