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

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. •GLP-1 receptor agonists (RA) have become widely prescribed drugs (type 2 diabetes/weight loss).•GLP-1RA repurposing is being clinically evaluated in neurodegenerative disorders of the elderly.•Clinical trials of GLP-RAs are promising in Parkinson’s disease – Alzheimer studies are ongoing.•GLP-1RAs with action on GIP and other receptors are available and may offer greater benefit.•Selection of the best GLP-1RAs, most likely patients to respond and best time to treat is critical.