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.

Interessenskonflikt

MV is supported by the KL2 / Catalyst Medical Research Investigator Training Award from Harvard Catalyst (NIH / NCATS Award UL 1TR002541) and serves on advisory boards for Amgen, AstraZeneca (AZ), Baxter Healthcare, Bayer AG, Boehringer Ingelheim (BI), Cytokinetics, and Relypsa.

NS has consulted for Amgen, BI, Eli Lilly (EL), Napp, Novo Nordisk (NN), Pfizer, and Sanofi, and received grant support from BI.

DF has received financial support from Amgen, AZ, BI, EL, Merck & Co., and Sanofi.

JTG was an employee of BI at the time of this analysis.

SV has received grants and personal fees for speaker honoraria and advisory board participation from AZ, Bayer, BI, Janssen, and Merck. He has received grants and personal fees for advisory board participation from Amgen, grants from Bristol-Myers Squibb, personal fees for speaker honoraria and advisory board participation from EL, NN and Sanofi, and personal fees for speaker honoraria from EOCI Pharmacomm Ltd, Novartis, Sun Pharmaceuticals and Toronto Knowledge Translation Working Group.

APO is employee of BI.

CW has received honoraria for consultancy and lecturing from AZ, Bayer, BI, GlaxoSmithKline, EL and Co., Merck Sharp & Dohme, Mundipharma, Sanofi Genzyme, and Takeda.

SEI has served as a consultant, speaker, or as a member of clinical trial steering committees for BI, AZ, NN, Sanofi / Lexicon Pharmaceuticals, Merck, vTv Therapeutics and Abbott / Alere.

BZ has received financial support from AZ, BI, EL, Janssen, Merck, NN, and Sanofi.

JB reports consulting fees from BI, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NN, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd., and Vifor.

Publication History

Article published online:
06 May 2021