Potential Role of Salicylates in Type 2 Diabetes

Abstract

Objective: To review the evidence base supporting the use of salicylates for glucose level control in patients with type 2 diabetes and provide a comprehensive review of available information describing the potential role of salicylates and, in particular, salsalate, for glucose control in type 2 diabetes prevention and treatment. DATA SOURCES: A literature search using MEDLINE (1966–March 2010), PubMed, and Google Scholar was conducted using the search terms salicylates, salicylic acid, aspirin, salsalate, acetytsalicylic acid, insulin, glucose, glycemic control, diabetes, hyperglycemia, and nuclear factor. The bibliographies of identified articles were reviewed for additional citations. Study Selection and Data Extraction: All relevant English-language information on the pharmacology, efficacy, and safety of salicylates for glucose control related to insulin resistance or diabetes prevention were reviewed. Preclinical data, clinical trials, and case reports were identified, evaluated, and included in this systematic review. Data Synthesis: Treatment of inflammation may be a potential novel strategy in prevention and treatment of type 2 diabetes, in which the body is resistant to the effects of insulin. Previous and recent studies reveal a possible relationship between inflammation and obesity. The chronic activation of the immune system due to low-grade inflammation was found in several studies to be associated with obesity, and this, in turn, can promote development of insulin resistance and impaired glucose tolerance. Administration of salicylates was shown over a century ago to lower glucose levels in patients with diabetes. Many in vitro and in vivo pharmacologic studies have demonstrated a glucose-lowering effect of salicylates. Salicylates, especially salsalate, were found in several clinical studies and case reports to be potential agents for diabetes treatment with a favorable safety profile. Although these studies had inherent limitations, such as small numbers of patients and short duration, the vast majority showed significant glucose-lowering effects. A large randomized trial, the National Institute of Diabetes and Digestive and Kidney Diseases–sponsored Targeting Inflammation with Salsalate in Type 2 Diabetes (TINSAL-T2D) trial, recently concluded that salsalate lowers hemoglobin A1c levels and improves glycemic control in patients with type 2 diabetes. Conclusions: Salicylates, especially salsalate, appear to be a promising treatment option for prevention or treatment of diabetes by lowering glucose levels. More extensive studies are needed to confirm the mechanisms involved and whether the effects are sustainable with continued administration of these agents. Further studies are warranted.