Effects of empagliflozin on insulin initiation or intensification in patients with type 2 diabetes and cardiovascular disease: findings from the EMPA‐REG OUTCOME ® trial

Vaduganathan, M. et al. (2021) Effects of empagliflozin on insulin initiation or intensification in patients with type 2 diabetes and cardiovascular disease: findings from the EMPA‐REG OUTCOME ® trial. Diabetes, Obesity and Metabolism, 23(12), pp. 2775-2784. (doi: 10.1111/dom.14535) (PMID:34463409)

Abstract

Aims: Insulin use in type 2 diabetes, while often necessary, is associated with hypoglycemia and weight gain, requires training, and may add significant costs. We evaluated the effects of empagliflozin versus placebo on subsequent insulin initiation or dosing changes in a large cardiovascular outcomes trial. Materials and Methods: In EMPA-REG OUTCOME®, 7,020 patients with type 2 diabetes and cardiovascular disease received empagliflozin 10mg, 25mg, or placebo. Median follow-up was 3.1 years. After 12 weeks’ treatment, changes in background antihyperglycemic therapy were permitted. Among insulin-naïve patients, we assessed effects of pooled empagliflozin arms vs. placebo on time to initiation of insulin. Among insulin-treated patients, we assessed effects on time to increase or decrease in insulin dose >20%. Results: In 3,633 (52%) participants not treated with insulin at baseline, empagliflozin reduced new use of insulin vs. placebo by 60% (7.1% vs. 16.4%; adjusted HR 0.40 [95% CI 0.32-0.49]; P<0.0001). In 3,387 (48%) patients using insulin at baseline, empagliflozin reduced need for a >20% insulin dose increase by 58% (14.4% vs. 29.3%; adjusted HR 0.42 [95% CI 0.36-0.49]; P<0.0001) and increased the proportion achieving sustained >20% insulin dose reductions without subsequent increases in HbA1c compared with placebo (9.2% vs. 4.9%; adjusted HR 1.87 [95% CI: 1.39-2.51]; P<0.0001). Sensitivity analyses confirmed consistent findings when insulin dose changes >10% or >30% were considered. Conclusions: In patients with type 2 diabetes and cardiovascular disease, empagliflozin markedly and durably delays insulin initiation and substantial increases in insulin dose while facilitating sustained reductions in insulin requirements over time.

• Item Type: Articles
• Additional Information: The EMPA-REG OUTCOME® trial was sponsored by the Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Vaduganathan, M., Inzucchi, S. E., Sattar, N., Fitchett, D. H., Ofstad, A. P., Brueckmann, M., George, J. T., Verma, S., Mattheus, M., Wanner, C., Zinman, B., and Butler, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetes, Obesity and Metabolism
• Publisher: Wiley
• ISSN: 1462-8902
• ISSN (Online): 1463-1326
• Published Online: 31 August 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Diabetes, Obesity and Metabolism 23(12): 2775-2784
• Publisher Policy: Reproduced under a Creative Commons License