Heart failure with insulin degludec versus glargine U100 in patients with type 2 diabetes at high risk of cardiovascular disease: DEVOTE 14

Richard E Pratley, Mansoor Husain, Ildiko Lingvay, Thomas R Pieber, Thomas Mark, Hans A Saevereid, Daniel Vega Møller, Bernard Zinman, DEVOTE Study Group, Richard E Pratley, Mansoor Husain, Ildiko Lingvay, Thomas R Pieber, Thomas Mark, Hans A Saevereid, Daniel Vega Møller, Bernard Zinman, DEVOTE Study Group

Abstract

Background: Heart failure (HF) is a common cardiovascular complication of type 2 diabetes (T2D). This secondary analysis investigated baseline factors and treatment differences associated with risk of hospitalization for HF (hHF), and the possible association between severe hypoglycemia and hHF.

Methods: DEVOTE was a treat-to-target, double-blind cardiovascular outcomes trial in patients (n = 7637) with T2D and high cardiovascular risk randomized to insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). The main endpoint of this secondary analysis was time to first hHF (standardized MedDRA Query definition). Severe hypoglycemia was adjudicated (American Diabetes Association definition). The main endpoint and the temporal association between severe hypoglycemia and hHF were analyzed with a Cox proportional hazards regression model. Predictors of time to first hHF were identified using baseline variables.

Results: Overall, 372 (4.9%) patients experienced hHF (550 events). There was no significant difference in the risk of hHF between treatments (hazard ratio [HR] 0.88 [0.72;1.08]95% CI, p = 0.227). Prior HF (HR 4.89 [3.90;6.14]95% CI, p ≤ 0.0001) was the strongest predictor of future hHF events. The risk of hHF significantly increased after (HR 2.2), and within a week after (HR 11.1), experiencing a severe hypoglycemic episode compared with before an episode.

Conclusions: In patients with T2D and high cardiovascular risk there were no treatment differences in terms of hHF. Prior HF was the strongest predictor of future hHF events, and there was an association between severe hypoglycemia and subsequent hHF. Further research should evaluate whether the risk of hHF can be modified by treatments aimed at reducing hypoglycemia. Trial Registration NCT01959529.

Keywords: Clinical trial; Hospitalization for heart failure; Insulin degludec; Severe hypoglycemia; Type 2 diabetes.

Conflict of interest statement

REP’s fees for services were paid directly to AdventHealth (formerly Florida Hospital), a non-profit organization and therefore he has no financial relationship with the following companies, except for Sanofi. Consultancy and speaker fees from AstraZeneca, Takeda and Novo Nordisk; consultancy fees from Boehringer Ingelheim, GlaxoSmithKline, Hanmi Pharmaceutical Co. Ltd., Janssen Scientific Affairs LLC, Ligand Pharmaceuticals, Inc., Eli Lilly, Merck, Pfizer and Eisai, Inc.; research grant from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals, Inc., Eli Lilly, Merck, Sanofi US LLC and Takeda. MH has received consulting fees or honoraria from AstraZeneca, Boehringer-Ingelheim, Janssen, Merck and Novo Nordisk. IL received funds for research, consulting, editorial support and/or travel expenses from: Novo Nordisk, Eli Lilly, Sanofi, Astra Zeneca, Boehringer-Ingelheim, Merck, Novartis, Intarcia, MannKind, TARGETPharma, Pfizer, Valeritas and Mylan. TRP has received research support from Novo Nordisk and AstraZeneca (paid directly to the Medical University of Graz); personal fees as a consultant from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Novo Nordisk and Roche Diabetes Care. TRP is also the Chief Scientific Officer of CBmed (Center for Biomarker Research in Medicine), a public-funded biomarker research company. HAS and DVM are full-time employees of Novo Nordisk A/S. TM is a full-time employee of, and holds stock in, Novo Nordisk A/S. BZ has received grant support from Boehringer-Ingelheim, AstraZeneca and Novo Nordisk; and consulting fees from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk and Sanofi.

Figures

Fig. 1
Fig. 1
Main and sensitivity analyses of treatment differences in time to first hHF (SMQ definition). *Broad MedDRA search weighted by proportion confirmed in LEADER by the Event Adjudication Committee. There were only 100 events using the broad MedDRA search without the LEADER match, 31 of which were classed as cardiac disorders. CI confidence interval, glargine U100 insulin glargine 100 units/mL, hHF hospitalization for heart failure, HF heart failure, N number of patients, % proportion of patients, SMQ standardized Medical Dictionary for Regulatory Activities Query

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