New Type 2 Diabetes Treatment Shows Promise in First Human Study

Mitchel L. Zoler, PhD, 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.

This is a summary of a preprint research study written by a team of researchers based at the Department of Nutrition and Movement Sciences at Maastricht University, The Netherlands, and their associates on Preprints with The Lancet, provided to you by Medscape. This study has not yet been peer-reviewed. The full text of the study can be found on SSRN First Look.

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