The effects of nicotinamide and glimepiride on diabetes prevention in BB rats.

Glimepiride is an oral sulfonylurea drug; nicotinamide is an inhibitor of poly (ADP-ribose) synthetase and a precursor of NAD. Three studies were carried out to determine whether glimepiride and/or nicotinamide could prevent diabetes in BB rats. In Study I, we administered glimepiride treatment 200 mg/kg/day orally from the 35th to 143rd day of age. The incidence of diabetes in the glimepiride group was lower than in the control group (32% vs 55%, p < 0.02). In Study II, the treatment period was from the 35th to 147th day of age, and rats received glimepiride combined with nicotinamide (500 mg/kg/day IP). The treatment group showed a 22% incidence of diabetes compared to 53 in controls (p < 0.03). In Study III, nicotinamide treatment alone (1000 mg/kg/day orally) and combined with glimepiride were compared to untreated controls. The treatment period was from the 35th to 167th day of age. Nicotinamide-treated rats showed a 42% incidence of diabetes compared to 60% in controls (p = NS). In the nicotinamide combined with glimepiride treatment group, a lower incidence (28%) was observed when compared to the controls (60%, p < 0.05). These findings suggest that glimepiride can prevent diabetes in BB rats; however, nicotinamide when used in young animals shows only a trend to lower the incidence of diabetes, and when combined with glimepiride, no significant effect is observed.