Mitchel L. Zoler, Ph.D., for Medscape
November 18, 2021
Key Takeaways
- Patients with type 2 diabetes who received daily treatment with sodium phenylbutyrate for 2 weeks had significant improvements in peripheral insulin sensitivity and glucose oxidation.
- The treatment appeared safe, with no reported adverse events.
Why This Matters
- The results show, for the first time in humans, that treatment with an agent that cuts levels of branched-chain amino acids by boosting their breakdown produces substantial beneficial effects on glucose metabolism in patients with type 2 diabetes.
- The findings are proof-of-concept that treatments that target branched-chain amino acids may be a new management strategy for patients with type 2 diabetes.
Study Design
- A single-center, randomized, double-blind, placebo-controlled, crossover study with 18 enrolled patients and 16 patients with evaluable results who were included in the analysis.
- Patients were an average of 66 years old and had been diagnosed with type 2 diabetes for an average of 1.5 years.
- On top of their background glucose-lowering medications, participants received 4.8 g/m2/day sodium phenylbutyrate or placebo divided into three doses per day for 2 weeks, followed by a 6-8 week washout period, and then 2 weeks on the alternative treatment.
Key Results
- The primary outcome was change from baseline in peripheral insulin sensitivity, measured by the insulin-stimulated glucose disposal rate.
- Peripheral insulin sensitivity improved after 2 weeks on sodium phenylbutyrate by a significant 27% compared with placebo (P = .0155).
- Sodium phenylbutyrate also significantly improved several secondary measures compared with placebo including carbohydrate-driven muscle mitochondrial oxidative capacity, whole-body insulin-stimulated carbohydrate oxidation, and reduced plasma levels of branched-chain fatty acids.
Limitations
- The 16 evaluable patients were skewed by sex, with three women and 13 men participating.
- The study focused on treatment effects in skeletal muscle and liver and did not assess adipose tissue.
- Background therapy was not uniform across all 16 participants.
Disclosures
- The study received no commercial funding.
- The authors had no disclosures.
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