Markers of GV have been associated with CV outcomes in type 2 diabetes (T2D), however, the association of GV with HF outcomes remains unclear. In EMPA-REG OUTCOME, empagliflozin reduced the risk of CV death by 38% and HF hospitalizations (HHF) by 35%. Here we explore the association between GV and CV death/HHF outcomes.

In EMPA-REG OUTCOME, 7,020 patients with T2D and established CV disease received placebo (PBO), empagliflozin (EMPA) 10 mg or 25 mg and were observed for a median period of 3.1 years. We defined within-patient GV as range and standard deviation of HbA1c measurements on-treatment until week 28. The associations with CV death, first HHF, and HHF or CV death were explored in PBO and pooled EMPA arms separately with landmark (LM) analyses at week 28 by Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12.

GV levels were lower with EMPA (Table). In the LM analysis, higher GV increased the risk for CV death and CV death or HHF in both treatment arms. For HHF, no significant association could be shown (Table).

In EMPA-REG OUTCOME, EMPA reduced GV. An increase in GV correlated with increased risk of subsequent CV death and CV death or HHF. The association with HHF alone was not significant maybe due to a lower numbers of HHF events, or the assumption that the effects of EMPA on HHF are largely glucose-independent.

graphic
View largeDownload slide
Disclosure

A. Ceriello: Advisory Panel; Self; Abbott Laboratories, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk A/S, Vifor Pharma. Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; A. Menarini Diagnostics, AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim Pharmaceuticals, Inc. A. Ofstad: Employee; Self; Boehringer Ingelheim International GmbH. I. Zwiener: Employee; Self; Boehringer Ingelheim Pharma GmbH & Co KG, Merck KGaA. S. Kaspers: Employee; Self; Boehringer Ingelheim International GmbH. J. George: Employee; Self; Boehringer Ingelheim International GmbH. A. Nicolucci: Consultant; Self; AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S. Research Support; Self; Artsana S.p.A., Dexcom, Inc., Novo Nordisk A/S, Sanofi-Aventis.

Funding

Boehringer Ingelheim; Eli Lilly and Company

© 2019 by the American Diabetes Association.
2019
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.