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

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/m 2 . 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 (R d ) by euglycaemic-hyperinsulinaemic clamp (insulin infusion rate 40 mU m −2 min −1) and glucose tolerance by 75 g OGTT. ResultsThe study was completed by 47 participants, of which 40 were analysed (salsalate n=22, placebo n=18

Skeletal muscle inflammation is not responsible for the rapid impairment in adiponectin response with high-fat feeding in rats

“…Additional conflicting results have been reported in humans following aspirin and salicylate derivative supplementation. Evidence of improved (10), unchanged (9,18,29), and decreased (2, 4, 13, 27) insulin sensitivity have all been reported following salicylate supplementation at doses (1-7 g/day in adult humans) and time periods (3 days to 4 wk), similar to the current study. In the current study, plasma ASA levels in supplemented animals averaged ϳ2 mM, consistent with previously reported levels in humans and animals (range 1-5 mM) and well below toxic levels (45,46).…”

Salsalate Activates Brown Adipose Tissue in Mice

“…Although some human studies (4,34) suggested that salsalate does not affect body weight, the effects on fat mass have not been reported. As mice have a relatively larger amounts of BAT compared with humans (35,36), activation of BAT by salsalate in humans might translate into improved fat distribution, and glucose and lipid metabolism without substantially affecting total body weight.…”

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

“…Salsalate, prodrug of salicylate, which unlike aspirin and sodium salicylate does not lead to bleeding risk, can improve insulin sensitivity and glucose control in prediabetic and T2DM patients with a good safety profile [74,75]. More particularly, a large randomized trial, the Targeting Inflammation with Salsalate in Type 2 Diabetes (TINSAL-T2D) trial, concluded that salsalate improves glucose control in T2DM patients with decrease in fasting glucose and glycated haemoglobin levels and enhances lipid profile [75].…”