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Pioglitazone may improve glycemic control in insulin-resistant HCV patients

Insulin-resistant patients with HCV experienced an improvement to indices of glycemic control, but not virologic response to treatment, with the addition of pioglitazone to standard care in a recent study.

Researchers randomly assigned insulin-resistant patients with HCV genotype 1 to receive either pegylated interferon alfa-2a (PEG-IFN a-2a) with ribavirin (standard care) (n=76) or 30 mg to 45 mg/day of oral pioglitazone in addition to standard care (n=79). Patients receiving pioglitazone underwent a 16-week run-in phase with the drug alone, 48 weeks receiving pioglitazone and standard care and an additional 24 weeks of pioglitazone alone. Standard care patients received 48 weeks of treatment followed by 24 weeks of untreated follow-up. Serum HCV RNA levels were collected at baseline and at 12, 24 and 48 weeks.

During run-in, the pioglitazone group experienced improvements to levels of HbA1c, plasma glucose, serum adiponectin and insulin, as well as insulin resistance score. Patients receiving standard care had similar improvements, but the effect was greater in the pioglitazone group for all factors excluding HbA1c.

After 12 weeks of standard care treatment, the change to mean HCV RNA was not significantly different between the two groups (–3.5 ± 1.71 IU/mL for pioglitazone compared with –3.7 ± 1.62 IU/mL for standard care, P=.4394). Sustained virological response was achieved by 26.0% of those in the pioglitazone group and 38.4% of the standard care group (P=.1021), with relapse occurring in 15.6% and 19.2% of patients, respectively (P=.5615).

Commonly reported adverse events included fatigue, anemia, nausea, headache and depression, with only incidence of depression significantly different between the groups (12% in pioglitazone group vs. 31% in standard care, P=.0051). Serious events were experienced by 13% of the pioglitazone group and 12% of the standard care group (P=1).

“Our study clearly demonstrates that improvement in insulin resistance with pioglitazone before, during and after 48 weeks of treatment with [PEG-IFN a-2a] plus ribavirin is not accompanied by an improved virologic response among patients infected with HCV genotype 1 with underlying insulin resistance,” the researchers concluded.

Disclosure: See the study for a full list of relevant disclosures.