The present study has been carried out to investigate the relative potency of protease inhibitors (indinavir, ritonavir and atazanavir) on glucose-insulin homeostasis, hemoglobin and glycosylated hemoglobin in normal rats following oral administration for a period of 30 days. The effects of protease inhibitors were compared with normal control rats. Blood samples were collected from retro orbital puncture and the parameters observed are blood glucose, insulin, total hemoglobin, glycosylated hemoglobin and body weight. The insulin resistance index and percent beta cell function were determined by homeostasis model assessment (HOMA-1 and HOMA-2) models. Percent insulin sensitivity was determined by HOMA-2 model. Indinavir and ritonavir were significantly (p<0.05) elevated the blood glucose, insulin, insulin resistance index and glycosylated hemoglobin values and decreased the total hemoglobin, beta cell function, insulin sensitivity and body weights when compared to control rats. The alterations associated with indinavir are more compared to ritonavir treated rats. Atazanavir has not shown any significant effect on any parameter when compared to control rats, except increase in body weight. From this study we conclude that glucose-insulin homeostasis disorders associated with protease inhibitors are not a class specific, but are drug specific. Thus, it can be concluded that atazanavir is having safe profile compared to indinavir and ritonavir with respect to glucose-insulin homeostasis. Indinavir and ritonavir are having potent tendency to alter the glucose homeostasis and insulin profile to produce the events related to type 2 diabetes. So care should be taken when the indinavir and ritonavir are prescribed for their clinical benefit in diabetic patients.
