Cardiometabolic Effects of a New Class of Antidiabetic Agents

Within the past decade, many new classes of drugs have received approval from the US Food and Drug Administration for treatment of type 2 diabetes mellitus, including glucagon-like peptide-1agonists, dipeptidyl peptidase-4 inhibitors, and the sodium-glucose cotransporter-2 inhibitors. Many trials have been performed, and several more are currently ongoing to evaluate these drugs. This review addresses the broad therapeutic and pleiotropic effects of these drugs. The review also discusses the role of these drugs in the treatment paradigm for type 2 diabetes and identifies patients who would be suitable candidates for treatment with these drugs.

In this comprehensive evidence-based review, the following databases were searched from 1990 to the present: PubMed/MEDLINE, Scopus, CINAHL, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Portal, and the American Diabetes Association and European Association for the Study of Diabetes abstract databases. Randomized clinical trials (RCTs) were only included for the main therapeutic and cardiovascular (CV) effects of these drug classes. For pleiotropic effects, RCTs were included unless no RCTs exist, in which case other studies as specified in the detailed Methods section were included.

All 3 drug classes are effective in lowering hemoglobin A1c between 0.4% and 1.4%, depending on the drug class and population selected. These drug classes have beneficial effects on CV risk factors, such as weight, lipids, and blood pressure, in addition to lowering blood glucose levels. The CV tolerability of some drugs has been evaluated and found to be neutral; however, most trials are currently ongoing to assess CV tolerability. There are no concrete guidelines to determine where these drugs fit in the diabetes management paradigm, and there are ongoing trials to determine the best combination drug with metformin.

These 3 drug classes will potentially increase the armamentarium against hyperglycemia. However, the specific combinations with other antidiabetic drugs and populations that will best benefit from these drugs are still being tested. Future research is also being conducted on the use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in patients with type 1 diabetes.