A 65-year-old male with Type 2 diabetes mellitus takes metformin (Glucophage®). Each of the following describes a mechanism of action of metformin EXCEPT one. Which is the EXCEPTION?

Correct answer: D. Increases glucagon production

• A. INCORRECT (this IS a metformin mechanism). Metformin increases insulin sensitivity in peripheral tissues, particularly muscle and fat, helping glucose enter cells more effectively without requiring additional insulin secretion.
• B. INCORRECT (this IS a metformin mechanism). Metformin's primary mechanism is inhibition of hepatic gluconeogenesis (glucose production from non-carbohydrate sources), which is the main contributor to fasting hyperglycemia in Type 2 diabetes.
• C. INCORRECT (this IS a metformin mechanism). Metformin reduces glucose absorption from the intestinal tract, contributing to its overall glucose-lowering effect.
• D. CORRECT — this is the EXCEPTION. Metformin does NOT increase glucagon production. In fact, metformin decreases glucagon production and its hepatic effects. Glucagon is a hormone that promotes glucose release from the liver; metformin suppresses glucagon signaling as part of its mechanism. Agents like GLP-1 receptor agonists reduce glucagon; metformin also indirectly reduces glucagon's effects.