The Pharmaceutical Journal
Vol 277 No 7423 p476
21 October 2006

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Antidiabetic may lower side effects of other agents

Vildagliptin, an oral dipeptidyl peptidase-IV (DPP-IV) inhibitor in development for type 2 diabetes, has surprised investigators by showing it can attenuate side effects of other antidiabetic medicines when used in combination.

Data were discussed at the annual European Association for the Study of Diabetes meeting held in Copenhagen last month.

Vildagliptin works by boosting glucose-dependent incretin hormones, GLP-1 and GIP, produced in the gut after meals. Incretins stimulate both alpha and beta pancreatic islet cells so as to regulate glucagon-insulin balance in response to blood sugar changes. In type 2 diabetes, incretin response is diminished. DPP-IV inhibitors enhance incretin response by retarding breakdown of GLP-1 by the DPP-IV enzyme — a process normally effected within 90 seconds — in order to prolong its activity.

DPP-IV inhibitors are being studied as monotherapies and in combination with other antidiabetic drugs to improve poorly controlled diabetes.

Placebo-controlled vildagliptin combination-therapy studies, with metformin, with pioglitazone and with insulin, show it further reduces HbA_1c while attenuating rates of gastrointestinal disturbance, peripheral oedema and hypoglycaemic episodes, respectively.

In a double-blind, parallel-group, metformin study, 416 poorly controlled type 2 diabetes patients taking more than 1,500mg/day metformin were randomised to 24 weeks of either additional vildagliptin (50mg daily or twice daily) or placebo. The vildagliptin arms achieved further HbA_1c reductions of 0.7 per cent for 50mg daily and 1 per cent for 50mg twice daily (both P<0.001 versus placebo) and a three- to four-fold increase versus placebo in numbers achieving the greater than 7 per cent HbA_1c target. Fewer vildagliptin-treated patients experienced more than one gastrointestinal side effect (9.1 per cent and 14.8 per cent) than placebo-treated patients (18.2 per cent; P=0.02).

Alongside insulin in a 28-week double-blind, placebo-controlled extension study, 45 placebo-treated patients experienced 185 mild and six severe hypoglycaemic episodes, while 33 patients receiving added vildagliptin (50mg twice daily) experienced 118 mild and no severe hypoglycaemic episodes.

Vildaglitin is currently awaiting European and US regulatory approval.