Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert their antihyperglycemic effect by directly targeting the kidneys. They selectively block the SGLT2 protein located in the proximal convoluted tubules. This inhibition prevents the reabsorption of filtered glucose from the tubular fluid back into the bloodstream. Consequently, excess glucose is excreted in the urine (glucosuria), leading to a reduction in plasma glucose concentrations. This mechanism of action is independent of insulin secretion or sensitivity, focusing solely on renal glucose handling.

A. Sulfonylureas: Act primarily on the pancreatic beta cells to stimulate insulin secretion.

B. Alpha-Glucosidase Inhibitors: Work in the brush border of the small intestine to delay carbohydrate absorption.

C. DPP4 Inhibitors: Prevent the breakdown of incretin hormones (like GLP-1), which act on the pancreas to enhance glucose-dependent insulin secretion.

D. Glucagon-like peptide-1 receptor agonists: Mimic incretin hormones, acting on the pancreas, brain, and gastrointestinal tract.

E. Thiazolidinediones: Increase insulin sensitivity in peripheral tissues, primarily adipose tissue, skeletal muscle, and the liver.

F. Biguanide: Primarily decreases hepatic glucose production and increases insulin sensitivity in peripheral tissues.

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