Type 2 diabetes mellitus/obesity drugs: A neurodegenerative disorders savior or a bridge too far?

Katherine O Kopp; Elliot J Glotfelty; Yazhou Li; Debomoy K Lahiri; Nigel H Greig

doi:10.1016/j.arr.2024.102343

Type 2 diabetes mellitus/obesity drugs: A neurodegenerative disorders savior or a bridge too far?

Ageing Res Rev. 2024 May 16:98:102343. doi: 10.1016/j.arr.2024.102343. Online ahead of print.

Authors

Katherine O Kopp¹, Elliot J Glotfelty², Yazhou Li³, Debomoy K Lahiri⁴, Nigel H Greig⁵

Affiliations

¹ Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: katherine.kopp@nih.gov.
² Cellular Stress and Inflammation Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
³ Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
⁴ Department of Psychiatry, Indiana Alzheimer Disease Research Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medical & Molecular Genetics, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁵ Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: Greign@grc.nia.nih.gov.

PMID: 38762101
DOI: 10.1016/j.arr.2024.102343

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonist-based drugs (incretin mimetics) have meaningfully impacted current treatment of type 2 diabetes mellitus (T2DM), and their actions on satiety and weight loss have led to their use as an obesity medication. With multiple pleotropic actions beyond their insulinotropic and weight loss ones, including anti-inflammatory and anti-insulin-resistant effects selectively mediated by their receptors present within numerous organs, this drug class offers potential efficacy for an increasing number of systemic and neurological disorders whose current treatment is inadequate. Among these are a host of neurodegenerative disorders that are prevalent in the elderly, such as Parkinson's and Alzheimer's disease, which have bucked previous therapeutic approaches. An increasing preclinical, clinical, and epidemiological literature suggests that select incretin mimetics may provide an effective treatment strategy, but 'which ones' for 'which disorders' and 'when' remain key open questions.

Keywords: Alzheimer’s disease; Glucagon-like peptide-1 (GLP-1); Glucose-dependent insulinotropic polypeptide (GIP); Incretin mimetic; Insulin resistance; Neurodegeneration; Neuroinflammation; Parkinson’s disease; Type 2 diabetes mellitus.

Publication types

Review