New data show Novartis’ DPP-4 inhibitor Galvus is as good as Takeda’s Actos at reducing glycaemia in type 2 diabetes patients uncontrolled by high doses of standard metformin treatment, but unlike Actos it will not cause patients to gain weight.
The data from a 24-week randomised double-blind study conducted by Dr G. Bolli of University of Perugia have been submitted for publication to a diabetes and obesity journal but were presented during the European Association for the Study of Diabetes meeting in Amsterdam this week at a company satellite symposium.
Novartis Global Medical Director for Galvus (vildagliptin), Dr Martin Fitchett, said the study involved patients who had been uptitrated to at least 2g metformin daily but who still had inadequate glycaemic control with an HbA1c of at least 7.5% – above both the US target of 7 per cent and the European one of 6.5%. The trial randomised 295 patients to vildagliptin 100mg daily plus 2g or more of metformin, or to Actos (pioglitazone) 30mg daily plus metformin. Patients in both groups had a fasting plasma glucose (FPG) of 11mmol/L, a body mass index (BMI) of 32 and had been treated for diabetes for between six and seven years.
Results showed that after 24 weeks both drugs along with metformin reduced HbA1c by around a further 1% in patients with a baseline reading below 8.4% and by 1.5 per cent in patients whose baseline HbA1c was above 9%. “As expected most of pioglitazone’s effects were on FPG whilst Galvus’ effects on this were less marked. Most of the glycaemia-reducing effect with Galvus was driven by its action on prandial (mealtime) glucose levels,” he commented. The mean reduction in FPG was 1.4 mmol/l with vildagliptin plus metformin and 2.1 mmol/l with piofglitazone plus metformin.
No weight gain for vildagliptin patients
There was virtually no weight change in patients receiving vildagliptin 100mg (+0.3kg) but patients receiving pioglitazone 30mg daily gained an average 1.9 kg over six months if their BMI was below 35 at baseline, and 2.6kg if they were more obese at the start of the study.
“There was no real difference in the overall reporting of adverse events and in the low incidence of discontinuation,” he added. “This means that if a patient isn’t reaching their glycaemic target with metformin, they would do just as well by adding Galvus as a thiazolidinedione but they will not gain weight.” Patients are four times more likely to reach their target HbA1c if they receive both vildagliptin and metformin rather than metformin alone, he added.
Novartis is expecting to receive the go-ahead from European regulators to start marketing Galvus in the 27 countries of the EU, Iceland and Denmark very soon. The drug will be indicated in combination with metformin, a thiazolidinedione or with one of the sulphonylureas. The company received a positive opinion from the Committee for Medicinal Products for Human Use at the end of July; a time frame of up to 67 days is the usual interval before final approval.
The company had an approvable letter from the US Food and Drug Administration in February this year but was asked to provide further clinical trial data in patients with moderate to severe renal impairment. Trials have been designed and submitted for approval but Novartis has yet to receive the nod from the FDA to start conducting them. Data are unlikely to be available before 2009 at the earliest. By Olwen Glynn Owen