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, firstname.lastname@example.org). 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, email@example.com.
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.
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Goldfine AB, Fonseca V, Jablonski KA, Chen YI, Tipton L, Staten MA, 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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