Open AccessUse of Salsalate to Target Inflammation in the Treatment of Insulin Resistance and Type 2 Diabetes
Author(s) -
Goldfine Allison B.,
Silver Robert,
Aldhahi Waleed,
Cai Dongsheng,
Tatro Elizabeth,
Lee Jongsoon,
Shoelson Steven E.
Publication year - 2008
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2008.00026.x
Subject(s) - medicine , insulin resistance , type 2 diabetes , diabetes mellitus , insulin , endocrinology , adiponectin , inflammation , placebo , glucose homeostasis , pharmacology , alternative medicine , pathology
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‐κB 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‐κB 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‐κB as a therapeutic approach in type 2 diabetes.