STOCKHOLM – Once-weekly treatment with the investigational, oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin lowered hemoglobin A1c as effectively as daily sitagliptin in a large, head-to-head, phase III trial of patients with type 2 diabetes.
Results of the O-QWEST noninferiority to sitagliptin study showed similar reductions in HbA1c from baseline to week 24 of treatment comparing omarigliptin (–0.47%) and sitagliptin (–0.43%) with an overall difference of just –0.03% (P = 0.561). The mean HbA1c at baseline in both groups was around 7.5%.
Patients with higher HbA1c values at baseline achieved greater reductions in HbA1c than those with lower starting HbA1c values, although there was no significant difference between the two treatments.
A similar percentage of patients in the omarigliptin and sitagliptin groups achieved target HbA1c values of less than 7% (54.4% vs. 52.4%; P = .619) and less than 6.5% (28.8% vs. 24.4%; P = .212), and there was no significant difference in fasting plasma glucose levels, with a mean difference overall of –0.2 mmol/L.
“According to a relatively recent joint position statement by the ADA and EASD (Diabetes Care. 2012;35:1364-1379) providing care that is responsive to individual patient preferences and needs is a recommended approach to health care in chronic diseases such as type 2 diabetes,” said Dr. Ira Gantz, who presented the study findings.
“Providing patients with medications tailored to their individual preferences and needs is consistent with this patient-centered approach, and the convenience of an effective, well-tolerated, weekly, oral, DPP-4 inhibitor may be an attractive option for some patients,” added Dr. Gantz, who is an employee of Merck & Co.
While an oral drug that is delivered weekly might prove more convenient and potentially improve patients’ adherence and quality of life, this was not possible to measure in the present study, Dr. Gantz noted during the discussion that followed his presentation of the results at the annual meeting of the European Association for the Study of Diabetes.
“The design of the study and of our other phase III programs makes that difficult because they’re double dummy, and the patients in this study who were taking omarigliptin also took daily sitagliptin [or placebo pill] and vice versa – those taking sitagliptin took a weekly placebo pill,” Dr. Gantz explained.
The global study compared the efficacy and safety of omarigliptin given at a once-weekly dose of 25 mg with that of sitagliptin (Januvia) at a daily dose of 100 mg in 642 patients with type 2 diabetes who were not achieving adequate glucose control despite being on metformin. The mean age of patients enrolled was around 57 years in both groups, with around half being male; the average duration of type 2 diabetes was 7 years.
Very small reductions in body weight were seen with both drugs but “no meaningful differences” in specific adverse events were seen, Dr. Gantz reported. Hypoglycemia developed in 3.7% of patients on the weekly regimen versus 4.7% in the subjects taking the daily DPP-4 inhibitor.
No confirmed cases of pancreatitis were reported in either treatment group. Two instances of angioedema, which was a prespecified hypersensitivity adverse event, of the tongue were noted in one subject in the omarigliptin group. There were some small increases in serum amylase and lipase in both groups although these were within normal laboratory limits and did not result in any treatment discontinuations.
Asked if there was any advantage of weekly over daily administration of a DPP-4 inhibitor in terms of renal function, Dr. Gantz replied that it might allow for “broader dose adjustment.” Patents with mild to moderate renal insufficiency would probably not need dose adjustment of omarigliptin, but for those with severe impairment and those on dialysis there would be a recommendation to halve the dose to 12.5 mg/week.
Dr. Gantz observed: “I think the major selling point is that it provides options for patients, as far as a weekly administration it’s a patient-centric approach.”
The study was funded by Merck & Co. Dr. Gantz and his coinvestigators are all employees of the company.