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(2), 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 mu g/mL (95% CI:-93.7 to-69.9 mu g/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-interaction= 0.018). Salsalate lowered total white blood cell counts (mean difference -0.7x10(3)/mu L, 95% CI: -1.0 to -0.4x10(3)/mu L, P<0.001) and increased adiponectin (mean difference 1.8 mu g/mL, 95% CI: 0.9 to 2.6 mu g/mL, P<0.001) and albuminurea (16.7 mu g/mg, 95% CI: 6.4 to 27.1 mu g/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.