What is the first-line drug to start in type 2 diabetes mellitus?

• A. Metformin
• B. Glipizide
• C. Acarbose
• D. Pioglitazone

Answer: (A)

Metformin is chosen first because it lowers blood glucose effectively with a very favorable safety profile. It mainly works by reducing glucose production in the liver and improving insulin sensitivity in muscle, which translates to meaningful HbA1c reductions without causing hypoglycemia when used alone. It also tends to be weight-neutral or even associated with modest weight loss and is inexpensive, making it a practical starting option for most people with type 2 diabetes. Guidelines typically endorse it as initial therapy unless there are contraindications such as significant kidney disease, where dosing or use may be limited due to the risk of lactic acidosis.

The other drugs have different trade-offs. A sulfonylurea increases insulin secretion but carries a higher risk of hypoglycemia and weight gain, which makes it less ideal as first-line. An alpha-glucosidase inhibitor like acarbose has modest efficacy and notable GI side effects, so it’s rarely the starting choice. A thiazolidinedione such as pioglitazone improves insulin sensitivity but can cause weight gain, edema, and cardiovascular or fracture risks, limiting its desirability as initial therapy.