The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study

Juraj Koska, Erik Ortega, Joy C Bunt, Anna Gasser, Robert Hanson, John Forbes, Barbora de Courten, Jonathan Krakoff

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Abstract

Aim/hypothesis Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. Methods The study was a randomised, double-blind, placebocontrolled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI=30 kg/m2. The intervention was salsalate (3 g/day, n=28) or identical placebo (n=26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal (Rd) by euglycaemic?hyperinsulinaemic clamp (insulin infusion rate 40 mU m-2 min-1) and glucose tolerance by 75 g OGTT. Results The study was completed by 47 participants, of which 40 were analysed (salsalate n=22, placebo n=18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p=0.001) and glucose AUC during the OGTT (p=0.01), and in increased Rd (20 [8] vs 18 [6] ?mol [kg estimated metabolic body size]-1 min-1, p=0.002), while there was no significant change in these variables with placebo (p>0.3 for all). The effect of salsalate on Rd disappeared (p=0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p
Original languageEnglish
Pages (from-to)385 - 393
Number of pages9
JournalDiabetologia
Volume52
Issue number3
DOIs
Publication statusPublished - 2009

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