Adding rosiglitazone therapy to an insulin regimen appeared to be safe and to improve glycemic control in patients with type 2 diabetes in a study funded by the drug's manufacturer.
Rosiglitazone is one of the thiazolidinediones, “the newer insulin sensitizers” that improve β-cell function and prolong β-cell survival.
That result, in turn, enhances insulin sensitivity and improves glucose utilization, according to Dr. Ranjna Garg and associates at the Blackburn (England) Royal Infirmary's diabetes unit.
The first thiazolidinedione used in type 2 diabetes was troglitazone, a drug that was withdrawn from the market because of idiosyncratic reactions and sometimes fatal hepatic damage. Rosiglitazone has a different biochemical and metabolic profile and a lower incidence of hepatotoxicity, they said.
Dr. Garg and associates assessed its safety and efficacy in a 1-year open-label study of 53 patients who had inadequate glycemic control with insulin alone. The study was funded by GlaxoSmithKline.
Daily rosiglitazone reduced mean hemoglobin A1c by a statistically significant 1.53%, from an average of 9.82% to an average of 8.29%.
“Tight glycemic control with reduction in HbA1c by 1% is associated with reduction in diabetes-related end points by 21%, including death,” the investigators said (J. Diabetes Complications 2007;21:1–6).
The authors also noted, however, that the drug failed to reduce HbA1c to target levels recommended by the American Diabetes Association.
Mean reduction in total insulin dose was 13.5%, which was not statistically significant. Twenty-eight patients were able to reduce their insulin dosage, and the remaining 25 were not.
Mean blood pressure improved significantly when rosiglitazone was added to insulin therapy.
There was no clinical hepatotoxicity during 12-month follow-up. Four patients discontinued the drug because of weight gain and another four because they perceived no benefit from therapy. Rosiglitazone was withdrawn in one additional patient because of fluid retention.
In addition to funding this study, GlaxoSmithKline has funded the diabetes unit at Blackburn Royal Infirmary and provided a travel grant to Dr. Garg. Dr. Garg's associate in this study, Dr. Geraint Rhys Jones, has been on the company's advisory board.