TOPLINE:

Among diabetes drugs, GLP-1 receptor agonists and SGLT2 inhibitors were associated with greater reduction in the risk for Alzheimer’s disease (AD) than DPP-4 inhibitors, new research showed.

METHODOLOGY:

• Researchers analyzed data from two large real-world databases: Optum’s de-identified Clinformatics Data Mart database (2007-2021) and the Northwestern Medicine Enterprise Data Warehouse (2005-2023).
• Data included demographic variables, enrollment records, diagnosis records, pharmacy claims, and comprehensive clinical information.
• Three drug classes were analyzed: GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), and DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, and sitagliptin).
• Risk for AD was compared for GLP‑1 receptor agonists (n ≈ 64,000) vs DPP‑4 inhibitors (n ≈ 142,000), SGLT2 inhibitors (n ≈ 59,000) vs DPP-4 inhibitors, and GLP-1 receptor agonists vs SGLT2 inhibitors.

TAKEAWAY:

• In pooled analyses, use of GLP-1 inhibitors (hazard ratio [HR], ≤ 0.69; P < .001) or SGLT2 inhibitors (HR, ≤ 0.67; P < .001) was associated with reduced risk for AD compared to use of DPP-4 inhibitors. There were no significant differences in terms of AD between GLP-1 receptor agonists and SGLT2s inhibitors.
• GLP-1 receptor agonists were associated with a lower AD risk than DPP-4 inhibitors in women (HR, ≤ 0.66; P < .0001), White individuals (HR, ≤ 0.67; P < .0001), and individuals with obesity (HR, ≤ 0.72; P ≤ .002).
• SGLT2s inhibitors were associated with a lower AD risk than DPP-4 inhibitors in women (HR, ≤ 0.76; P ≤ .0002), men (HR, ≤ 0.55; P < .001), White individuals (HR, ≤ 0.64; P < .001), and individuals with obesity (HR, ≤ 0.70; P ≤ .008) or overweight (HR, ≤ 0.52; P ≤ .02).
• In drug-specific analyses, the GLP-1 receptor agonists liraglutide and semaglutide were linked to reduced AD risk (P ≤ .01), as were the SGLT2s inhibitors dapagliflozin, canagliflozin, and empagliflozin (P ≤ .04).

IN PRACTICE:

“GLP-1 receptor agonists and SGLT2 inhibitors may offer potential prevention or treatment effects for AD,” the investigators wrote.

“Randomized controlled trials in diverse populations are highly warranted to further test clinically beneficial effects of GLP-1 receptor agonists and SGLT-2 inhibitors,” they added.

SOURCE:

The study was led by Pengyue Zhang, PhD, Indiana University, Indianapolis. It was published online on September 2 in Alzheimer’s & Dementia.

LIMITATIONS:

Data were limited to individuals in the two databases, potentially affecting generalizability. The results were not applicable to those without insurance, retirees without Medicare supplemental plans, and those not initiating the studied medications. The findings may have been influenced by unmeasured confounding effects related to such factors as socioeconomic status, smoking status, blood glucose levels, and missing weight data. Neurologic exams, cognitive tests, and brain images were not included, and biological confirmation of AD diagnosis was unavailable. 

DISCLOSURES:

The study was funded primarily by the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. Three investigators reported having financial or consultancy ties with various pharmaceutical, assessment, and investment companies, which are fully listed in the original article. Zhang and the other eight investigators reported having no relevant financial relationships.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.