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Long-acting exenatide does not prevent cognitive decline in mild cognitive impairment: a proof-of-concept clinical trial.
Dei Cas, A; Micheli, M M; Aldigeri, R; Gardini, S; Ferrari-Pellegrini, F; Perini, M; Messa, G; Antonini, M; Spigoni, V; Cinquegrani, G; Vazzana, A; Moretti, V; Caffarra, P; Bonadonna, R C.
Afiliación
  • Dei Cas A; Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126, Parma, Italy. alessandra.deicas@unipr.it.
  • Micheli MM; Division of Nutritional and Metabolic Sciences, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126, Parma, Italy. alessandra.deicas@unipr.it.
  • Aldigeri R; Division of Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Gardini S; Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Ferrari-Pellegrini F; Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Perini M; Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Messa G; Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Antonini M; Center for Cognitive Disorders, AUSL Parma, Via Verona 36, Parma, Italy.
  • Spigoni V; Division of Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Cinquegrani G; Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Vazzana A; Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Moretti V; Division of Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Caffarra P; Division of Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126, Parma, Italy.
  • Bonadonna RC; Department of Medicine and Surgery, Section of Neuroscience, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
J Endocrinol Invest ; 47(9): 2339-2349, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38565814
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Disfunción Cognitiva / Exenatida / Hipoglucemiantes Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Endocrinol Invest Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Italia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Disfunción Cognitiva / Exenatida / Hipoglucemiantes Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Endocrinol Invest Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Italia