Oral monotherapy found effective, safe in elderly patients with type 2 diabetes

By Miriam E. Tucker

NATIONAL HARBOR, 18 dec 2008 – Monotherapy with the oral antihyperglycemic drug sitagliptin lowered blood glucose levels significantly, compared with placebo, and did not increase the risk for hypoglycemia in a study of 206 patients (aged 65-96 years) with type 2 diabetes. The study participants were inadequately controlled by dietary interventions and exercise alone.

The randomized, placebo-controlled, double-blind study was funded by Merck and Co., which manufactures sitagliptin under the name Januvia. Researchers from the Albert Einstein College of Medicine, New York, presented the results in a poster at the annual meeting of the Gerontological Society of America.

Of the 102 patients initially randomized to receive once-daily sitagliptin, 70 completed the 24-week treatment. Of the 104 randomized to placebo, 57 completed the study. The sitagliptin doses were 100 mg/day for people with normal kidney function and 50 mg/day for those with creatinine clearance rates of 30 mL/minute to 50 mL/minute.

Study participants had a mean age of 72 years and a mean baseline hemoglobin A_1c of 7.8%. In all, 53% were female. The two-thirds of patients who were using at least one antihyperglycemic medication prior to the study went through a washout period of 6-8 weeks prior to the study.

At 24 weeks, patients receiving sitagliptin had an average 0.5 percentage point reduction in HbA_1c from baseline, whereas patients in the placebo group had a 0.2 percentage point rise. More than twice as many patients who received sitagliptin reduced their HbA_1c levels to below 7.0%, with 35% of that group achieving that goal, compared with just 15% of the placebo group.

Patients with higher HbA_1c levels at baseline had greater improvements at 24 weeks, with a drop of 1.6 percentage points among those starting at 9.0% or above, 0.9 percentage points for those starting at 8.0%-9.0%, and 0.5 percentage points for those starting with an HbA_1c of less than 8.0%.

The 30 patients aged 75 years and older had similar HbA_1c responses to those of younger patients.

Reductions in mean 2-hour postmeal plasma glucose concentrations from baseline to week 24 were 61 mg/dL for the sitagliptin group and 27 mg/dL for the placebo group. Mean changes in body weight from baseline were losses of 1.1 kg for the sitagliptin group and 1.7 kg for participants receiving placebo, the researchers reported.

Drug-related adverse events occurred in 11% of the sitagliptin patients and in 9% of the placebo group. Abdominal pain, nausea, vomiting, and diarrhea occurred in 3% of sitagliptin patients and in 2% of placebo patients. Constipation occurred in 5% of the sitagliptin group and in none of the placebo patients.

The proportion of each group discontinuing the study because of any adverse event was 5% with sitagliptin and 3% with placebo. There were no reports of serious drug-related adverse events or of hypoglycemia in either group. Coronary artery disease was reported in 1% and 3% of the sitagliptin and placebo groups, respectively. There were no deaths in either group.

Dr. Nir Barzilai, an endocrinologist and director of the school’s Institute for Aging Research as well as a diabetes clinic at Montefiore Hospital in New York City, led the research team.

FDA Okays Broader Use for Sitagliptin (Januvia) in Type 2 Diabetes

WHITEHOUSE STATION, N.J., Oct. 18 -- Sitagliptin (Januvia), a DDP-4 inhibitor used in treatment of type 2 diabetes, has been approved for use in combination or add-on regimens, according to a release from the drug's manufacturer, Merck.
In October 2006, the FDA approved sitagliptin as an adjunct to diet and exercise to improve glycemic control in adults. The new labeling extends approval to permit use of sitagliptin in combination with metformin as initial therapy and as add-on therapy for patients who do not achieve glycemic control with sulfonylurea monotherapy or with the combination of sulfonylurea and metformin.
The drug maker said the FDA approved the expanded labeling after reviewing results of three studies that examined the efficacy of sitagliptin in combination regimens.
In addition to the expanded indications, the company said it will update the warnings and precautions on the label to include information about hypersensitivity based on post-marketing reports. The label will include a warning that the drug is contraindicated in patients with a history of serious hypersensitivity to sitagliptin, including anaphylaxis and angioedema.
Exfoliative skin conditions including Stevens-Johnson syndrome were also reported among patients taking the drug.
The recommended dose of sitagliptin is 100 mg once a day for all approved indications, except in patients with moderate or severe renal insufficiency or end-stage renal disease. For those with moderate insufficiency the recommended dose is 50 mg once a day and for those with severe insufficiency or ESRD, the dose is 25 mg once daily.