New Weekly DPP-4 Inhibitor Effective in Diabetics in Japan

Marlene Busko

September 29, 2014

VIENNA — A novel, once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor, omarigliptin (Merck), was as effective in lowering HbA1c levels as sitagliptin (Januvia, Merck) and had a favorable safety profile, in the first phase 3 study results presented for this drug, from patients with type 2 diabetes in Japan.

"Treatment [with omarigliptin] over 24 weeks resulted in statistically significant and clinically meaningful improvements in glycemic control and was generally well tolerated," said Ira Gantz, MD, from Merck Research Laboratories, Whitehouse Station, New Jersey, who presented the findings at the recent European Association for the Study of Diabetes 2014 Meeting.

"The convenience of an effective, well-tolerated oral antihyperglycemic agent has the potential to improve patient adherence, which might translate into better glycemic control and disease outcomes," he noted.

The study compared a 25-mg/week dose of omarigliptin vs the standard 50-mg/day starting sitagliptin dose in patients in Japan. An ongoing, global phase 3 study is comparing this same dose of omarigliptin vs 100-mg/day of sitagliptin, which is the dose more usually used in the United States and elsewhere.

"These initial data suggest that once-weekly DPP-4 inhibition may be as efficacious as daily DPP-4 inhibition," Peter D. Reaven, MD, director, Diabetes Research Program, Phoenix VA Health Care System, in Arizona, told Medscape Medical News when asked to comment.

Since "type 2 diabetes frequently requires multiple medications to achieve appropriate glucose control…options that reduce daily pill intake and ease compliance can be helpful," although how this specific drug affects compliance has not yet been tested, he noted.

"There is no reason to suspect that effects would be that different in a non-Japanese population, but this will of course need to be demonstrated," he added.

Potential Simpler Treatment

One of the challenges in treating a chronic disease such as diabetes is pill adherence, Dr. Gantz said. Omarigliptin is a potent, highly selective oral DPP-4 inhibitor with a pharmacologic profile that allows for once-weekly dosing.

This study aimed to assess the safety and efficacy of 24 weeks of omarigliptin vs sitagliptin in a population of Japanese subjects with type 2 diabetes and inadequate glycemic control.

The trial enrolled diabetic patients age 20 and older who were not taking an antihyperglycemic agent and had an HbA1c between 7% and 10% or were taking an oral antihyperglycemic agent and had an HbA1c between 6.5% and 9%.

The trial randomized 166 patients to weekly omarigliptin, 165 patients to daily sitagliptin, and 83 patients to placebo.

At baseline, the patients had a mean age of 60, and about 70% were male. They had a body mass index (BMI) of 25, typical of patients in Japan. On average, they had had diabetes for 8 years and had a fasting plasma glucose of 9 mmol/L and a 2-hour postmeal glucose level of 13.5 mmol/L.

The initial mean HbA1c levels of patients randomized to omarigliptin, sitagliptin, and placebo were 7.9%, 8.0%, and 8.1%, respectively.

After 24 weeks of treatment, patients who received omarigliptin had a significantly greater mean reduction in HbA1c from baseline, compared with patients on placebo: 0.66% vs 0.13% (P < .001).

Patients who took omarigliptin had a similar change in HbA1c from baseline compared with patients who received sitagliptin: -0.66% vs -0.65%.

Omarigliptin also significantly reduced 2-hour postmeal glucose and fasting plasma glucose compared with placebo.

"The major treatment effect was observed by week 12," Dr. Gantz noted.

A 24 weeks, 47% of patients receiving omarigliptin had an HbA1c below 7% and 10.2% of these patients had an HbA1c below 6.5%.

About half of patients taking omarigliptin or sitagliptin and two-thirds of patients taking placebo had 1 or more adverse events. About 4% of patients taking the DPP-4 inhibitors and 6% of patients taking a placebo had a drug-related adverse event.

There were no deaths or serious drug-related adverse events.

Omarigliptin was not associated with symptomatic or severe hypoglycemia or any appreciative change in weight (a gain of 0.04 kg at 24 weeks).

Merck is now conducting 10 phase 3 clinical trials with omarigliptin involving approximately 8000 patients with type 2 diabetes, according to a company statement.

The current study represents the first phase 3 data for this drug and will be a key part of filing for regulatory approval in Japan, which the company plans to do by the end of 2014.

The study authors are all employees of Merck. Dr. Reaven discloses that he received research funding from from NovoNordisk and AstraZeneca and is a consultant for Amgen.

European Association for the Study of Diabetes 2014. September 17, 2014; Vienna, Austria. Abstract 115

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