Investigational SGLT2 inhibitor meets primary endpoint as add-on therapy in phase III trial

Ertugliflozin, an investigational oral SGLT2 inhibitor for the treatment of patients with type 2 diabetes, met its primary endpoint in the VERTIS SITA2 phase 3 study. Both 5 mg and 15 mg daily doses of ertugliflozin showed significantly greater reductions in A1C of 0.69 percent and 0.76 percent, 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).
These study results were presented for the first time during an oral session today at the 52^nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Munich, Germany.

In this double-blind, randomised, placebo-controlled study, 463 patients with type 2 diabetes and a baseline A1C of 7.0 – 10.5 percent were randomised to receive ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo in a 1:1:1 ratio. In addition to meeting the primary endpoint of reducing A1C at 26 weeks, ertugliflozin also met the following key secondary endpoints in the study:

• A greater proportion of patients taking ertugliflozin 5 mg and 15 mg achieved the A1C treatment goal of less than 7.0 percent (32.1 percent and 39.9 percent, respectively) compared with the placebo group (17.0 percent) (p<0.001, for both comparisons based on adjusted odds ratios);
• Placebo-adjusted mean reduction in body weight of 4.4 lbs (2.0 kg) for the 5 mg dose and 3.7 lbs (1.7 kg) for the 15 mg dose (p<0.001, for both comparisons);
• Placebo-adjusted mean reductions in fasting plasma glucose (FPG) of 25.1 mg/dl (1.4 mmol/L) for the 5 mg dose and 31.3 mg/dl (1.7 mmol/L) for the 15 mg dose (p<0.001, for both comparisons);
• 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).

Overall adverse event (AE) rates were generally similar between ertugliflozin 5 mg (41.7 percent), ertugliflozin 15 mg (43.8 percent) and placebo (48.4 percent), with a similar rate of one or more serious AEs across all groups (4.5 percent for ertugliflozin 5 mg; 2.0 percent for ertugliflozin 15 mg; 3.3 percent for placebo). The rates of discontinuations due to AEs were low across all groups (3.2 percent for ertugliflozin 5 mg; 0.7 percent for ertugliflozin 15 mg; 0.7 percent for placebo).
In the study, a higher incidence of genital mycotic infections was observed in patients taking ertugliflozin 5 mg and ertugliflozin 15 mg (males: 4.9 percent and 3.7 percent, respectively, vs. no events for placebo; females: 8.0 percent and 12.7 percent, respectively, vs. 1.9 percent for placebo). Urinary tract infection rates were low across the ertugliflozin 5 mg, ertugliflozin 15 mg and placebo groups (2.6 percent, 4.6 percent and 2.0 percent, respectively).
Across groups, there were similar rates for symptomatic hypoglycemia (3.8 percent for ertugliflozin 5 mg; 0.7 percent for ertugliflozin 15 mg; 2.6 percent for placebo) and for hypovolemia adverse events (0.6 percent for ertugliflozin 5 mg; no events for ertugliflozin 15 mg; 0.7 percent for placebo).

Source
Press release Pfizer and Merck, September 15, 2016