Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes

Franco Cosmi, Li Shen, Michela Magnoli, William T. Abraham, Inder S. Anand, John G. Cleland, Jay N. Cohn, Deborah Cosmi, Giorgia De Berardis, Kenneth Dickstein, Maria Grazia Franzosi, Lars Gullestad, Pardeep S. Jhund, John Kjekshus, Lars Køber, Vito Lepore, Giuseppe Lucisano, Aldo P. Maggioni, Serge Masson, John J.V. McMurrayAntonio Nicolucci, Vito Petrarolo, Fabio Robusto, Lidia Staszewsky, Luigi Tavazzi, Roberto Teli, Gianni Tognoni, John Wikstrand, Roberto Latini

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine–Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case–control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16–1.38), for HF hospitalization 1.23 (1.13–1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87–2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32–1.53). Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)888-895
Number of pages8
JournalEuropean Journal of Heart Failure
Issue number5
StatePublished - May 2018

Bibliographical note

Funding Information:
We thank Antonio D'Ettorre (CORESEARCH, Centre for Outcomes Research and Clinical Epidemiology, Pescara, Italy) for treatment and data management of the administrative database of the Puglia Region; Lucia Bisceglia and Ettore Attolini (Regional Health Agency of Puglia, Italy) for having provided all the necessary data with great readiness. We also thank the Regional Health Agency (Giovanni Gorgoni) and the Department of Health (Giancarlo Ruscitti) of the Puglia Region for the cooperation and general interest. Conflict of interest: none declared.

Publisher Copyright:
© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology


  • Diabetes mellitus
  • Heart failure
  • Insulin


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