Alogliptin, an investigational once-daily oral drug for type 2 diabetes, showed good efficacy and safety both as monotherapy and together with standard agents, researchers in five phase III trials stated at ADA Scientific Sessions.
Hemoglobin A1c levels declined 0.38 to 0.80 percentage points in type 2 diabetes patients given alogliptin, which has the same biological target as sitagliptin (Januvia), compared with changes of 0.19 points or less with placebo, according to reports at the American Diabetes Association meeting here.
Richard Pratley, M.D., of the University of Vermont, who helped conduct several of the trials, said the studies attempted to cover the spectrum of real-world clinical situations, "all the way from monotherapy in drug-naive patients to patients who need insulin."
Other drugs studied in combination with alogliptin included insulin, metformin, pioglitazone (Actos), and glyburide. The trials included a total of 2,504 patients with type 2 diabetes. Those with significant proteinuria (urinary albumin-creatinine ratio greater than 1 mg/mg) or a history of cancer were excluded.
Four of the studies — as monotherapy and in combination with metformin, pioglitazone, and glyburide — reported percentages of patients achieving HbA1c levels of 7% or below with six months of treatment. At a 12.5-mg daily dose versus placebo, results were:
Monotherapy: 47% versus 23% (P=0.001), With metformin: 52% versus 18% (P<0.001). With glyburide: 30% versus 18% (P=0.057), With pioglitazone: 44% versus 33% (P<0.03)
"It certainly has the efficacy required for approval and the drug is very well tolerated," Dr. Pratley said. He said there was "no evidence of weight gain" — a major drawback of thiazolidinedione agents — "no GI side effects, no skin issues with the drug, and very low rates of hypoglycemia."
About 15% to 18% of patients had significant hypoglycemic episodes across the trials, mostly with little or no difference compared with placebo, according to the reports.
Dr. Pratley said alogliptin appeared to contribute to extra instances of hypoglycemia when combined with glyburide, "but the increase is pretty minimal," he said. In the glyburide add-on study, about 11% of patients in the placebo arm had hypoglycemic events compared with 15% with alogliptin.
Like sitagliptin, alogliptin inhibits the dipeptidyl peptidase-4 enzyme, which degrades incretin hormones such as glucagon-like peptide-1. Sitagliptin is the only FDA-approved DPP-4 inhibitor. Novartis had applied for U.S. approval of a similar drug, vildagliptin (Galvus), but the FDA requested additional safety data in early 2007. Novartis said a resubmission is not expected before 2010. Vildagliptin is available in Europe.
"It’s hard to differentiate members of this class from one another," Dr. Pratley said. "They all tend to be very potent inhibitors of DPP-4. Efficacy is really determined more by the mechanism and the limitations of endogenous incretin secretion as opposed to the potency of the drug."
"All drugs inhibit DPP-4 100% and you expect them to have similar efficacy," he said. Although he acknowledged that alogliptin is essentially a me-too drug, he said it would still be valuable to have available.
"Patients need to have a choice, and providers and payers need to have a choice," Dr. Pratley said, suggesting that competition could reduce prices.
Alogliptin’s manufacturer, Takeda Pharmaceuticals, submitted an NDA for alogliptin to the FDA in January.
- Explain to interested patients that the investigational drug alogliptin appeared safe and effective in a variety of clinical situations.
- Point out the drug is not FDA-approved and is currently available only in a clinical trial setting.
American Diabetes Association meeting: Nauck M, et al "Efficacy and safety of alogliptin added to metformin therapy in patients with type 2 diabetes" ADA Meeting 2008; Abstract A142.
Pratley R, et al "Efficacy and safety of alogliptin added to pioglitazone therapy in patients with type 2 diabetes" ADA Meeting 2008; Abstract A143.
Fleck P, et al "Efficacy and safety of alogliptin monotherapy over 12 weeks in patients with type 2 diabetes" ADA Meeting 2008; Abstract 479.
Presented at the American Diabetes Association’s 68th Annual Scientific Sessions.
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