有効性と安全性を評価するためにランダム化比較試験が米国で実施された。プレセボ比較で3.0, 3.5, or 4.0 g/d for 14 weeksサルサレートが現在の治療薬に追加し、第一のアウトカムは、HbA1cの変化を測定。平均0.36% (P = 0.02) at 3.0 g/d、0.34% (P = 0.02) at 3.5 g/d、0.49% (P = 0.001) at 4.0 g/d減少した。安全性は、軽度の低血糖が見られた。
The Effects of Salsalate on Glycemic Control in Patients With Type 2 Diabetes;A Randomized Trial
Ann Intern Med. 2010 Mar 16;152(6):346-57.
・作用機序は、””Because of salsalate’s anti-inflammatory effects, our results suggest that inflammation plays a role in the pathogenesis of type 2 diabetes and that anti-inflammatory therapy may be useful for treating diabetes”(Allison B. Goldfine, MD, of the Joslin Diabetes Center in Boston)
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.
Design: 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)
Setting: 3 private practices and 14 universities in the United States.
Patients: Persons aged 18 to 75 years with fasting plasma glucose concentrations of 12.5 mmol/L or less (?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.
Intervention: 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.
Measurements: 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.
Limitation: 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.
Conclusion: 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.
Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.