Which diabetes drug classes carry a higher risk of hypoglycemia when used alone?

• A. GLP-1 receptor agonists
• B. Sulfonylureas and meglitinides
• C. SGLT2 inhibitors
• D. DPP-4 inhibitors

Answer: (B)

The key idea is how each drug class affects insulin levels relative to blood glucose. Drugs that directly stimulate the pancreas to release insulin, regardless of current glucose, carry a higher hypoglycemia risk when used alone. Sulfonylureas and meglitinides do exactly this: theyClose the potassium channels in beta cells, prompting insulin release even if blood glucose is already low. If meals are skipped or dosing isn’t matched to intake, that extra insulin can push glucose too far down.

The other classes rely more on glucose-dependent or indirect effects. GLP-1 receptor agonists boost insulin release only in the presence of elevated glucose and slow gastric emptying, which lowers the chance of hypoglycemia on their own. SGLT2 inhibitors work by causing glucose to be excreted in the urine, not by increasing insulin, so hypoglycemia is uncommon with monotherapy. DPP-4 inhibitors raise incretin levels to enhance glucose-dependent insulin secretion, also reducing hypoglycemia risk when used alone.

So the higher risk of hypoglycemia on their own belongs to the insulin-secretion–stimulating agents—the ones that cause insulin release irrespective of glucose.