Over-the-counter analgesics normalize blood glucose and body composition in mice fed a high fat diet

Type 2 diabetes (noninsulin-dependent diabetes mellitus) develops from a pre-diabetic condition that is characterized by insulin resistance and glucose intolerance, and is exacerbated by obesity. In this study, we compared the ability of over-the-counter analgesic drugs (OTCAD) [acetaminophen (APAP); ibuprofen (IBU); naproxen (NAP); aspirin (ASA)], to protect against the development of a pre-diabetic state in mice fed a high fat diet. After 10 weeks on the high fat diet, mice had normal fasting blood glucose (FBG) levels, but exhibited impaired glucose tolerance. Treatment with 20 mg OTCADs/kg body weight improved glucose tolerance, with the order of efficacy, APAP = ASA > IBU, while NAP proved ineffective. Mice fed the high fat diet also exhibited increases in weight gain associated with an increase in body fat. OTCADs prevented in part this increase in body fat, in the order of efficacy, APAP = IBU > NAP = ASA. In isolated liver mitochondria, OTCADs inhibited succinate-dependent H2O2 production, while in white adipose tissue, APAP inhibited NADPH-oxidase mediated H2O2 production and lipid peroxidation. Thus, OTCADs diminish pro-oxidant processes that might otherwise exacerbate inflammation and a pre-diabetic state. We conclude that OTCADs, especially APAP and IBU, may be valuable tools to delay or prevent the development of type 2 diabetes from a pre-diabetic condition.