Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes

Clin Transl Sci. 2008 May;1(1):36-43. doi: 10.1111/j.1752-8062.2008.00026.x.


Objectives: Chronic subacute inflammation is implicated in the pathogenesis of insulin resistance and type 2 diabetes. Salicylates were shown years ago to lower glucose and more recently to inhibit NF-kappaB activity. Salsalate, a prodrug form of salicylate, has seen extensive clinical use and has a favorable safety profile. We studied the efficacy of salsalate in reducing glycemia and insulin resistance and potential mechanisms of action to validate NF-kappaB as a potential pharmacologic target in diabetes.

Methods and results: In open label studies, both high (4.5 g/d) and standard (3.0 g/d) doses of salsalate reduced fasting and postchallenge glucose levels after 2 weeks of treatment. Salsalate increased glucose utilization during euglycemic hyperinsulinemic clamps, by approximately 50% and 15% at the high and standard doses, respectively, and insulin clearance was decreased. Dose-limiting tinnitus occurred only at the higher dose. In a third, double-masked, placebo-controlled trial, 1 month of salsalate at maximum tolerable dose (no tinnitus) improved fasting and postchallenge glucose levels. Circulating free fatty acids were reduced and adiponectin increased in all treated subjects.

Conclusions: These data demonstrate that salsalate improves in vivo glucose and lipid homeostasis, and support targeting of inflammation and NF-kappaB as a therapeutic approach in type 2 diabetes.

Keywords: adiponectin; glucose; inflammation; insulin resistance; salicylate; salsalate; type 2 diabetes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Blood Glucose / metabolism
  • Calorimetry / methods
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glucose Tolerance Test
  • Humans
  • Hyperglycemia / drug therapy
  • Hyperinsulinism / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Insulin / metabolism
  • Insulin Resistance*
  • Male
  • NF-kappa B / metabolism
  • Placebos
  • Salicylates / therapeutic use*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Glucose
  • Insulin
  • NF-kappa B
  • Placebos
  • Salicylates
  • salicylsalicylic acid