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Journal of Endocrinological Investigation

Open Access 02-04-2024 | Exenatide | Original Article

Long-acting exenatide does not prevent cognitive decline in mild cognitive impairment: a proof-of-concept clinical trial

Authors: A. Dei Cas, M. M. Micheli, R. Aldigeri, S. Gardini, F. Ferrari-Pellegrini, M. Perini, G. Messa, M. Antonini, V. Spigoni, G. Cinquegrani, A. Vazzana, V. Moretti, P. Caffarra, R. C. Bonadonna

Published in: Journal of Endocrinological Investigation

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Abstract

Purpose

According to preclinical evidence, GLP-1 receptor may be an actionable target in neurodegenerative disorders, including Alzheimer’s disease (AD). Previous clinical trials of GLP-1 receptor agonists were conducted in patients with early AD, yielding mixed results. The aim was to assess in a proof-of-concept study whether slow-release exenatide, a long-acting GLP-1 agonist, can benefit the cognitive performance of people with mild cognitive impairment (MCI).

Methods

Thirty-two (16 females) patients were randomized to either slow-release exenatide (n = 17; 2 mg s.c. once a week) or no treatment (n = 15) for 32 weeks. The primary endpoint was the change in ADAS-Cog11 cognitive test score at 32 weeks vs baseline. Secondary endpoints herein reported included additional cognitive tests and plasma readouts of GLP-1 receptor engagement. Statistical analysis was conducted by intention to treat.

Results

No significant between-group effects of exenatide on ADAS-Cog11 score (p = 0.17) were detected. A gender interaction with treatment was observed (p = 0.04), due to worsening of the ADAS-Cog11 score in women randomized to exenatide (p = 0.018), after correction for age, scholar level, dysglycemia, and ADAS-Cog score baseline value. Fasting plasma glucose (p = 0.02) and body weight (p = 0.03) decreased in patients randomized to exenatide.

Conclusion

In patients with MCI, a 32-week trial with slow-release exenatide had no beneficial effect on cognitive performance.

Trial registration number

NCT03881371, registered on 21 July, 2016.
Appendix
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Metadata
Title
Long-acting exenatide does not prevent cognitive decline in mild cognitive impairment: a proof-of-concept clinical trial
Authors
A. Dei Cas
M. M. Micheli
R. Aldigeri
S. Gardini
F. Ferrari-Pellegrini
M. Perini
G. Messa
M. Antonini
V. Spigoni
G. Cinquegrani
A. Vazzana
V. Moretti
P. Caffarra
R. C. Bonadonna
Publication date
02-04-2024
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-024-02320-7
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