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Alogliptin: Latest DPP-IV in the clinician’s armamentarium for type 2 diabetes
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The newest DPP-IV inhibitor, alogliptin, was approved by the FDA on Jan. 25. It will be available alone, combined with metformin and combined with pioglitazone. The standard dose is 25 mg by mouth once daily, and in those with moderate and severe renal impairment, the dose should be reduced to 12.5 mg and 6.25 mg daily, respectively. There have been several monotherapy and combination therapy trials published using alogliptin, as well as some safety trials.
Seino et al compared alogliptin (Nesina, Takeda Pharmaceuticals) — 6.25 mg, 12.5 mg, 25 mg or 50 mg daily — with placebo and voglibose (Voglib, Mascot Health Series; an alpha-glucosidase inhibitor) in 480 Japanese patients with type 2 diabetes. Treatment lasted 12 weeks, although a long-term (40 week) phase continued after the study. After 12 weeks, the HbA1c reductions with all doses of alogliptin were significantly higher than those seen with placebo or voglibose. The alogliptin HbA1c reductions for the 6.25-mg, 12.5-mg, 25-mg and 50-mg groups were 0.51%, 0.7%, 0.76% and 0.82%, respectively. Mean fasting plasma glucose reductions for these four doses of alogliptin were 9.3 mg/dL, 14.6 mg/dL, 17.5 mg/dL and 22.6 mg/dL. Hypoglycemia was rare with alogliptin, and there was no significant effect on weight.
Alogliptin vs. monotherapy, combinations
Seino et al also conducted a combination therapy study in which they evaluated the addition of alogliptin (12.5 mg or 25 mg daily) to existing metformin vs. existing metformin monotherapy in 288 Japanese patients. After 12 weeks, HbA1c decreased by 0.54% and 0.64% in the alogliptin 12.5-mg and 25-mg groups. The HbA1c reduction with metformin monotherapy was 0.21%. Fasting glucose also decreased significantly more in the alogliptin-treated patients. Finally, there was no difference in adverse effects with the addition of alogliptin.
James R. Taylor
Another study by DeFronzo and colleagues compared alogliptin alone (12.5 mg or 25 mg) or combined with pioglitazone (15 mg, 30 mg or 45 mg) in patients already on metformin. This study involved more than 100 patients who were followed for 26 weeks. After the study, the addition of alogliptin (either dose) to pioglitazone (Actos, Takeda Pharmaceuticals) resulted in an additional HbA1c reduction of 0.5%. The addition of alogliptin also positively affected several markers of beta-cell function. Hypoglycemia also was lower in the groups assigned to alogliptin compared with those assigned to pioglitazone alone.
In another combination study, Rosenstock et al randomly assigned 655 patients to one of four treatment groups: alogliptin 25 mg daily; pioglitazone 30 mg daily; alogliptin 12.5 mg daily plus pioglitazone 30 mg daily; or alogliptin 25 mg daily plus pioglitazone 30 mg daily. After 26 weeks, HbA1c decreases in these four groups were 0.96%, 1.15%, 1.56% and 1.71%, respectively. Hypoglycemia was uncommon in all groups.
Safety, efficacy studies
Another study assessed the safety and efficacy of adding alogliptin vs. increasing pioglitazone doses in patients with uncontrolled type 2 diabetes on metformin and pioglitazone. Patients were assigned alogliptin 25 mg daily or had their pioglitazone dose increased to 45 mg. After 52 weeks, those in the alogliptin group had a mean HbA1c reduction of 0.7% vs. an HbA1c reduction of 0.29% in those who were titrated to pioglitazone 45 mg daily. Furthermore, more patients in the alogliptin group reached the HbA1c goal (33.2% vs. 21.3%; P<.001), had a greater reduction in fasting glucose (0.8 mmol/L vs. 0.2 mmol/L; P<.001) and had greater improvements in measures of beta-cell function. Hypoglycemia was higher in the alogliptin group (4.5% vs. 1.5%), although the authors did not feel this was a clinically significant difference.
Finally, Nauck et al evaluated the addition of alogliptin 12.5 mg, 25 mg or placebo to existing metformin therapy. After 26 weeks, the mean HbA1c reduction with addition of either dose of alogliptin was 0.6%, and fasting glucose decreased by 17 mg/dL. This was significantly better than the placebo group, which had a mean HbA1c reduction of 0.2%. Rates of hypoglycemia were comparable between all three groups.
Alogliptin offers clinicians another effective and safe DPP-IV inhibitor. No head-to-head trials with other DPP-IV inhibitors have been published to date, so it is difficult to say at this point whether alogliptin has any advantages or disadvantages to other agents in the class.