Patients with poorly controlled type 2 diabetes assigned to combination SGLT2 inhibitor and DPP-IV inhibitor therapy for 6 months saw a marked improvement in glycemic control vs. similar patients assigned to placebo, according to published findings from the phase 3 VERTIS SITA trial.
During the double-blind, randomized controlled trial, researchers also found that patients assigned a combination of the DPP-IV sitagliptin (Januvia, Merck) and the SGLT2 inhibitor ertugliflozin (Steglatro, Merck) experienced reductions in fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure vs. patients in the placebo group.
“In VERTIS SITA, patients taking Steglatro in combination with Januvia experienced greater reductions in HbA1c compared with patients taking placebo alone,” Sam Engel, MD, associate vice president, Merck clinical research, cardiometabolic and women’s health, told Endocrine Today. “Furthermore, significantly more patients taking this combination achieved the HbA1c treatment goal of less than 7%.”
Researchers analyzed data from 291 patients with type 2 diabetes and HbA1c at least 8% (mean HbA1c, 8.9%; mean diabetes duration, 6.3 years; mean BMI, 32.2 kg/m²). At screening, 51.9% of participants were prescribed antihyperglycemic therapy and entered an 8-week washout period before entering the study. Researchers randomly assigned patients 1:1:1 to ertugliflozin 5 mg/sitagliptin 100 mg once daily, ertugliflozin 15 mg/sitagliptin 100 mg once daily, or daily placebo for 26 weeks. The primary efficacy endpoint was change in HbA1c from baseline to 26 weeks.
At 26 weeks, patients in both combination-therapy groups experienced a reduction in HbA1c compared with placebo. For the 5-mg/100 mg dose group, the least squares mean HbA1c change was –1.7% from baseline to week 26 (95% CI, –1.9 to –1.5). For the 15-mg/100 mg dose group, least mean squares HbA1c change was –1.6% (95% CI, –1.8 to –1.4). The least mean squares change in HbA1c for the placebo group was –0.4% (95% CI, –0.7 to –0.2). At 26 weeks, 31.3% and 35.7% of patients in the 5-mg/100mg and 15-mg/100 mg groups, respectively, had HbA1c 7% or less vs. 8.3% in the placebo group, according to researchers.
“This is important because about one-third of adults with type 2 diabetes in the U.S. are not at their HbA1c goal, and many adult patients may need multiple medications to help manage their condition,” Engel said.
The researchers also observed reductions in FPG, 2-hour postprandial glucose, body weight and systolic BP in both combination-therapy groups compared with placebo. The incidence of the prespecified adverse events of urinary tract infection, genital mycotic infection, symptomatic hypoglycemia and hypovolemia were low and similar across groups, according to researchers.
“In patients with [type 2 diabetes] who had inadequate glycemic control with diet and exercise alone, co-initiation of ertugliflozin and sitagliptin provided clinically meaningful improvements in glycemic control and reduced body weight and [systolic blood pressure] relative to placebo,” the researchers wrote. “Combination treatment was generally well tolerated, without a meaningful difference in symptomatic hypoglycemia, [urinary tract infections], hypovolemia or genital mycotic infections relative to placebo.”
In December, the FDA approved three new medicines containing ertugliflozin with the indication of improving glycemic control in adults with type 2 diabetes, according to the agency’s Center for Drug Evaluation and Research, including Steglatro (oral ertugliflozin) and the fixed-dose combinations Steglujan (ertugliflozin and sitagliptin) and Segluromet (ertugliflozin and metformin). The three formulations will be made available in early 2018, according to Merck and Pfizer. – by Regina Schaffer
For more information:
Sam Engel, MD, can be reached at Merck & Co. Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033; email: email@example.com.
Disclosures: The authors report no relevant financial disclosures.