FDA Approves SGLT2 Inhibitor STEGLATRO, Fixed-Dose Combination STEGLUJAN

Merck announced the U.S. Food and Drug Administration (FDA) has approved STEGLATROTM (ertugliflozin) tablets, an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the fixed-dose combination STEGLUJAN (ertugliflozin and sitagliptin) tablets.

FDA Approves SGLT2 Inhibitor STEGLATRO, Fixed-Dose Combination STEGLUJAN

STEGLATRO is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. STEGLUJAN is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both ertugliflozin and sitagliptin is appropriate. STEGLATRO and STEGLUJAN are not recommended in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. STEGLUJAN has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using STEGLUJAN. STEGLATRO and STEGLUJAN are contraindicated in patients with severe renal impairment, end-stage renal disease or on dialysis, or with a history of a serious hypersensitivity reaction to ertugliflozin. STEGLUJAN is also contraindicated in patients with a history of a serious hypersensitivity reaction to sitagliptin (such as anaphylaxis or angioedema). Additional safety information can be found below.

These FDA approvals are supported by seven Phase 3 studies of approximately 4,800 patients. STEGLATRO was studied as monotherapy and in combination with metformin and/or sitagliptin, as well as with insulin and a sulfonylurea, in adults with type 2 diabetes and moderate renal impairment.

“In clinical trials, treatment with STEGLATRO resulted in significant A1C reductions when used alone or in combination with sitagliptin,” said Juan Pablo Frias, M.D., president and principal investigator, National Research Institute, Los Angeles. “This is important, as A1C-lowering is a key component of diabetes management, and many of my adult patients may need multiple medications to help manage their condition.”

Diabetes is a chronic, progressive disease affecting approximately 30 million Americans (90 to 95 percent have type 2 diabetes). About one-third of adults with type 2 diabetes in the U.S. are not at their A1C goal.

One of the studies supporting the FDA approvals was VERTIS SITA2, a 26-week double-blind, placebo-controlled study. VERTIS SITA2 evaluated STEGLATRO (ertugliflozin) compared to placebo in 463 patients with type 2 diabetes inadequately controlled (baseline A1C of 7.0-10.5%) on background metformin (≥1,500 mg/day) and sitagliptin (100 mg/day). Patients were randomized to STEGLATRO 5 mg, STEGLATRO 15 mg or placebo administered once daily, in addition to continuation of background metformin and sitagliptin therapy. In the study, STEGLATRO provided significant additional A1C reductions on top of metformin plus sitagliptin of 0.7 percent and 0.8 percent, respectively, for the 5 and 15 mg doses, compared with 0.2 percent for placebo (p<0.001, for both comparisons), which was the study’s primary endpoint.

In this study, STEGLATRO significantly reduced body weight by 6.6 pounds with the 5 mg dose and 6.2 pounds with the 15 mg dose, on top of metformin plus sitagliptin, compared with 2.2 pounds with placebo. Baseline body weight was 193.1 pounds, 190.9 pounds and 190.6 pounds for the 5 mg, 15 mg and placebo groups, respectively. The difference from placebo was -4.2 pounds for STEGLATRO 5 mg (95% CI: -5.7, -2.9) and -4.0 pounds for STEGLATRO 15 mg (95% CI: -5.3, -2.6). STEGLATRO 5 mg and 15 mg were also associated with significant reductions in fasting plasma glucose (25.7 mg/dL and 32.1 mg/dL, respectively, vs. 6.5 mg/dL for placebo; p<0.001, for both comparisons). Baseline fasting plasma glucose levels were 167.7 mg/dL, 171.7 mg/dL and 169.6 mg/dL for the 5 mg, 15 mg and placebo groups, respectively. Significant reductions in systolic blood pressure were also observed for STEGLATRO (3.8 mmHg for 5 mg and 4.5 mmHg for 15 mg, vs. 0.2 mmHg for placebo). Baseline systolic blood pressure values were 132.1 mmHg, 131.6 mmHg and 130.2 mmHg for the 5 mg, 15 mg and placebo groups, respectively. For systolic blood pressure, the difference from placebo was -3.7 mmHg for STEGLATRO (ertugliflozin) 5 mg (95% CI: -6.1, -1.2) and -4.3 mmHg for STEGLATRO 15 mg (95% CI: -6.7, -1.9). STEGLATRO is not indicated for weight loss or hypertension.

STEGLATRO causes intravascular volume contraction. Symptomatic hypotension may occur after initiating STEGLATRO, particularly in patients with impaired renal function (estimated glomerular filtration rate [eGFR] less than 60 mL/min/1.73 m2), elderly patients (≥65 years), patients with low systolic blood pressure or patients on diuretics. Before initiating STEGLATRO, volume status should be assessed and corrected if indicated.

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