Coinitiation of ertugliflozin and sitagliptin in patients with type 2 diabetes with blood sugars inadequately managed with diet and exercise resulted in clinically meaningful improvement in glycemic control over 26 weeks, according to results published in Diabetes Therapy.1
To assess the efficacy and safety of coinitiation of ertugliflozin and sitagliptin compared with placebo in patients with type 2 diabetes with inadequately managed glycemic control, researchers conducted a phase 3, randomized, double-blind, multicenter, placebo-controlled, 26-week trial (Clinicaltrials.gov identifier: NCT02226003).
A total of 291 patients with measured hemoglobin A1c (HbA1c) values between 8.0% and 10.5% on diet and exercise were randomly assigned 1:1:1 to receiver either ertugliflozin 5 mg/day and sitagliptin 100 mg/day (E5/S100 group), ertugliflozin 15 mg/day and sitagliptin 100 mg/day (E15/S100 group), or placebo. The patients’ average HbA1c at baseline was 8.9%. The primary study end point was the change in HbA1c from baseline at week 26.
Overall, 254 patients (87.3%) completed the study; 90 (91.8%) completed the E5/S100 regimen, 88 (91.7%) the E15/S100 regimen, and 76 (78.4%) the placebo regimen.
At week 26, both treatment regimens with ertugliflozin and sitagliptin aided in significantly reducing HbA1c from baseline compared with placebo. The least squares mean HbA1c change (95% CI) from baseline was –1.7% (–1.9, –1.5) for E15/S100, –1.6% (–1.8, –1.4) for E5/S100, and –0.4% (–0.7, –0.2) for placebo.
At week 26, the percentage of patients who achieved an HbA1c of <7.0% was 31.3% in the E15/S100 group, 35.7% in the E5/S100 group, and 8.3% in the placebo group.
There were significant reductions in fasting plasma glucose, 2-hour post-prandial glucose, body weight, and systolic blood pressure in both of the ertugliflozin/sitagliptin groups compared with placebo.
Incidences of the pre-specified adverse events — urinary tract infection, genital mycotic infection, symptomatic hypoglycemia, and hypovolemia — were low and not meaningfully different across all groups.
In an email to Endocrinology Advisor, Sam Engel, MD, associate vice president of Merck Clinical Research, Cardiometabolic and Women’s Health, and VERTIS SITA study investigator, explained the benefits of the coinitiation of a sodium-glucose co-transporter 2 (SGLT) inhibitor with a dipeptidyl peptidase-4 (DPP-4) inhibitor in patients already taking metformin.
“About one-third of adults with type 2 diabetes in the US are not at their A1c goal, and many adult patients may need multiple medications to help manage their condition,” Dr Engel said. “In [the] VERTIS SITA [study], patients taking STEGLATRO [ertugliflozin] in combination with JANUVIA [sitagliptin] experienced greater reductions in A1C compared with patients taking placebo alone.”
Dr Engel also added that in VERTIS FACTORIAL, a study published online in Diabetes, Obesity and Metabolism in December 2017, 1233 patients with type 2 diabetes who were inadequately controlled on metformin alone (≥1500 mg/day) were examined,2 and “the co-administration of STEGLATRO [ertugliflozin] and JANUVIA [sitagliptin] was significantly more effective than either medication alone in achieving an A1C goal of less than 7.0 percent.”
In patients already taking metformin, Dr Engel also offered pointers to avoid the risk of hypoglycemia when initiating new medications.
“As noted in the ADA Standards of Care, it is important to individualize pharmacologic therapy to reduce the risk of hypoglycemia, particularly in older or hospitalized patients, and those prone to hypoglycemia,” he said. “The Standards of Care distinguish the classes of antihyperglycemic therapies that do not cause hypoglycemia from those that can cause hypoglycemia.3 DPP-4 inhibitors, such as sitagliptin, and SGLT2 inhibitors, such as ertugliflozin, could be useful choices in a strategy to avoid hypoglycemic risk.”
Limitations of the VERTIS SITA study included not directly comparing treatment with metformin, the recommended first-line therapy in most patients with type 2 diabetes. In addition, not all patients were drug-naive — approximately 50% of patients had discontinued prior therapy before the placebo run-in and study arm randomization.
The VERTIS SITA researchers concluded that in patients with type 2 diabetes who did not have adequate glycemic control with diet and exercise alone, “coinitiation of ertugliflozin and sitagliptin provided clinically meaningful improvements in glycemic control and reduced body weight and [systolic blood pressure] relative to placebo.”
The combination therapy was also generally well tolerated, with no meaningful difference in symptomatic hypoglycemia, urinary tract infections, hypovolemia, or genital mycotic infections compared with placebo.
Study Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, in collaboration with Pfizer Inc., provided financial support for this study.
Disclosures: Several study authors have ties to Merck & Co, Inc. and the pharmaceutical industry. Please refer to the original study for full disclosure information.
- Miller S, Krumins T, Zhou H, et al. Ertugliflozin and sitagliptin co-initiation in patients with type 2 diabetes: the VERTIS SITA randomized study [published online January 8, 2018]. Diabetes Ther. doi:10.1007/s13300-017-0358-0
- Pratley RE, Eldor R, Raji A, et al. Ertugliflozin plus sitagliptin versus either individual agent over 52 weeks in patients with type 2 diabetes mellitus inadequately controlled with metformin: the VERTIS FACTORIAL randomized trial [published online December 21, 2017]. Diabetes Obes Metab. doi:10.1111/dom.13194
- Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2018. Diabetes Care. 2018;41(Suppl 1):S73-S85.