Available as tablets containing 5mg or 15mg ertugliflozin, Steglatro is licensed for use as an adjunct to diet and exercise: as monotherapy in patients for whom the use of metformin is considered inappropriate owing to intolerance or contraindications; or as combination therapy with other hypoglycaemic drugs, including insulin.
The efficacy and safety of ertugliflozin were assessed in seven key clinical studies involving 4,863 adults with type II diabetes, including a study of 468 patients with moderate renal impairment.
In a placebo-controlled monotherapy study (n=461) ertugliflozin provided effective glycaemic control in patients randomised to receive 5mg or 15mg of the SGLT2 inhibitor once daily. The placebo-adjusted least squares mean HbA1c changes from baseline to week 26 were -0.99% and -1.16%, respectively (p < 0.001 for both doses).
In addition, patients who received ertugliflozin were significantly more likely to achieve an HbA1c <7.0% than those who received placebo. Both doses of ertugliflozin were associated with significant reductions in fasting plasma glucose and two-hour post-prandial glucose levels and body weight.
Add-on therapy to metformin
In the VERTIS MET study (n=621) ertugliflozin 5mg or 15mg daily added to background metformin therapy (≥1.5g/day) produced significant reductions in HbA1c from baseline to week 26 (placebo-adjusted least squares mean -0.7% and-0.9%, respectively; p < 0.001 for both comparisons). Ertugliflozin was also associated with significant reductions in fasting plasma glucose, body weight and BP (systolic and diastolic) compared with placebo.
Ertugliflozin (5mg or 15mg daily) was compared with glimepiride (mean daily dose, 3mg) as add-on combination therapy with metformin (≥1.5g/day) in the 52-week VERTIS SU non-inferiority study (n=1,326).
At week 52, the least squares mean change (95% CI) from baseline in HbA1c was -0.6% (-0.7 to -0.5), -0.6% (-0.6 to -0.5) and -0.7% (-0.8 to -0.7) in the ertugliflozin 15mg, ertugliflozin 5mg and glimepiride groups, respectively, proving the study's primary hypothesis that ertugliflozin 15mg daily was non-inferior to glimepiride in reducing HbA1c (non-inferiority criterion: upper bound of the 95% CI about the treatment difference <0.3%).
Patients receiving ertugliflozin achieved greater body weight and systolic BP reductions than those receiving glimepiride.
Triple combination therapy
In the VERTIS FACTORIAL study (n=1,233) patients with inadequate glycaemic control on metformin (≥1.5g/day) were randomised to receive add-on therapy with once daily ertugliflozin 5mg or 15mg, sitagliptin 100mg, or to co-administration with ertugliflozin 5mg/sitagliptin 100mg or ertugliflozin 15mg/sitagliptin 100mg.
At week 26, least squares mean reductions in HbA1c were greater in the groups receiving combined add-on therapy (-1.5% for both) than in those receiving individual agents (-1.0%, -1.1% and -1.1% for ertugliflozin 5mg and 15mg and sitagliptin 100mg, respectively; p < 0.001 for all comparisons).
Body weight and systolic BP were also significantly reduced in the combination therapy groups compared with sitagliptin alone. Glycaemic control, body weight and BP effects of ertugliflozin were maintained to week 52.
In the VERTIS SITA2 study (n=464) the addition of ertugliflozin 5mg or 15mg daily to therapy in patients inadequately controlled on metformin (≥1.5g/day) plus sitagliptin (100mg daily) produced clinically meaningful and durable glycaemic control, body weight and systolic BP reductions versus placebo over 52 weeks.
Dual combination therapy
In the VERTIS SITA study (n=291) co-administration of ertugliflozin 5mg or 15mg plus sitagliptin 100mg daily in patients inadequately controlled by diet and exercise was shown to provide a clinically meaningful improvement in glycaemic control over 26 weeks.
Use in renal impairment
The VERTIS RENAL study (n=468) evaluated the safety and efficacy of ertugliflozin over 52 weeks in patients with type II diabetes and stage 3 chronic kidney disease. Reductions in blood glucose and body weight were observed with ertugliflozin and the drug was deemed by the study authors to have an acceptable safety profile in this patient population.
Ertugliflozin was generally well tolerated in clinical trials. The most commonly reported adverse effects were vulvovaginal mycotic infection and other female genital mycotic infections.