This study evaluates the effectiveness and safety of tributyrin supplementation in patients with type 2 diabetes mellitus (T2DM) who are at increased risk of cardiovascular disease. Type 2 diabetes is commonly associated with poor blood sugar control, chronic inflammation, oxidative stress, and an increased risk of heart disease.

Tributyrin is a dietary supplement that acts as a precursor to butyrate, a compound known for its anti-inflammatory and metabolic benefits. It may help improve blood sugar levels, reduce inflammation, and lower cardiovascular risk.

In this randomized, double-blind, controlled clinical trial, participants will receive either tributyrin in addition to their standard diabetes treatment or standard therapy alone. The study will assess whether tributyrin improves glycemic control, inflammation, oxidative stress, lipid profile, and overall cardiovascular risk while maintaining safety and tolerability.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and progressive beta-cell dysfunction. It is strongly associated with chronic low-grade inflammation, oxidative stress, endothelial dysfunction, and an increased risk of atherosclerotic cardiovascular disease (ASCVD).

Short-chain fatty acids, particularly butyrate, have been shown to exert beneficial metabolic effects, including improving insulin sensitivity, reducing inflammation, and modulating oxidative stress. However, the clinical use of butyrate is limited by its poor bioavailability. Tributyrin, a triglyceride form of butyrate, serves as a prodrug that enhances absorption and provides sustained systemic release of butyrate.

Emerging evidence suggests that tributyrin may improve glycemic control, reduce inflammatory cytokines such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), enhance lipid metabolism, and improve endothelial function. Despite these promising findings, there is a lack of well-designed clinical trials evaluating its role in patients with T2DM, particularly those at elevated cardiovascular risk.

This study is a prospective, randomized, double-blind, controlled clinical trial conducted in adult patients with T2DM attending a diabetic outpatient clinic. Eligible participants will be randomly assigned in a 1:1 ratio to receive either oral tributyrin (500 mg twice daily) in addition to standard therapy or standard therapy alone for 12 weeks. Blinding will be maintained using identical capsules.

The primary objective is to evaluate the effect of tributyrin on glycemic control, assessed by fasting plasma glucose and glycated hemoglobin (HbA1c). Secondary objectives include assessment of inflammatory markers (CRP, IL-6, TNF-α), oxidative stress parameters (malondialdehyde and total antioxidant capacity), lipid profile (LDL-C, HDL-C, triglycerides), and estimated cardiovascular risk.

Safety outcomes will include monitoring of liver and renal function and the incidence of adverse events. Participants will be followed at regular intervals to assess treatment adherence, tolerability, and clinical response.

This study aims to determine whether tributyrin can serve as a safe and effective adjunctive therapy to improve metabolic control and reduce cardiovascular risk in patients with type 2 diabetes.

Inclusion Criteria:

• • Diagnosed with Type 2 DM for ≥ 1 year

  • ASCVD 10-year risk ≥ 7.5%
  • Stable antidiabetic and cardiovascular medication regimen for ≥ 3 months
  • Able to provide informed consent and comply with study procedures

Exclusion Criteria:

• • Established cardiovascular disease (history of MI, stroke, or revascularization)

  • Chronic gastrointestinal disorders affecting absorption
  • Severe hepatic or renal impairment
  • Use of GLP-1 receptor agonists or SGLT2 inhibitors
  • Pregnancy or lactation
  • Known hypersensitivity to tributyrin or butyrate