Allison B. Goldfine, MD; Vivian Fonseca, MD; Kathleen A. Jablonski, PhD; Yii-Der Ida Chen, PhD; Laura Tipton, MS; Myrlene A. Staten, MD; Steven E. Shoelson, MD, PhD; for the Targeting Inflammation Using Salsalate in Type 2 Diabetes Study Team*
Acknowledgment: The authors thank Elizabeth Tatro for her coordinating roles in the trial and Yeheng Liu, MPH, Cedars-Sinai Medical Center, for laboratory measurements.
Grant Support: By National Institutes of Health (U01 DK74556, P50 HL83813, P30 DK03836, and General Clinical Research Center and Clinical and Translational Science Award at several sites) and the Tullis-Tulane (Dr. Fonseca) and Helen and Morton Adler (Dr. Shoelson) Chairs. Caraco Pharmaceutical Laboratories (Detroit, Michigan) supplied the salsalate and placebo, LifeScan (Milpitas, California) supplied the home glucose-monitoring kits, and Mercodia (Uppsala, Sweden) supplied the insulin assay kits.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-2782.
Reproducible Research Statement: Study protocol: Available from Dr. Goldfine (e-mail, email@example.com). Data set and statistical code: Not available.
Requests for Single Reprints: Steven E. Shoelson, MD, PhD, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Goldfine and Shoelson: Joslin Diabetes Center, One Joslin Place, Boston, MA 02215.
Dr. Fonseca: Tulane University Health Sciences Center, Department of Medicine, Section of Endocrinology, 1430 Tulane Avenue, SL 53, New Orleans, LA 70112.
Dr. Jablonski and Ms. Tipton: The George Washington University, The Biostatistics Center, 6110 Executive Boulevard, Suite 750, Rockville, MD 20852.
Dr. Chen: Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048.
Dr. Staten: National Institute of Diabetes and Digestive and Kidney Diseases, Division of Diabetes, Endocrinology, and Metabolic Diseases, Building 2 DEM, Room 6107, 6707 Democracy Boulevard, Bethesda, MD 20892.
Author Contributions: Conception and design: A.B. Goldfine (conception), V. Fonseca, K.A. Jablonski, M.A. Staten, S.E. Shoelson (conception).
Analysis and interpretation of the data: A.B. Goldfine, V. Fonseca, K.A. Jablonski, Y.D.I. Chen, L. Tipton, M.A. Staten, S.E. Shoelson.
Drafting of the article: A.B. Goldfine, K.A. Jablonski, S.E. Shoelson.
Critical revision of the article for important intellectual content: A.B. Goldfine, V. Fonseca, K.A. Jablonski, M.A. Staten, S.E. Shoelson.
Final approval of the article: A.B. Goldfine, V. Fonseca, K.A. Jablonski, M.A. Staten, S.E. Shoelson.
Provision of study materials or patients: A.B. Goldfine.
Statistical expertise: K.A. Jablonski, L. Tipton.
Obtaining of funding: A.B. Goldfine, V. Fonseca, S.E. Shoelson.
Administrative, technical, or logistic support: A.B. Goldfine, V. Fonseca, K.A. Jablonski, Y.D.I. Chen, L. Tipton, M.A. Staten.
Collection and assembly of data: A.B. Goldfine, V. Fonseca, K.A. Jablonski, S.E. Shoelson.
Short-duration studies show that salsalate improves glycemia in type 2 diabetes mellitus (T2DM).
To assess 1-year efficacy and safety of salsalate in T2DM.
Placebo-controlled, parallel trial; computerized randomization and centralized allocation, with patients, providers, and researchers blinded to assignment. (ClinicalTrials.gov: NCT00799643)
3 private practices and 18 academic centers in the United States.
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.
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).
Change in hemoglobin A1c level (primary outcome) and safety and efficacy measures.
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.
Trial duration and number of patients studied were insufficient to determine long-term risk–benefit of salsalate in T2DM.
Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted.
National Institutes of Health.
Allison B. Goldfine, Vivian Fonseca, Kathleen A. Jablonski, Yii-Der Ida Chen, Laura Tipton, Myrlene A. Staten, et al. Salicylate (Salsalate) in Patients With Type 2 Diabetes: A Randomized Trial. Ann Intern Med. 2013;159:1–12. doi: 10.7326/0003-4819-159-1-201307020-00003
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Published: Ann Intern Med. 2013;159(1):1-12.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.
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