Understanding the cardiovascular risk with non-insulin antidiabetic drugs

ABSTRACT

Introduction: Diabetes mellitus is a major public health problem with significant macro- and microvascular complications. Achievement of glucose control is associated with a substantial reduction of microvascular events, while the effects of antidiabetic drugs in macro-vascular complications are less clear. This review summarizes and critically discusses the cardiovascular effects of non-insulin antidiabetic agents.

Areas covered: A selective literature search of Pubmed was performed regarding the efficacy and safety of non-insulin antidiabetic agents in randomized controlled clinical trials and relevant meta-analyses. Data are presented for all major classes of antidiabetic drugs: metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 analogues, and SGLT-2 inhibitors. Efficacy and safety were focused on the cardiovascular system.

Expert opinion: Disparities in cardiovascular safety and efficacy between antidiabetic drugs exist. Metformin remains the first-choice drug with proven cardiovascular benefits. The cardiovascular profile of sulfonylureas is yet unclarified, while thiazolidinediones seem to be effective in secondary stroke prevention but heart failure concerns limit their use. The cardiovascular safety of DPP-4 inhibitors has been demonstrated, without however significant morbidity and mortality benefits. SGLT-2 inhibitors and GLP-1 analogues offer significant cardiovascular benefits and are recommended for patients with overt cardiovascular disease.

KEYWORDS:

• Diabetes mellitus
• cardiovascular disease
• cardiovascular risk
• antidiabetic drugs

Article highlights

• Metformin is the cornerstone of the therapeutic algorithm of patients with type 2 diabetes, irrespective of CV status.

• Glitazones and sulphonylureas provided inconsistent results, with some studies suggesting detrimental effects on CV outcomes. Notably, pioglitazone was shown to offer benefits for the secondary prevention of stroke.

• DPP-4 inhibitors are a safe choice in terms of CV events for the therapy of type 2 diabetes

• Liraglutide, empagliflozin, and canagliflozin have provided remarkable reductions in CV morbidity and mortality and are recommended for the management of patients with diabetes and overt CV disease.

• Safety concerns with SGLT-2 inhibitors use are to be verified or put to rest in future studies.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.