Which of the following drugs used to treat type II diabetes mellitus causes weight loss:
**Core Concept**
Metformin is a biguanide that improves insulin sensitivity in peripheral tissues and reduces hepatic glucose production without causing hypoglycemia. Unlike sulfonylureas, it does not stimulate insulin secretion and has a unique mechanism of action that contributes to weight neutrality or modest weight loss.
**Why the Correct Answer is Right**
Metformin decreases glucose production in the liver and enhances insulin sensitivity in muscle and adipose tissue. It also reduces appetite and alters gut microbiota, leading to decreased caloric absorption and modest weight loss. This effect is particularly notable in patients with obesity or insulin resistance. Unlike sulfonylureas (e.g., glimepiride, repaglinide, gliclazide), which promote insulin secretion and can lead to weight gain due to increased insulin levels, metformin does not stimulate insulin release and is associated with weight loss in clinical practice.
**Why Each Wrong Option is Incorrect**
Option B: Glimepiride is a sulfonylurea that stimulates insulin secretion, leading to increased insulin levels and weight gain, not loss.
Option C: Repaglinide, another meglitinide, acts similarly to sulfonylureas by promoting insulin release and is associated with weight gain.
Option D: Gliclazide, a second-generation sulfonylurea, also increases insulin secretion and is linked to weight gain due to hyperinsulinemia.
**Clinical Pearl / High-Yield Fact**
Metformin is the only antidiabetic agent commonly used in type II diabetes that consistently causes or is associated with weight loss; all sulfonylureas and meglitinides promote weight gain due to insulin stimulation. This makes metformin a preferred first-line agent in patients with obesity or metabolic syndrome.
✓ Correct Answer: A. Metformin