Safety and cardiometabolic efficacy of novel antidiabetic drugs.

INTRODUCTION: This paper encompasses a summary of the safety and cardiometabolic efficacy of novel antidiabetic drugs. 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 outcomes trials from 2008 to 2021 was conducted on Pubmed.gov. Based on 2008 guidance from the US Food and Drug Administration, a non-inferiority margin of 1.8 for the upper bound of the 95% confidence interval (CI) of the hazard ratio (HR) was used in all of the trials and studies reviewed.

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). Whereas, 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 also did not demonstrate an increase in major CV events, with 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.