The National Institutes of Health–sponsored TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) trials determine whether this generic and inexpensive drug is safe, tolerated, and efficacious in diabetes. Stage 1 was a dose-ranging study whereas stage 2 of TINSAL-T2D is a larger study to assess the magnitude and durability of glycemic efficacy over 1 year, tolerability, and an array of safety variables relevant to patients with diabetes.

This trial evaluated glycemic effects of salicylate compared with placebo as add-on therapy for patients with inadequately treated, established T2DM. Salicylate is one of the oldest drugs in clinical practice, with documented use of relevant plant extracts for treating pain and inflammation dating back at least 3500 years. Nevertheless, its medicinal properties and mechanisms of action remain incompletely understood. When salicylate is acetylated by chemists, it yields aspirin. However, pure salicylate lacks an acetyl group and, thus, must have a different mechanism of action. Salicylate has not been tested previously for efficacy and safety under what regulatory agencies now consider to be current standard practice in clinical trials.

To assess 1-year efficacy and safety of salsalate treatment in patients with Type 2 Diabetes Mellitus.

Primary Outcome Measures:

• The Primary Outcome for the TINSAL-T2D Study is Change in HbA1c Level From Baseline to Week 48 From Baseline, Compared Between Treatment Groups.

Secondary Outcome Measures:

• Change From Baseline in Fasting Glucose Over Time.
• Response Rates for Reduction in Fasting Glucose of ≥20 mg/dl, a Reduction in HbA1c of ≥0.5%, and a Reduction in HbA1c of ≥0.8%
• Change in Lipids (Low-density Lipoprotein Cholesterol [LDL-C], Non-high-density Lipoprotein Cholesterol [Non-HDL-C], Triglycerides [TG], Total Cholesterol [TC], High-density Lipoprotein Cholesterol [HDL C], TC/HDL-C Ratio, and LDL-C/HDL-C Ratio)
• Changes in WBC and Differential, High-sensitivity C Reactive Protein (hsCRP), Other Inflammatory Markers
• Response Rates for Exceeding Hyperglycemic Targets Between Active and Placebo Treated Groups; Need for Rescue Therapy; Need for Discontinuation of Study Medication
• Response Rates in Patients Initially Treated With Lifestyle Modification, Insulin Secretagogue, Metformin or Combination Therapy

Inclusion Criteria: Eligible adult patients between 18 and 75 who had hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% at screening; and were treated by lifestyle modification or with metformin, insulin secretagogue, or dipeptidyl peptidase-4 inhibitor, alone or in combination.

Exclusion Criteria: Participants younger than 18 or older than 75 years using insulin, thiazolidinediones, glucagon-like peptide-1 agonists, NSAIDs, warfarin, or uricosuric agents were not eligible.

Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted.