Efficacy and safety of alogliptin added to sulfonylurea in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study

Yutaka Seino, Shinzo Hiroi, Masashi Hirayama, Kohei Kaku, Yutaka Seino, Shinzo Hiroi, Masashi Hirayama, Kohei Kaku

Abstract

Aims/introduction: To evaluate the efficacy and safety of alogliptin added to treatment with glimepiride.

Materials and methods: This multicenter, randomized, double-blind, parallel-group, 24-week (12-week observation and 12-week treatment) study compared alogliptin 12.5 or 25 mg in combination with glimepiride (1-4 mg/day) vs placebo added to glimepiride monotherapy in Japanese patients with type 2 diabetes who had poor glycemic control despite treatment with diet and exercise plus a sulfonylurea. The primary end-point was a change in glycated hemoglobin (HbA1c) from baseline. A 40-week open-label extension study evaluated the long-term safety and efficacy of the combination.

Results: Alogliptin 12.5 or 25 mg in combination with glimepiride significantly decreased HbA1c compared with glimepiride monotherapy after 12 weeks' treatment (-0.59, -0.65 and 0.35%, respectively; P < 0.0001 for both combination groups vs glimepiride monotherapy). Alogliptin 12.5 and 25 mg combination therapy was also associated with significantly higher responder rates (HbA1c <6.9%: 9.6% and 7.7%, HbA1c <7.4%: 29.8% and 34.6%) compared with glimepiride monotherapy (HbA1c <6.9%: 0%, HbA1c <7.4%: 3.9%). The incidence of adverse events was comparable between glimepiride monotherapy and alogliptin combination treatment, with most reported adverse events being mild in severity. In the extension study, the incidence of adverse events was comparable between the combination groups, with the majority of adverse events being mild.

Conclusions: Once-daily alogliptin was effective and generally well tolerated when given as add-on therapy to glimepiride in Japanese patients with type 2 diabetes who had inadequate glycemic control on sulfonylurea plus lifestyle measures. Clinical benefits were maintained for 52 weeks. This trial was registered with ClinicalTrials.gov (double-blind study no. NCT01318083; long-term study no. NCT01318135).

Keywords: Alogliptin; Glimepiride; Type 2 diabetes.

Figures

Figure 1
Figure 1
Disposition of patients in the 12‐week double‐blind study and 40‐week open‐label extension. AE, adverse event.
Figure 2
Figure 2
Changes in glycated hemoglobin (HbA 1c; mean and SD) at the completion of the double‐blind treatment period for glimepiride monotherapy, alogliptin 12.5 mg and alogliptin 25 mg groups in the full analysis set. ***P < 0.0001 vs placebo.
Figure 3
Figure 3
Time profiles of changes in glycated hemoglobin (HbA 1c; mean ± SD) in the alogliptin 12.5 and 25 mg groups during the course of the 52‐week clinical study (the period in which placebo was given is excluded).

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