New FDA approval: daily SGLT-2 inhibitor for type 2 diabetes

Steglatro (ertugliflozin) is a sodium glucose co-transporter 2 inhibitor. SGLT-2 is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, ertugliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.

FDA

 

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FDA CENTER WATCH

DECEMBER 2017

 

General Information

Steglatro (ertugliflozin) is a sodium glucose co-transporter 2 (SGLT2) inhibitor.

Steglatro is specifically indicated as an adjunct to diet and exercise to improve glycemic control in adults with type II diabetes mellitus. Steglatro was also approved for use in combination with sitagliptin and in combination with metformin.

Steglatro is supplied as a tablet for oral administration. The recommended starting dose is 5 mg once daily, taken in the morning, with or without food. In patients tolerating 5 mg once daily, the dose may be increased to a maximum recommended dose of 15 mg once daily if additional glycemic control is needed. Please see drug label for administration in patients with renal impairment.

 

Clinical Results

The FDA approval of Steglatro was based on the following trials:

VERTIS Mono: a 26-week investigational study which evaluated ertugliflozin as monotherapy, met its primary endpoint, showing that patients randomized to ertugliflozin 5 mg and 15 mg had significantly greater A1C reductions of 0.99% and 1.16%, respectively, compared with placebo (p<0.001, for both comparisons). In addition, significantly more patients taking ertugliflozin 5 mg and 15 mg achieved the A1C treatment goal of <7.0% compared with placebo (p<0.001, for both comparisons), which was a secondary endpoint of the study.

VERTIS Factorial: a 26-week investigational study, evaluated the co-administration of ertugliflozin and Merck’s DPP-4 inhibitor Januvia (sitagliptin). This study also met its primary endpoint, with greater reductions in A1C observed in patients taking ertugliflozin in combination with sitagliptin compared to ertugliflozin or sitagliptin alone. An A1C reduction of 1.5% was observed in both combinations studied (ertugliflozin 5 mg or 15 mg with sitagliptin 100 mg), as compared with A1C reductions of 1.0% with ertugliflozin 5 mg alone, 1.1% with ertugliflozin 15 mg alone, and 1.1% with sitagliptin 100 mg alone.

VERTIS SITA2: in this double-blind, randomized, placebo-controlled study, 463 patients with type II diabetes and a baseline A1C of 7.0 - 10.5 percent were randomized to receive ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo. Both 5 mg and 15 mg daily doses of ertugliflozin showed significantly greater reductions in A1C of 0.69% and 0.76% , respectively, compared with placebo (p<0.001, for both comparisons), when added to patients on a background of sitagliptin (100 mg/day) and stable metformin (≥1500 mg/day).

In addition: a greater proportion of patients taking ertugliflozin 5 mg and 15 mg achieved the A1C treatment goal of < 7.0% compared with the placebo group (p<0.001, for both comparisons based on adjusted odds ratios); placebo-adjusted mean reduction in body weight of 4.4 lbs for the 5 mg dose and 3.7 lbs for the 15 mg dose (p<0.001, for both comparisons); pacebo-adjusted mean reductions in fasting plasma glucose (FPG) of 25.1 mg/dl for the 5 mg dose and 31.3 mg/dl for the 15 mg dose (p<0.001, for both comparisons) and placebo-adjusted mean reductions in systolic blood pressure of 2.9 mmHg (5 mg, p=0.019) and 3.9 mmHg (15 mg, p=0.002).

VERTIS MET: a 26-week study which evaluated the efficacy and safety of ertugliflozin in combination with metformin, compared with placebo and metformin, in adults with type 2 diabetes uncontrolled on metformin monotherapy. The study showed patients taking ertugliflozin 5 mg or 15 mg and metformin experienced greater reductions in A1C compared to placebo (0.7% and 0.9%, respectively, compared with 0.0% for placebo, p<0.001, for both comparisons).

Ertugliflozin in combination with metformin also met a secondary endpoint in the study, as significantly more patients taking either ertugliflozin 5 mg or 15 mg achieved the ADA’s recommended A1C treatment goal < 7.0% compared with placebo and metformin. As add-on therapy to metformin, treatment with ertugliflozin also resulted in significant reductions in fasting plasma glucose (FPG), body weight (BW), systolic blood pressure (SBP) and diastolic blood pressure (DBP), compared with placebo.

 

Side Effects

The most common adverse effect associated with the use of Steglatro is female genital mycotic infections.

 

Mechanism of Action

Steglatro (ertugliflozin) is a sodium glucose co-transporter 2 (SGLT2) inhibitor. SGLT2 is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, ertugliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.