Salsalate improves glycaemia in overweight persons with diabetes risk factors of stable statin-treated cardiovascular disease: A 30-month randomized placebo-controlled trial.

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/m , 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 (P =0.018). Salsalate lowered total white blood cell counts (mean difference -0.7x10 /μL, 95%CI: -1.0 to -0.4 x10 /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.