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Glucagon-like peptide-1 receptor agonists reverse nerve morphological abnormalities in diabetic peripheral neuropathy

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Abstract

Aims/hypothesis

Diabetic peripheral neuropathy (DPN) is a highly prevalent cause of physical disability. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes and animal studies have shown that glucagon-like peptide-1 (GLP-1) receptors are present in the central and peripheral nervous systems. This study investigated whether GLP-1 RAs can improve nerve structure.

Methods

Nerve structure was assessed using peripheral nerve ultrasonography and measurement of tibial nerve cross-sectional area, in conjunction with validated neuropathy symptom scores and nerve conduction studies. A total of 22 consecutively recruited participants with type 2 diabetes were assessed before and 1 month after commencing GLP-1 RA therapy (semaglutide or dulaglutide).

Results

There was a pathological increase in nerve size before treatment in 81.8% of the cohort (n=22). At 1 month of follow-up, there was an improvement in nerve size in 86% of participants (p<0.05), with 32% returning to normal nerve morphology. A 3 month follow-up study (n=14) demonstrated further improvement in nerve size in 93% of participants, accompanied by reduced severity of neuropathy (p<0.05) and improved sural sensory nerve conduction amplitude (p<0.05).

Conclusions/interpretation

This study demonstrates the efficacy of GLP-1 RAs in improving neuropathy outcomes, evidenced by improvements in mainly structural and morphological measures and supported by electrophysiological and clinical endpoints. Future studies, incorporating quantitative sensory testing and measurement of intraepidermal nerve fibre density, are needed to investigate the benefits for small fibre function and structure.

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Fig. 1

Abbreviations

CSA:

Cross-sectional area

DPN:

Diabetic peripheral neuropathy

DPP4:

Dipeptidyl peptidase-4

GLP-1:

Glucagon-like peptide-1

GLP-1 RA:

Glucagon-like peptide-1 receptor agonist

mTCNS:

Modified Toronto Clinical Neuropathy Scale

SGLT2:

Sodium–glucose cotransporter-2

TNS:

Total Neuropathy Score

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Authors and Affiliations

  1. School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia

    Roshan Dhanapalaratnam, Tushar Issar & Arun V. Krishnan

  2. Department of Neurology, Prince of Wales Hospital, Sydney, NSW, Australia

    Roshan Dhanapalaratnam & Arun V. Krishnan

  3. Department of Endocrinology, Prince of Wales Hospital, Sydney, NSW, Australia

    Alexandra T. K. Lee, Ann M. Poynten & Kerry-Lee Milner

  4. School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW, Australia

    Natalie C. G. Kwai

Authors
  1. Roshan Dhanapalaratnam
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  2. Tushar Issar
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  3. Alexandra T. K. Lee
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  4. Ann M. Poynten
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  5. Kerry-Lee Milner
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  6. Natalie C. G. Kwai
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  7. Arun V. Krishnan
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Corresponding author

Correspondence to Arun V. Krishnan.

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Acknowledgements

The Total Neuropathy Score was provided to AVK by D. Cornblath and Johns Hopkins University. We are grateful to the staff and patients of the Diabetes Centre at Prince of Wales Hospital, Sydney.

Data availability

The data that support the findings of this study are not publicly available due to institutional ethics review board restrictions (Human Research Ethics Committee of the South Eastern Sydney Local Health District HREC Ref. 14/012).

Funding

This research was supported by an Australian Government Research Training Program Scholarship.

Authors’ relationships and activities

The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

Contribution statement

RD, TI and AVK were involved in study design. RD, ATKL, AMP and K-LM carried out recruitment of participants. RD and ATKL performed the data collection. RD, TI, AMP, K-LM, NCGK and AVK were involved in data interpretation and TI, AMP, K-LM and NCGK were involved in discussion of the data. RD, TI and AVK wrote the manuscript. K-LM, AMP, ATKL and NCGK critically reviewed the manuscript for intellectual content. All authors approved the final version of the manuscript. AK is the guarantor of this work. As such, he had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Dhanapalaratnam, R., Issar, T., Lee, A.T.K. et al. Glucagon-like peptide-1 receptor agonists reverse nerve morphological abnormalities in diabetic peripheral neuropathy. Diabetologia 67, 561–566 (2024). https://doi.org/10.1007/s00125-023-06072-6

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  • DOI: https://doi.org/10.1007/s00125-023-06072-6

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