Objective
To assess long‐term efficacy and safety of salsalate to improve glycemia in persons with diabetes risk, who are overweight with statin‐treated, stable coronary heart disease.
Methods
Glycemic status was assessed in 192 persons without diabetes at baseline in a pre‐specified secondary analysis from Targeting INflammation Using SALsalate in CardioVascular Disease (TINSAL‐CVD), a multi‐center, double‐masked, randomized (1:1), placebo‐controlled, parallel clinical trial.
Results
Participants were mostly Caucasian males, age 60±7 years, BMI 31.4±3.0 kg/m2, fasting glucose 92.8±11.0 mg/dL, and HbA1c 5.8±0.3%. Reductions in mean fasting glucose ‐5.70 mg/dL (95%CI: ‐7.44 to ‐3.97 mg/dL, P<0.001), HbA1c ‐0.11% (95%CI: ‐0.210 to ‐0.002%, P=0.046) and glycated serum protein ‐81.8 μg/mL (95%CI: ‐93.7 to ‐69.9 μg/mL, P<0.001) were demonstrated in salsalate compared to placebo‐assigned groups over 30 months. Reductions in fasting glucose and glycated serum protein were greater with salsalate compared to placebo in participants with prediabetes compared to a normoglycemic sub‐group (Pinteraction=0.018). Salsalate lowered total white blood cell counts (mean difference ‐0.7x103/μL, 95%CI: ‐1.0 to ‐0.4 x103/μL, P<0.001) and increased adiponectin (mean difference 1.8 μg/mL, 95%CI: 0.9 to 2.6 μg/mL, P<0.001) and albuminurea (16.7 μg/mg, 95%CI: 6.4 to 27.1 μg/mg, P<0.001) compared to placebo, consistent with previous results for patients with type 2 diabetes taking salsalate for shorter times.
Conclusions
Salsalate improves glycemia in obese persons at increased risk for diabetes, and hence may decrease risk of incident type 2 diabetes. Salsalate may inform new therapeutic approaches for diabetes prevention, but renal safety may limit clinical utility.