NEW YORK (Reuters Health) – When metformin and a sulphonylurea or a glinide fail to bring type 2 diabetes under control, adding pioglitazone may do the trick, French research suggests.

Furthermore, it’s better to make this move sooner rather than later, Dr. Guillaume Charpentier from Centre Hospitalier Sud Francilien, Corbeil Essonnes, and colleagues advise in the September issue of Diabetes, Obesity and Metabolism.

Their randomized double-blind placebo-controlled study involved 299 type 2 diabetic patients with hemoglobin A1C (HbA1C) levels 8% or greater despite dual therapy with metformin (1,700 mg/d or more) and a maximum dose of a sulphonylurea or a glinide.

Pioglitazone add-on therapy was started at 30 mg/d for 3 months and then either continued at that dose or titrated up to 45 mg/d if HbA1C was greater than 6.5% — as was the case in more than 90% of treatment arm subjects at 12 weeks.

The goal, according to the article, was to bring HbA1C levels down from baseline by at least 0.6% or to bring HbA1C below 7% at 7 months.

The minimum 0.6% reduction in HbA1C was achieved in 64.8% of treated patients and 9.5% of controls, the researchers report.

At 7 months, 39.4% of pioglitazone patients and 4.8% of placebo patients had HbA1C levels below 7%. Also, the authors note, HbA1C fell below 6.5% in 23% of treated patients and 2% of controls.

The proportion of patients who achieved the 7-month endpoint decreased as baseline HbA1C increased, the investigators noticed. In the pioglitazone arm, for example, a final A1C below 7% was reached by 44.4% of those with baseline levels below 8.5% versus 13% of those with baseline levels of 8.5% or higher.

Pioglitazone had other benefits as well. The homeostasis model assessment of insulin resistance (HOMA-IR), insulin, proinsulin and C-peptide decreased, and HOMA-B, which is a measure of basal beta-cell function, increased in the pioglitazone arm, relative to the placebo arm.

“Our results,” Dr. Charpentier and colleagues conclude, “highlight both the clinical consequences of delaying the decision to implement triple therapy for patients whose HbA1C continues to increase with dual metformin plus sulphonylurea therapy and the need to initiate early triple therapy with oral agents.”

The study was sponsored by Takeda France, from which Dr. Charpentier and another author have received travel, consultant and speakers’ fees.

Reference:
Diabetes Obesity Metab 2009;11:844-854.