Approximately 7 million people in Japan have type 2 diabetes mellitus (T2DM). Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently not FDA approved; it is used in many other countries, such as Japan, India and Europe, as a dual oral agent with metformin or thiazolidinediones. In some countries, vildagliptin is used in combination with metformin and a sulfonylurea. Vildagliptin is currently dosed 50 mg orally, twice daily in approved countries; doses greater than 100 mg orally are not recommended. For patients with moderate to severe renal impairment, 50 mg orally once daily is recommended. Some common adverse effects of vildagliptin include dizziness, headache, and nasopharyngitis.
Previous studies have been successful in demonstrating the effects of other agents in combination with metformin. Currently there are 11 combination therapies with metformin. One of the newest metformin combinations is Xigduo® which is a combination of metformin and dapagliflozin. In January of this year, the FDA rejected a metformin/canagliflozin combination until more information becomes available. Almost all of the latest approved oral anti-diabetic agents are studied with or compared to metformin therapy.
This was a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm study comparing vildagliptin with placebo in T2DM patients who were previously taking metformin. All patients were inadequately controlled on metformin monotherapy at doses of 250 mg or 500 mg twice daily for at least 10 weeks prior to randomization. The patients who received vildagliptin received 50 mg twice daily in addition to their current metformin regimen. The study was conducted across 20 centers in Japan; a total of 136 patients were included in this study. Ages of the participants ranged from 20 to 75 years with BMIs between 20 to 35 kg/m2 and hemoglobin A1c (HbA1c) levels greater than 7.0% but less than 10.0%.
After 12 weeks of treatment, the participants were re-evaluated and HbA1c levels were analyzed. The vildagliptin group had a mean decrease in HbA1c of 1.1% from baseline. The placebo group had a mean decrease in HbA1c of 0.1% from baseline. The same results for change in HbA1c were present in both groups of metformin; patients taking 250 mg or 500 mg twice daily. Many patients in the vildagliptin groups achieved a target HbA1c of less than 7.0%; 64.1% of the subjects were less than 7.0% HbA1c and 30.9% were less than 6.5% HbA1c. The baseline HbA1c for both groups was 8.0% HbA1c. Both the placebo-controlled and vildagliptin group had similar incidences of adverse events (41.4% and 44.1%, respectively). A notable outcome was that there were no deaths or reports of hypoglycemia.
Odawara M, Hamada I, and Suzuki M. Efficacy and Safety of Vildagliptin as Add-on to Metformin in Japanese Patients with Type 2 Diabetes Mellitus. Diabetes Therapy. 2014 Mar. Doi:10.1007/s13300-014-0059-x.