Assessing the Safety of Glucose-Lowering Drugs — A New Focus for the FDA

This article outlines the FDA’s evolving strategy for evaluating the safety of glucose-lowering medications for type 2 diabetes. Following concerns over cardiovascular risks with older drugs like rosiglitazone, the FDA's 2008 guidance prioritized large-scale trials targeting major adverse cardiovascular events (MACE). While this approach yielded valuable safety data and insights, no new drug has since been shown to increase cardiovascular risk and some have demonstrated reduced risk. As a result, the FDA now proposes a broader safety evaluation paradigm. Sponsors are encouraged to include diverse, high-risk populations such as patients with chronic kidney disease (CKD), cardiovascular disease (CVD), and older adults in phase 3 trials, with minimum thresholds for participant-years of drug exposure. Rather than narrowly focusing on cardiovascular risk margins, the revised framework emphasizes robust premarketing safety databases capable of evaluating a wider array of clinical risks. The shift reflects a commitment to patient-centered, generalizable, and efficient regulatory science in diabetes drug development.

This article outlines the FDA’s evolving strategy for evaluating the safety of glucose-lowering medications for type 2 diabetes. Following concerns over cardiovascular risks with older drugs like rosiglitazone, the FDA's 2008 guidance prioritized large-scale trials targeting major adverse cardiovascular events (MACE). While this approach yielded valuable safety data and insights, no new drug has since been shown to increase cardiovascular risk and some have demonstrated reduced risk. As a result, the FDA now proposes a broader safety evaluation paradigm. Sponsors are encouraged to include diverse, high-risk populations such as patients with chronic kidney disease (CKD), cardiovascular disease (CVD), and older adults in phase 3 trials, with minimum thresholds for participant-years of drug exposure. Rather than narrowly focusing on cardiovascular risk margins, the revised framework emphasizes robust premarketing safety databases capable of evaluating a wider array of clinical risks. The shift reflects a commitment to patient-centered, generalizable, and efficient regulatory science in diabetes drug development.