Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial

Ann Intern Med. 2013 Jul 2;159(1):1-12. doi: 10.7326/0003-4819-159-1-201307020-00003.

Abstract

Background: Short-duration studies show that salsalate improves glycemia in type 2 diabetes mellitus (T2DM).

Objective: To assess 1-year efficacy and safety of salsalate in T2DM.

Design: Placebo-controlled, parallel trial; computerized randomization and centralized allocation, with patients, providers, and researchers blinded to assignment. (ClinicalTrials.gov: NCT00799643).

Setting: 3 private practices and 18 academic centers in the United States.

Patients: Persons aged 18 to 75 years with fasting glucose levels of 12.5 mmol/L or less (≤225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% who were treated for diabetes.

Intervention: 286 participants were randomly assigned (between January 2009 and July 2011) to 48 weeks of placebo (n = 140) or salsalate, 3.5 g/d (n = 146), in addition to current therapies, and 283 participants were analyzed (placebo, n = 137; salsalate, n = 146).

Measurements: Change in hemoglobin A1c level (primary outcome) and safety and efficacy measures.

Results: The mean HbA1c level over 48 weeks was 0.37% lower in the salsalate group than in the placebo group (95% CI, -0.53% to -0.21%; P < 0.001). Glycemia improved despite more reductions in concomitant diabetes medications in salsalate recipients than in placebo recipients. Lower circulating leukocyte, neutrophil, and lymphocyte counts show the anti-inflammatory effects of salsalate. Adiponectin and hematocrit levels increased more and fasting glucose, uric acid, and triglyceride levels decreased with salsalate, but weight and low-density lipoprotein cholesterol levels also increased. Urinary albumin levels increased but reversed on discontinuation; estimated glomerular filtration rates were unchanged.

Limitation: Trial duration and number of patients studied were insufficient to determine long-term risk-benefit of salsalate in T2DM.

Conclusion: Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Kidney / drug effects
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Salicylates / administration & dosage*
  • Salicylates / adverse effects
  • Single-Blind Method
  • Young Adult

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Glucose
  • Glycated Hemoglobin A
  • Salicylates
  • salicylsalicylic acid

Associated data

  • ClinicalTrials.gov/NCT00799643