Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial

Aims: To investigate the efficacy and tolerability of empagliflozin added to basal insulin-treated type 2 diabetes. Methods: Patients inadequately controlled [glycated haemoglobin (HbA1c) >7 to <= 10% (>53 to <= 86 mmol/mol)] on basal insulin (glargine, detemir, NPH) were randomized to empagliflozin 10 mg (n=169), empagliflozin 25 mg (n=155) or placebo (n=170) for 78weeks. The baseline characteristics were balanced among the groups [mean HbA1c 8.2% (67 mmol/mol), BMI 32.2 kg/m(2)]. The basal insulin dose was to remain constant for 18weeks, then could be adjusted at investigator's discretion. The primary endpoint was change from baseline in HbA1c at week 18. Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78. Results: At week 18, the adjusted mean +/- standard error changes from baseline in HbA1c were 0.0V0.1% (-0.1 +/- 0.8 mmol/mol) for placebo, compared with -0.6 +/- 0.1% (-6.2 +/- 0.8 mmol/mol) and -0.7 +/- 0.1% (-7.8 +/- 0.8 mmol/mol) for empagliflozin 10 and 25 mg, respectively (both p<0.001). At week 78, empagliflozin 10 and 25 mg significantly reduced HbA1c, insulin dose and weight vs placebo (all p<0.01), and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo (p=0.004). Similar percentages of patients had confirmed hypoglycaemia in all groups (35-36%). Events consistent with urinary tract infection were reported in 9, 15 and 12% of patients on placebo, empagliflozin 10 and 25 mg, and events consistent with genital infection were reported in 2, 8 and 5%, respectively. Conclusions: Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo.