Long-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trial

Gamma-amino butyric acid (GABA) has in experimental studies been found to promote beta-cell proliferation, enhance insulin secretion and reduce inflammation, positioning it as a candidate drug for type 1 diabetes (T1D) therapy. This phase I/II randomized controlled trial assessed the safety and efficacy of long-term treatment with Remygen^® (Diamyd Medical), a controlled-release oral GABA formulation, as a potential beta-cell regenerative therapy in adults with long-standing T1D. Thirty-five male subjects with T1D (≥ 5 years) were randomized into three arms receiving the study drug(s) once daily for 6 months: GABA 200 mg (Arm 1), GABA 600 mg (Arm 2) and GABA 600 mg + alprazolam 0.5 mg for 3 months followed by GABA 600 mg alone for 3 months (Arm 3). Safety measures, hormonal counter-regulation during hypoglycemic clamps, fasting- and stimulated C-peptide levels, were assessed at multiple timepoints. Safety concerns included elevated aspartate aminotransferase (AST) in nine subjects, leading to the withdrawal of two subjects. Most elevations were, however, transient with no dose-differences. No effects were observed on fasting- or stimulated C-peptide levels, CGM metrics or HbA1c. Hypoglycemic hormonal counter-regulation was unaltered. To conclude, we found no clinical evidence of a beta-cell regenerative effect of GABA, but side effects were commonly observed.