Canagliflozin acts by
**Core Concept**
Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, which implies that it works by inhibiting the reabsorption of glucose in the kidneys. This results in increased glucose excretion in the urine, thereby reducing blood glucose levels.
**Why the Correct Answer is Right**
Canagliflozin specifically targets SGLT2, a protein responsible for glucose reabsorption in the proximal convoluted tubule of the nephron. By inhibiting SGLT2, canagliflozin reduces the amount of glucose reabsorbed by the kidneys, leading to increased glucose excretion in the urine. This action does not stimulate insulin release or depend on beta-cell function, making it a unique mechanism of action among antidiabetic agents.
**Why Each Wrong Option is Incorrect**
**Option A:** Incorrect because SGLT1 is primarily responsible for glucose reabsorption in the small intestine, not the kidneys.
**Option B:** Incorrect because metformin works by decreasing hepatic glucose production and increasing insulin sensitivity, not by inhibiting glucose reabsorption in the kidneys.
**Option C:** Incorrect because GLP-1 receptor agonists stimulate insulin release and decrease glucagon levels, but do not directly inhibit glucose reabsorption in the kidneys.
**Clinical Pearl / High-Yield Fact**
Canagliflozin and other SGLT2 inhibitors are associated with a reduced risk of hospitalization for heart failure, making them a valuable option for patients with type 2 diabetes and cardiovascular disease.
**Correct Answer:** C.