The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial.
BACKGROUND
Salsalate, a nonacetylated prodrug of salicylate, has been shown to decrease blood glucose concentration in small studies.


OBJECTIVE
To compare the efficacy and safety of salsalate at different doses in patients with type 2 diabetes.


METHODS
Parallel randomized trial with computer-generated randomization and centralized allocation. Patients and investigators, including those assessing outcomes and performing analyses, were masked to group assignment. (ClinicalTrials.gov registration number: NCT00392678)


METHODS
3 private practices and 14 universities in the United States.


METHODS
Persons aged 18 to 75 years with fasting plasma glucose concentrations of 12.5 mmol/L or less (< or = 225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% treated by diet, exercise, and oral medication at stable doses for at least 8 weeks.


METHODS
After a 4-week, single-masked run-in period, patients were randomly assigned to receive placebo or salsalate in dosages of 3.0, 3.5, or 4.0 g/d for 14 weeks (27 patients each) in addition to their current therapy.


METHODS
Change in HbA1c was the primary outcome. Adverse effects and changes in measures of coronary risk and renal function were secondary outcomes.


RESULTS
Higher proportions of patients in the 3 salsalate treatment groups experienced decreases in HbA1c levels of 0.5% or more from baseline (P = 0.009). Mean HbA1c changes were -0.36% (P = 0.02) at 3.0 g/d, -0.34% (P = 0.02) at 3.5 g/d, and -0.49% (P = 0.001) at 4.0 g/d compared with placebo. Other markers of glycemic control also improved in the 3 salsalate groups, as did circulating triglyceride and adiponectin concentrations. Mild hypoglycemia was more common with salsalate; documented events occurred only in patients taking sulfonylureas. Urine albumin concentrations increased in all salsalate groups compared with placebo. The drug was otherwise well tolerated.


CONCLUSIONS
The number of patients studied and the trial duration were insufficient to warrant recommending the use of salsalate for type 2 diabetes at this time.


CONCLUSIONS
Salsalate lowers HbA1c levels and improves other markers of glycemic control in patients with type 2 diabetes and may therefore provide a new avenue for treatment. Renal and cardiac safety of the drug require further evaluation.


BACKGROUND
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
Goldfine
Allison B
AB
Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Fonseca
Vivian
V
Jablonski
Kathleen A
KA
Pyle
Laura
L
Staten
Myrlene A
MA
Shoelson
Steven E
SE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000139:chemically induced; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage* / Q000009:adverse effects; D012459:Salicylates / Q000008:administration & dosage* / Q000009:adverse effects; D014012:Tinnitus / Q000139:chemically induced; D055815:Young Adult
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D011355:Prodrugs; D012459:Salicylates; C014182:salicylsalicylic acid