Safety and cardiometabolic efficacy of novel antidiabetic drugs

ABSTRACT

Introduction

There are three major drug classes discussed in this review: dipeptidyl dipeptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAS), and sodium-glucose cotransporter-2 (SGLT2) inhibitors. A literature review of the landmark cardiovascular outcome trials from 2008 to 2021 was conducted.

Areas covered

The cumulative data shown in this review suggest that in patients with Type 2 Diabetes (T2D), SGLT2 inhibitors and GLP-1 RAS may reduce cardiovascular (CV) risk. Specifically, in the heart failure (HF) population, SGLT2 inhibitors have shown a reduction in hospitalizations in some randomized controlled trials (RCTs). DPP4 inhibitors have not shown a similar reduction in CV risk and even exhibited an increase in hospitalizations for HF in one RCT. It is important to note that the DPP4 inhibitors did not demonstrate an increase in major CV events, with the exception of the increase in HF hospitalizations in the SAVOR TIMI 53 trial.

Expert Opinion

Future avenues of research to explore include the use of novel antidiabetic agents to reduce post-myocardial infarction (MI) CV risk and arrhythmias independent of their use as diabetic agents.

KEYWORDS:

• Cardiovascular safety
• cardiovascular outcome trials
• novel antidiabetic drugs
• dipeptidyl dipeptidase-4 inhibitors
• glucagon-like peptide-1 receptor agonists
• sodium-glucose cotransporter-2 inhibitors
• type 2 diabetes

Article highlights

• DPP4 inhibitors did not demonstrate an increase or reduction in major CV events

• DPP4 inhibitors have exhibited a slight increase in hospitalizations for HF in one RCT.

• SGLT2 inhibitors and GLP-1 RAS may reduce cardiovascular (CV) risk

• Specifically in the heart failure (HF) population, SGLT2 inhibitors have shown a reduction in hospitalizations in many randomized controlled trials (RCTs).

• SGLT2 inhibitors reduce the progression of kidney disease in patients with Type 2 Diabetes

• Expert opinion section highlighting future avenues of research over the next 5 years

Declaration of interests

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.

Author contribution statement

L Michaud: contributed Abstract, Introduction, SGLT-2, GLP1, Conclusion, and Expert Opinion Sections. M Seplowe: contributed DPP4 – I and GLP1 sections. J Meir: contributed Future Directions Section. W Aronow: contributed editing and reference check as well as submitting author

Additional information

Funding

This paper was not funded.