Diabetes Add-On Treatments Vary in Kidney Care

Pioglitazone actions on reducing insulin resistance could mediate changes in renal function.

In a recent comparison between pioglitazone (Actos, Takeda Pharmaceuticals) and a basal insulin as adjunctive treatment for type 2 diabetes mellitus (DM), pioglitazone was associated with less deterioration of renal function.

"To the best of our knowledge, this was the first study to report that renal function may be better preserved by...pioglitazone [in] patients with type 2 DM in whom sulfonylurea and metformin control failed as compared with providing basal insulin therapy," said lead author Yu-Hung Chang, MD, Department of Internal Medicine, Lee's Endocrinology Clinic, Pingtung, Taiwan.

Chang (pictured) and colleagues noted that most studies evaluating add-on therapies are focused on the success in lowering HbA1c — the glycated hemoglobin measure of serum glucose fluctuation, and avoiding hypoglycemic events and body weight gain. "However, there has been less discussion of these anti-hyperglycemic agents in terms of the differences between them in preventing diabetes complications."

The researchers enrolled a total of 1,002 patients, with 559 receiving pioglitazone, 264 on insulin detemir (Levemir, Novo Nordisk), and 179 on insulin glargine (Lantus, Sanofi-Aventis). After propensity score matching, 105 patients remained in each group for comparative analysis. The metabolic and renal function changes in the patients were monitored over a mean 3.5 years.

Patients in all groups exhibited significant body weight gain, with greater increases in the pioglitazone and glargine groups than in the detemir group (2.1 and 1.6 kg vs 0.8kg). HbA1c was significantly improved in all groups, to a numerically greater degree in the pioglitazone group than with detemir or glargine.

The investigators staged the severity of chronic kidney disease (CKD) based on estimated glomerular filtration rate (eGFR) and albuminuria. They found the groups differed significantly in the measures of kidney function.

Those receiving detemir or glargine had a higher probability of developing or worsening CKD as compared to those receiving pioglitazone, with hazard ratios of 2.63 (95% confidence interval [CI] of 1.79-3.88) and 3.13 (95% CI 2.01-4.87), respectively. The percentage of CKD stage progress during the follow-up period in the pioglitazone group was 14%, compared to 26.4% with detemir and 23.4% with glargine.

"These results suggested that there may be a potential benefit of pioglitazone treatment in terms of renal function as compared with basal insulin," Chang and colleagues indicated.

The researchers suggest that the insulin resistance indicative of type 2 diabetes may have links to renal function change, and that the pioglitazone actions on reducing insulin resistance could mediate those changes.

The study, conducted without outside sponsors, was published in the May issue of Acta Diabetol.

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