TOPLINE:

The initiation of GLP-1 agonists was associated with a lower risk for Alzheimer’s disease and related dementias than the initiation of DPP-4 inhibitors in patients with diabetes undergoing hemodialysis; however, it was also linked to an increased risk for diabetic ketoacidosis.

METHODOLOGY:

• GLP-1s are associated with a reduced risk for dementia in the general population, but it is unclear if this benefit extends to patients with diabetes requiring chronic in-center hemodialysis.
• Researchers emulated a target trial using the United States Renal Data System database to compare the effectiveness of GLP-1s vs DPP-4 inhibitors for incident Alzheimer’s disease and related dementias in patients with type 2 diabetes receiving hemodialysis who had no prior history of dementia.
• They compared 3492 new users of GLP-1s with 11,609 new users of DPP-4 inhibitors; both groups had a mean age of 63 years, and 52% were male. All participants had received hemodialysis for at least 90 days and had no prescriptions for either drug in the previous 180 days.
• The primary outcome was the first diagnosis of Alzheimer’s disease and related dementias; secondary outcomes included diagnoses of specific subtypes, such as dementia not otherwise specified, vascular dementia, and Alzheimer’s dementia.
• Follow-up started at medication dispensing, with a median duration of 1.5 years.

TAKEAWAY:

• When patients were analyzed according to the assigned treatment, those who began GLP-1s had an 18% lower risk of developing Alzheimer’s disease or related dementias than those who began DPP-4 inhibitors (subdistribution hazard ratio [sHR], 0.82; 95% CI, 0.67-0.98).
• The reduction was significant only for the “dementia not otherwise specified” subtype.
• Although adherence at 1 year was slightly lower for GLP-1s than for DPP-4 inhibitors (31% vs 38%), the protective association persisted in analyses based on treatment actually received by the patients (sHR, 0.61; 95% CI, 0.47-0.78).
• GLP-1s were associated with an increased risk for ketoacidosis (sHR, 1.52; 95% CI, 1.14-2.02).

IN PRACTICE:

“Our results suggest the potential effectiveness for GLP-1s in reducing ADRD [Alzheimer’s disease and related dementias] risk for patients requiring in-center hemodialysis,” the authors of the study wrote.

SOURCE:

The study was led by Dustin Le, Thomas Jefferson University, Philadelphia. It was published online in Diabetes Care.

LIMITATIONS:

Data on key factors such as A1c level, diabetes duration, frailty status, and baseline cognitive function were unavailable. Reliance on diagnostic codes for defining study outcomes and covariates may have led to misclassification. Generalizability is limited because all patients had Medicare Parts A, B, and D as their primary payer for at least 6 months prior to medication dispensing.

DISCLOSURES:

The study was supported by the National Kidney Foundation and the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The authors of the study reported having no relevant conflicts of interest.

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