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

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

doi:10.1002/ejhf.1146

Cited by 99 publications

(94 citation statements)

References 37 publications

(39 reference statements)

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“…Previously we showed that, among patients with concurrent HFrEF and diabetes, those treated with insulin have worse symptoms, more signs of congestion and greater risks of death and HF hospitalization compared with those not on insulin . We believe our present report is the first to extend these observations to patients with HFpEF, and we have also identified additional, novel findings in this HF phenotype.…”

Section: Discussionsupporting

confidence: 72%

“…Theoretically, insulin may be detrimental to patients with concomitant HF, but this has yet to be tested in a randomized clinical trial in patients with established HF. In a post‐hoc analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) trial, insulin therapy was associated with higher risks of mortality and HF hospitalization in patients with HF and reduced ejection fraction (HFrEF) and similar findings have been reported from other HFrEF clinical trials . Likewise, adverse outcomes associated with insulin treatment were observed in HF patients included in a large administrative registry from Italy .…”

Section: Introductionsupporting

confidence: 61%

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Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction

Shen

Rørth

Cosmi³

et al. 2019

European J of Heart Fail

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Aims Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). Methods and results We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM‐Preserved (left ventricular ejection fraction ≥ 45%), I‐Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N‐terminal pro‐B‐type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end‐diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient‐years in patients without diabetes, and 10.2 and 17.1 per 100 patient‐years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin‐treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23–1.63, P < 0.001]. The adjusted HR is 1.67 (95% CI 1.20–2.32, p = 0.002) for sudden death (insulin‐treated diabetes vs. other diabetes). Conclusions Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose‐lowering treatments in HF needs to be evaluated in clinical trials.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionsupporting

confidence: 61%

Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction

Shen

Rørth

Cosmi³

et al. 2019

European J of Heart Fail

Self Cite

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“…Although metformin had become the most commonly used drug among patients with mild HF by 2017 (62.8%), the most commonly prescribed agent for patients with moderate‐severe HF was insulin (used in 43.1% of cases). Insulin may not appear to be the preferred agent in this population as insulin can cause fluid retention and hypoglycaemia, leading to adverse cardiovascular outcomes . However, it is possible that this observation is confounded by renal impairment, as more severe HF and higher diuretic requirement may be the cause or result of lower glomerular filtration rate, leading to prescriber hesitation regarding the use of metformin.…”

Section: Discussionmentioning

confidence: 99%

Twelve‐year trends in pharmacologic treatment of type 2 diabetes among patients with heart failure in the United States

Dawwas

Leonard

Garg

et al. 2020

Diabetes Obesity Metabolism

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We conducted a cross‐sectional analysis using a database from commercial health plans in the United States to describe trends in the use of antidiabetic medications among patients with type 2 diabetes and heart failure (HF) from 2006 through 2017. We used loop diuretic dose as a surrogate for HF severity (mild HF 0‐40 mg/day, moderate‐severe HF >40 mg/day). We assessed antidiabetic medication dispensing in the 90 days following HF diagnosis. Over the 12‐year period, we identified an increase in the use of metformin (39.2% vs. 62.6%), dipeptidyl peptidase‐4 inhibitors (DPP‐4i) (0.5% vs. 17.1%) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2i) (0.0% vs. 9.0%), but a decrease in the use of sulphonylureas (47.8% vs. 27.8%) and thiazolidinediones (TZDs) (31.7% vs. 5.3%). In 2017, patients with moderate‐severe HF more commonly used insulin (43.1%); a majority of mild HF patients used metformin (62.8%). A proportion of patients with moderate‐severe HF used TZDs (4.4%). Among patients with diabetes and HF, the use of metformin and DPP‐4i rapidly increased, but a proportion of patients with moderate‐severe HF continued to use TZDs. Despite their promising cardiovascular safety profile, SGLT‐2i use remains limited.

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“…Antidiabetic treatment has a major effect on outcomes . Insulin may cause sodium retention and hypoglycaemia and its use has been associated with worse outcomes in patients with HF with reduced ejection fraction (HFrEF) . Shen et al .…”

Section: Co‐morbiditiesmentioning

confidence: 99%

August 2019 at a glance: arrhythmogenic cardiomyopathy, biomarkers of inflammation, insulin treatment, initiation of sacubitril/valsartan, and pharmacy‐based intervention to increase medication adherence

Metra

2019

European J of Heart Fail

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

Abstract: 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.

Cited by 99 publications

References 37 publications

Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction

Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction

Twelve‐year trends in pharmacologic treatment of type 2 diabetes among patients with heart failure in the United States

August 2019 at a glance: arrhythmogenic cardiomyopathy, biomarkers of inflammation, insulin treatment, initiation of sacubitril/valsartan, and pharmacy‐based intervention to increase medication adherence

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