Other oral hypoglycemic agents (e.g. sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors)

Research summary

Human research on sulfonylureas, DPP-4 inhibitors, and SGLT2 inhibitors overwhelmingly involves patients with type 2 diabetes or, less commonly, other dysglycemic conditions. There are almost no trials designed to evaluate benefits in completely healthy, normoglycemic volunteers, and any such studies primarily use healthy subjects to characterize pharmacokinetics, tolerability, and acute hypoglycemic effects rather than to assess long-term health benefits. In these contexts, the drugs reliably lower blood glucose and influence insulin or glucagon dynamics as expected, but in individuals who already have normal glycemic control this is generally a liability rather than a benefit. The consensus in the medical literature is that these agents should be reserved for people with diabetes or closely related metabolic disorders, where their benefits for glycemic control and, for some SGLT2 inhibitors and DPP-4 inhibitors, cardiovascular and renal outcomes clearly outweigh risks. In healthy people, potential harms such as hypoglycemia (particularly with sulfonylureas), genital and urinary infections, dehydration, and rare but serious events like ketoacidosis or severe hypoglycemia dominate the risk–benefit balance. As a result, there is no research-supported indication for using these medications as metabolic or performance-enhancing interventions in otherwise healthy adults.