Ertugliflozin

• Type 2 Diabetes Mellitus
• Blood Sugar Control
• Glycemic Management
• SGLT2 Inhibitor Therapy

Ertugliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of type 2 diabetes mellitus. This oral medication improves glycemic control through an insulin-independent mechanism that promotes urinary glucose excretion.

Mechanism of Action

Ertugliflozin selectively and reversibly inhibits sodium-glucose co-transporter 2 (SGLT2), which is located in the proximal renal tubule and is responsible for reabsorbing approximately 90% of the glucose filtered by the kidneys. By blocking SGLT2, ertugliflozin reduces renal glucose reabsorption, lowering the renal threshold for glucose and increasing urinary glucose excretion (glucosuria). This insulin-independent mechanism results in lowered blood glucose levels while also producing caloric loss and osmotic diuresis. Secondary benefits include modest reductions in blood pressure and body weight.

Available Formulations

Ertugliflozin is available as film-coated tablets in 5 mg and 15 mg strengths. It is also available in fixed-dose combination tablets with sitagliptin (Steglujan) and with metformin (Segluromet). The tablets can be taken in the morning with or without food.

Medical Uses

Ertugliflozin is FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It can be used as monotherapy or in combination with other antidiabetic medications including metformin, sulfonylureas, DPP-4 inhibitors, and insulin. Unlike some other SGLT2 inhibitors, ertugliflozin does not have specific cardiovascular or renal outcome indications based on completed cardiovascular outcome trials.

Dosing Guidelines

The recommended starting dose is 5 mg once daily, taken in the morning. The dose may be increased to 15 mg once daily for additional glycemic control. Ertugliflozin should not be initiated in patients with an eGFR less than 30 mL/min/1.73 m², and it is contraindicated in patients on dialysis. When used with insulin or insulin secretagogues, lower doses of those medications may be needed to reduce hypoglycemia risk.

Important Safety Information

SGLT2 inhibitors, including ertugliflozin, have been associated with ketoacidosis, including diabetic ketoacidosis (DKA) with lower than expected glucose levels (euglycemic DKA). Patients should be assessed for ketoacidosis if they present with signs/symptoms regardless of blood glucose level. The medication should be temporarily discontinued before scheduled surgeries. Other serious risks include acute kidney injury, urosepsis and pyelonephritis, hypotension, necrotizing fasciitis of the perineum (Fournier's gangrene), and genital mycotic infections. Lower limb amputations have been reported with SGLT2 inhibitors.

Drug Interactions

Ertugliflozin may enhance the hypoglycemic effect of insulin and insulin secretagogues; dose reduction of these medications may be necessary. Diuretics may have additive diuretic effects, increasing the risk of volume depletion. Ertugliflozin does not significantly inhibit or induce CYP450 enzymes and is unlikely to have metabolic drug interactions. UGT1A9 inducers (rifampin, phenytoin) may decrease ertugliflozin exposure; consider switching to an alternative SGLT2 inhibitor.

Special Populations

Ertugliflozin may cause fetal harm based on animal data showing adverse renal effects during organogenesis. It is not recommended during the second and third trimesters. It is unknown whether ertugliflozin is excreted in human breast milk; breastfeeding is not recommended. Safety and efficacy have not been established in pediatric patients. Elderly patients may be at increased risk for volume depletion-related adverse reactions. Dose initiation is not recommended when eGFR is less than 30 mL/min/1.73 m² due to reduced efficacy. No dose adjustment is needed for hepatic impairment.