Comparison of the clinical effect of empagliflozin on glycemic and non-glycemic parameters in Japanese patients with type 2 diabetes and cardiovascular disease treated with or without baseline metformin

BACKGROUND: The most recent treatment guidelines for type 2 diabetes (T2D) recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors should be considered preferentially in patients with T2D with either a high cardiovascular risk or with cardiovascular disease (CVD), regardless of their diabetes status and prior use of conventional metformin therapy. Whether the therapeutic impact of SGLT2 inhibitors on clinical parameters differs according to the use of metformin therapy however remains unclear. METHODS: The study was a post hoc analysis of the EMBLEM trial (UMIN000024502). All participants (n = 105; women 31.4%; mean age 64.8 years) had both T2D and CVD and were randomized to either 24 weeks of empagliflozin 10 mg daily or placebo. Analysis of the data assessed the effect of empagliflozin on changes from baseline to 24 weeks in glycemic and non-glycemic clinical parameters, according to the baseline use of metformin. RESULTS: Overall, 53 (50.5%) patients received baseline metformin. In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the decrease in systolic blood pressure from baseline levels was greater in patients receiving metformin, compared to that observed in metformin-naïve patients (group difference − 8.5 [95% confidence interval (CI) − 17.7 to 0.6 mmHg], p = 0.066). Reduction in body mass index (BMI) was significantly greater in patients receiving baseline metformin, relative to nonusers (− 0.54 [95% CI − 1.07 to − 0.01] kg/m(2), p = 0.047). The group ratio (baseline metformin users vs. nonusers) of proportional changes in the geometric mean of high-sensitivity Troponin-I (hs-TnI) was 0.74 (95% CI 0.59 to 0.92, p = 0.009). No obvious differences were observed in glycemic parameters (fasting plasma glucose, glycohemoglobin, and glycoalbumin) between the baseline metformin users and nonusers. CONCLUSION: Our findings suggest 24 weeks of empagliflozin treatment was associated with an improvement in glycemic control, irrespective of the baseline use of metformin therapy. The effects of empagliflozin on reductions in BMI and hs-TnI were more apparent in patients who received baseline metformin therapy, compared to that observed in metformin-naïve patients. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502