Cardiovascular Protection with Anti-hyperglycemic Agents
Abstract
Diabetes mellitus is a major risk factor for cardiovascular (CV) disease. Conversely, CV disease is responsible for a majority of the deaths in patients with diabetes. Many drug trials have concentrated on blood glucose (hemoglobin A1c) reduction. This strategy, while reducing microvascular outcomes like nephropathy and neuropathy, has little or no effect on reducing macrovascular events like heart attack, stroke, and heart failure. It has been postulated that hypoglycemia may counterbalance some of the beneficial effects of anti-hyperglycemic agents, but this is not proven. Further, trial evidence for thiazolidinediones (rosiglitazone and pioglitazone) showed increased risk of heart failure and raised concerns about increased myocardial infarction. This heightened awareness of potentially harmful CV effects of otherwise effective hypoglycemic drugs resulted in regulatory mandates for CV outcome trials to ascertain the safety of newer anti-hypoglycemic agents appearing on the market. Three new classes of anti-hyperglycemic agents have been introduced in recent years. While dipeptidyl peptidase-4 (DPP-4) inhibitors exhibited increased heart failure hospitalization in the SAVOR-TIMI 53 trial evaluating saxagliptin and in the secondary analysis of the EXAMINE trial for alogliptin, the effects of glucagon-like peptide-1 (GLP-1) analogs and sodium-glucose co-transporter-2 (SGLT2) inhibitors on CV outcomes in diabetes have largely been positive. The LEADER and SUSTAIN-6 trials…
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