AMSTERDAM -- Patients with poorly controlled type 2 diabetes were four-times more likely to achieve target glycemia levels when metformin therapy was combined with a novel dipetidyl peptidase-4 (DPP-4) inhibitor, reported researchers here.
AMSTERDAM, Sept. 18 -- Patients with poorly controlled type 2 diabetes were four-times more likely to achieve target glycemia levels when metformin therapy was combined with a novel dipetidyl peptidase-4 (DPP-4) inhibitor, reported researchers here.
About one-third of patients given a combination of metformin and vildagliptin (Galvus) achieved a glycosylated hemoglobin (HbA1c) level of less than 7%, compared with 9.4% of patients given metformin and a placebo, said investigators at an industry sponsored symposium at the European Association for the Study of Diabetes meeting.
Among patients with HbA1c levels less than 8% at study outset, the combination of vidagliptin and metformin allowed 54%of them to achieve glycemic control, compared with 13.3% of patients in the control arm, said Martin Fitchet, M.D., of Novartis.
The drug is not approved for use in the U.S. Last February, the FDA asked Novartis to submit more data in order to obtain approval.
Vildagliptin is a member of a class of diabetes drugs called dipetidyl peptidase-4 (DPP-4) inhibitors. These agents are part of the broader class of incretin mimetics, which includes exenatide (Byetta), and sitagliptin (Januvia).
Incretin mimetics stimulate insulin secretion, protect beta cells, inhibit glucagon secretion, and help patients lose weight or remain weight neutral by delaying gastric emptying and inducing satiety.
"Overall, our clinical program has found continuous, sustained efficacy of at least 1% reductions in HbA1c, when the drug is either used alone or in combination therapy in patients who have either failed previous therapies or in the aggressive paradigm of dual combination therapy," Dr. Fitchet said.
Vildagliptin is also well tolerated in patients with mild renal impairment, and in elderly patients, without increasing the risk of hypoglycemia, he said.
The availability of new agents to treat type 2 diabetes is critically important in light of data showing that up to 40% of new users of oral antidiabetic agents fail to reach the HbA1c target of less than 7% in the first year of therapy, and about half of new users need to change therapy after a year, said Anthony Barnett, M.D., of the University of Birmingham in Birmingham, England.
Dr. Barnett said many patients require a change in therapy as soon as four months after initiating treatment. "We are dealing with a moving target: type 2 diabetes is a progressive disease that monotherapy often fails to control, and combination therapy or even triple therapy may fail to control glycemia long term, or even relatively short term," he said.
DPP-4 inhibitors address both the islet dysfunction and insulin resistance components of type 2 diabetes, said Johan-Baptist Gallwitz, M.D., of the University of Tubingen in Tubingen Germany.
"Insulin resistance is caused by genetic factors and by environmental factors," he said. "Islet dysfunction is actually the motor that drives the progression of the disease of type 2 diabetes.
Incretin mimetics have a glucose-dependent influence on beta-cell secretion of insulin, and also influence glucagons secretions, Dr. Gallwitz said.
Moreover, DPP-4 agents also address islet dysfunction through a mechanism of action that is complementary with oral agents such as metformin, pioglitazone (Actos), and rosiglitazone (Avandia), he said.
"DPP-4 inhibitors are the first new oral agents to use the incretin pathway, and they balance insulin and glucagon both," Dr. Gallwitz said. "Combination of vildagliptin and metformin provides a significant HbA1c reduction, including among those with very high baseline HbA1c levels."
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