番茄社区

SAN DIEGO -- The investigational SGLT-2 inhibitor ertugliflozin improved glycemic control in adults with type 2 diabetes, according to researchers here.

In the VERTIS clinical developmental program including five study arms, 5 mg and 15 mg daily of ertugliflozin was shown to significantly reduce HbA1c levels in addition to metformin, or when paired with initial administration in conjunction with sitagliptin.

VERTIS MET -- one of the two phase III VERTIS trials -- reported 5 mg of ertugliflozin after 26 weeks was able to significantly reduce A1c when compared with placebo (-0.70, 95% CI -0.87 to -0.53, P<0.001). Similarly, 15 mg of the drug also significantly reduced A1c after 26 weeks versus placebo (-0.88, 95% CI -10.5 to -0.71, P<0.001), according to Julio Rosenstock, MD, of the Dallas Diabetes and Endocrine Center, and colleagues, at the American Diabetes Association meeting.

After 26 weeks of treatment, a significantly greater percentage of patients in the 5-mg treatment group (35% versus 16%, P<0.001), as well as the 15-mg treatment group (40% versus 16%. P<0.001) achieved an A1c below 7% when compared with baseline measures.

The 5-mg ertugliflozin treatment group also reported improvements in fasting plasma glucose (FPG) levels from baseline to 26 weeks (-26.69, 95% CI -32.90 to -20.48, P<0.001) and body weight (-1.67, 95% CI -2.24 to -1.11, P<0.001), as well as systolic (-3.68, 95% CI -5.96 to -1.39, P=0.002) and diastolic blood pressure (-1.82, 95% CI -3.24 to 00.39. P=0.013).

Compared with baseline, 15 mg of the investigational agent also led to improvements for the same measures:

• FPG: -38.25 (95% CI -44.50 to -31.99, P<0.001)
• Body weight: -1.60 (95% CI -2.16 to -1.03, P<0.001)
• Systolic blood pressure: -4.50 (95% CI -6.81 to -2.19, P<0.001)
• Diastolic blood pressure: -2.42 (95% CI -3.86 to -0.98, P=0.001)

"These 'extra glycemic' effects are very important, as patients with type 2 diabetes are generally overweight or obese, and also have hypertension," noted Juan Frias, MD, of the National Research Institute in Los Angeles. Frias is a VERTIS MET investigator as well as a investigator.

"The medication was well tolerated, with an increased risk of genitourinary infections that are generally mild in nature, and seen with other medications in this class," Frias told 番茄社区. "As with other medications in this class, eventually having ertugliflozin available for clinical use will offer another alternative for [diabetic] patients not controlled with diet and exercise, or on single or combination anti-diabetic agents."

This arm of the trial program included 621 patients with type 2 diabetes, with baseline A1c between 7.0% to 10.5%. All participants were on 1,500 mg per day or greater of metformin monotherapy for 8 weeks or longer prior to the study. The MET arm included a 1:18:1 randomization, and Rosenstock's group aimed to assess the efficacy of ertugliflozin when combined with metformin, and to evaluate it's safety profile.

Adverse events reported were largely in line with events reported with other SGLT-2 inhibitors, including genital mycotic infection, which was higher among females in the 5- and 15-mg treatment group (5.5% and 6.3%, respectively) compared with placebo (0.9%, P=0.032). Males also reported a higher incidence of GMI with treatment (3.1% with 5 mg, 3.2% with 15 mg, and 0% with placebo. Urinary tract infection was also higher among those on ertugliflozin (2.9% with 5 mg, 3.4% with 15 mg, and 1.0% with placebo).

"Ertugliflozin is being assessed in these studies as monotherapy and also as add-on therapy to other anti-diabetic agents, generally versus placebo. The VERTIS trials also include a long-term cardiovascular outcomes trial which is ongoing, but has been fully enrolled," Frias stated.

In March 2017, the FDA and the European Medicines Agency accepted marketing applications for three type 2 diabetes treatments with ertugliflozin, based on the VERTIS program. These treatments included combination sitagliptin (Januvia) plus ertugliflozin, fixed-dose combo ertugliflozin with metformin, and monotherapy.

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