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Pioglitazone with Insulin Improves Glycemic Control

Apr 14, 2010

Pioglitazone and insulin together allow greater glycemic control, plus other advantages, in Type 2 diabetics, researchers have found….

Lead author Dr. Bernard Charbonnel stated that, “On pioglitazone combined with insulin, glycemic control was improved with a decrease in insulin doses and a simplification of the glucose-lowering regimen…. In the placebo group, the insulin regimen intensified and the insulin doses increased.”


The 1,760 patients in the study were a subset of the larger PROactive cohort. The primary goal of the original randomized trial was to compare the effects of long-term treatment with pioglitazone vs placebo on cardiovascular events in 5,238 Type 2 diabetics with a history of vascular disease.

For the exploratory analysis reported online March 17 in the Journal of Clinical Endocrinology & Metabolism, Dr. Charbonnel, of Centre Hospitalier Universitaire de Nantes, and colleagues studied data just on the patients who were already taking insulin when they enrolled in PROactive. Along with their existing glucose-lowering therapies, 864 of these patients took pioglitazone and 896 received placebo.

Follow-up for a mean of almost 3 years showed a rapid and sustained decrease in insulin dose with pioglitazone and a progressive increase with placebo.

For example, for patients taking two injections every day at baseline, the mean daily insulin dose changed over the course of the study from 48.2 to 41.6 U with pioglitazone and from 47.4 to 53.2 U with placebo. There was a similar pattern for patients taking 3 or more injections/day at baseline: a drop from 64.9 to 54.4 U/day with pioglitazone, vs an increase from 66.9 to 72.6 U/day with placebo.

By the end of the study, the mean insulin daily dose was 42 U with pioglitazone and 55 U with placebo (p < 0.0001). Nine percent of pioglitazone patients and 2% of the placebo group were able to stop taking insulin altogether.

Fewer pioglitazone patients required multiple injections or other oral agents at the end of the study, and this group also had a significantly greater drop in HbA1c (0.93% vs 0.45%; p < 0.0001). Correlated with the decline in HbA1c, however, was an increase in body weight. The pioglitazone group gained an average of 4.2-kg from baseline to the final visit, compared to a decrease of 0.1 in the placebo group. Most of the weight gain occurred in the first year, the authors say.

Rates of the primary study endpoint — cardiovascular events or death — and the secondary endpoint (a composite of death, nonfatal myocardial infarction, and stroke) were not statistically significant between the groups.

Rates of heart failure, edema, and hypoglycemia were higher with pioglitazone, but there were no significant between-group differences in rates of serious events.

Dr. Charbonnel also pointed out, “The most insulin-resistant patients (defined as poorly controlled Type 2 diabetes despite high doses of insulin) showed the greatest glycosylated hemoglobin decline by adding pioglitazone to insulin.”

“In the insulin-treated patients in PROactive, pioglitazone use resulted in simplified insulin regimens, lower doses of insulin and better glycemic control over time, with a similar cardiovascular and safety profile as in the whole study population,” the research team concludes.

J Clin Endocrinol Metab 2010.