**Question:** A 75-yrs-old woman with diabetes is taking an oral antidiabetic drugs. One day she goes without eating for 18 h. Her serum glucose concentration is 48 mg/dL (hypoglycemic) upon arrival at the emergency department, where she is deemed to be in critical condition. Which of the following drugs most likely aggravated this fasting hypoglycemia?

A. Glipizide
B. Glyburide
C. Metformin
D. Sitagliptin

**Core Concept:**

The question is discussing hypoglycemia in a patient with diabetes who is on oral antidiabetic drugs (OADs). OADs are medications used to manage blood glucose levels in patients with diabetes. These drugs are classified into various groups according to their mechanism of action: sulfonylureas, biguanides, thiazolidinediones, alpha glucosidase inhibitors, and DPP-4 inhibitors.

**Why the Correct Answer is Right:**

Among the given OADs, the drug that most likely aggravated the patient's fasting hypoglycemia is **Glipizide**. Glipizide is a sulfonylurea, which is a class of medications that stimulate the pancreas to produce more insulin. In this case, the patient is already on an oral antidiabetic drug and is fasting for 18 hours, which is a significant period for an elderly patient. This prolonged fasting causes a decrease in blood glucose levels, and the addition of a sulfonylurea like Glipizide further lowers blood glucose levels, leading to severe hypoglycemia (low blood sugar).

**Why Each Wrong Option is Incorrect:**

- **Glyburide:** Glyburide is also a sulfonylurea. The same explanation applies to Glyburide as it is another sulfonylurea drug.

- **Metformin:** Metformin is a biguanide, another class of oral antidiabetic drugs that work by reducing hepatic glucose production and increasing insulin sensitivity. Unlike sulfonylureas, Metformin is less likely to cause hypoglycemia as it does not stimulate insulin production.

- **Sitagliptin:** Sitagliptin is a DPP-4 inhibitor, which works by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4), leading to increased levels of incretins (GLP-1 and GIP), which improve insulin sensitivity and reduce glucagon secretion. Sitagliptin is less likely to cause hypoglycemia compared to sulfonylureas, as it does not stimulate insulin production.

In conclusion, the correct answer (Glipizide) is chosen due to its mechanism of action, which involves stimulating insulin production, while the wrong options (Glyburide, Metformin, and Sitagliptin) belong to different classes of oral antidiabetic drugs that do not cause hypoglycemia as much as sulfonylureas do.

**Clinical Pearls:**

1. In patients with diabetes, it is essential to consider the patient's age, duration of fasting, and the type