Empagliflozin facilitates sustained insulin dose reductions in patients with type 2 diabetes and cardiovascular disease: the EMPA-REG OUTCOME trial

Background Many patients with T2 D require insulin therapy and reducing insulin requirements is attractive to both patients and practitioners. Limited data are available regarding the effects of SGLT-2 inhibitor initiation on background insulin doses.

Methods In EMPA-REG OUTCOME, 7,020 patients were treated with empagliflozin (EMPA) 10, 25 mg, or placebo (PBO). This analysis focuses on the 3,387 (48 %) patients treated with insulin at baseline. After the first 12 weeks, changes in background antihyperglycemic therapy were permitted. We assessed treatment effects of pooled EMPA arms vs. PBO on time to sustained total daily insulin dose reduction from baseline by 10 %, 20 %, and 30 % for at least 2 consecutive study visits by Cox regression adjusting for baseline risk factors. Dose reductions were considered appropriate if they were accompanied by no subsequent change (defined as < 0.2 % increase) or a decrease in subsequent HbA1c.

Results EMPA significantly increased the proportion of patients achieving sustained and appropriate (without increases in HbA1c) insulin dose reductions by > 20 % from baseline compared with PBO after accounting for key covariates (adj. HR 1.87 [95 % CI: 1.39-2.51]; P < 0.0001). Similarly, consistent benefits were observed when considering sustained insulin dose reductions of > 10 % from baseline in EMPA vs. PBO (14.0 % vs. 7.5 %; adj. HR 1.91 [95 % CI: 1.50-2.43]; P < 0.0001) or > 30 % from baseline (5.6 % vs. 3.3 %; adj. HR 1.68 [95 % CI: 1.17-2.43]; P = 0.0055).

Conclusions Among insulin-treated patients with T2 D and CVD, EMPA facilitates meaningful, sustained, and appropriate reductions in insulin requirements.

Publication History

Article published online:
06 May 2021