Salsalate has no effect on insulin secretion but decreases insulin clearance: a randomized, placebo-controlled trial in subjects without diabetes

Diabetes Obes Metab. 2015 Jun;17(6):608-612. doi: 10.1111/dom.12450. Epub 2015 Mar 12.

Abstract

To elucidate whether increased insulin concentration after salsalate treatment (3 g/day for 7 days) is attributable to an increased insulin secretion rate (ISR) or to reduced metabolic clearance of endogenous insulin (MCI) during stepped glucose infusion (SGI). The analysis was performed in obese subjects who participated in a randomized double-blind, parallel, placebo-controlled clinical trial. A total of 27 participants (16 on salsalate, 11 on placebo) completed baseline and follow-up SGI. During SGI in the salsalate group, C-peptide concentrations were reduced by 11%, while plasma insulin concentrations were increased by 30%, corresponding to a 30% reduction in MCI (p < 0.0001). At molar increments of glucose, insulin concentrations were increased by 27% (p = 0.02), but ISR was unchanged. Salsalate did not alter insulin secretion, but lowered MCI, indicating that a reduction in insulin clearance is the principal mechanism for increased insulin levels after salsalate administration.

Keywords: C-peptide; insulin secretion; salicylates; salsalate; stepped hyperglycaemia.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Double-Blind Method
  • Female
  • Glucose / administration & dosage
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Obesity / blood*
  • Obesity / drug therapy
  • Salicylates / pharmacology*
  • Secretory Rate / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Glucose
  • C-Peptide
  • Insulin
  • Salicylates
  • Glucose
  • salicylsalicylic acid