Contemporary choice of glucose lowering agents in heart failure patients with type 2 diabetes

ABSTRACT

Introduction

There is a bi-directional link between type 2 diabetes mellitus (T2DM) and heart failure (HF) and their co-existence markedly increases an individual’s morbidity and mortality. Therefore, it is of major importance to diagnose early (and, even better, prevent) HF in T2DM patients, as well as adequately treat T2DM patients with HF.

Areas covered

The present narrative review discusses the effects of different antidiabetic drugs [metformin, pioglitazone, sulphonylureas (SUs), dipeptidyl peptidase 4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 inhibitors (SGLT2i) and insulin] on HF incidence, hospitalization and outcomes. Current guidelines of diabetes and cardiology societies on this issue are also commented on.

Expert opinion

Metformin (+lifestyle interventions) is the first-line treatment for all T2DM patients and SGLT2i are the preferred drugs (class I, level of evidence A) in patients with T2DM and HF. Pioglitazone is contraindicated in HF, whereas SUs, DPP4i, GLP-1 RAs and insulin are considered as neutral. However, SUs may cause hypoglycemia and weight gain, saxagliptin (a DPP4i) must be avoided in this setting and GLP-1 RAs seem not to affect HF risk. There is an urgent need of increasing guidelines implementation regarding SGLT2i use in clinical practice, to sufficiently tackle the HF burden in T2DM.

KEYWORDS:

• dipeptidyl peptidase 4 inhibitors
• glucagon-like peptide-1 receptor agonists
• heart failure
• insulin
• metformin
• pioglitazone
• sodium-glucose cotransporter 2 inhibitors
• sulphonylureas
• type 2 diabetes mellitus

Article highlights

• Type 2 diabetes mellitus (T2DM) is associated with the development and progression of heart failure (HF), and vice versa.

• The co-existence of T2DM and HF is linked to a very high cardiovascular (CV) risk, leading to increased morbidity and mortality.

• Metformin is the first-line treatment for all T2DM patients, together with lifestyle interventions, and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the preferred drugs (class I, level of evidence A) in patients with T2DM and HF.

• Pioglitazone and saxagliptin are contraindicated in the presence of HF, whereas insulin, sulphonylureas (SUs) and dipeptidyl peptidase 4 inhibitors (DPP4i) are regarded as neutral. However, SUs can cause hypoglycemia and weight gain.

• Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exert several cardiometabolic benefits but seem not to affect HF prevalence and outcomes.

This box summarizes key points contained in the article.

Declaration of interest

N Katsiki has given talks, attended conferences and participated in trials sponsored by Amgen, AstraZeneca, Boehringer Ingelheim, Elpen, Novartis, Novo Nordisk, Sanofi, Servier, and Viatris. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.