title: Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study.
abstract: OBJECTIVE
  Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance.
  
  
  METHODS
  This was a randomized (2:1), single-blind, placebo-controlled study of salsalate (3.5 g daily for 4 weeks) in nondiabetic individuals with insulin resistance. All individuals had measurement of glucose tolerance (75-g oral glucose tolerance test), steady-state plasma glucose (SSPG; insulin suppression test), and insulin secretion and clearance rate (graded-glucose infusion test) before and after treatment.
  
  
  RESULTS
  Forty-one individuals were randomized to salsalate (n = 27) and placebo (n = 14). One individual from each group discontinued the study. Salsalate improved fasting (% mean change -7% [95% CI -10 to -14] vs. 1% [-3 to 5], P = 0.005) but not postprandial glucose concentration compared with placebo. Salsalate also lowered fasting triglyceride concentration (-25% [-34 to -15] vs. -6% [-26 to 14], P = 0.04). Salsalate had no effect on SSPG concentration or insulin secretion rate but significantly decreased insulin clearance rate compared with placebo (-23% [-30 to -16] vs. 3% [-10 to 15], P < 0.001). Salsalate was well tolerated, but four individuals needed a dose reduction due to symptoms.
  
  
  CONCLUSIONS
  Salsalate treatment in nondiabetic, insulin-resistant individuals improved fasting, but not postprandial, glucose and triglyceride concentration. These improvements were associated with a decrease in insulin clearance rate without change in insulin action or insulin secretion.
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA sunhkim@stanford.edu.
authors: Sun H
authors: SH
authors: Kim
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Alice
authors: A
authors: Liu
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Danit
authors: D
authors: Ariel
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Fahim
authors: F
authors: Abbasi
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Cindy
authors: C
authors: Lamendola
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Kaylene
authors: K
authors: Grove
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Vanessa
authors: V
authors: Tomasso
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Hector
authors: H
authors: Ochoa
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Gerald
authors: G
authors: Reaven
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects; D012459:Salicylates / Q000494:pharmacology*; D016037:Single-Blind Method; D014280:Triglycerides / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D007328:Insulin; D012459:Salicylates; D014280:Triglycerides; C014182:salicylsalicylic acid