Drug design, development and therapy · 2026
GLP-1 Receptor Agonists Versus DPP-4 Inhibitors and Incident Dementia Risk in COVID-19 Survivors with Type 2 Diabetes: A Target Trial Emulation Study.
СтатьяСравнительное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Hung Kuo-Chuan, Yu Ting-Sian, Liu Ping-Hsin, Lai Yi-Chen, Chen I-Wen
Аннотация
PURPOSE: Type 2 diabetes mellitus (T2DM) and COVID-19 are independently associated with an elevated risk of dementia, and COVID-19 survivors with T2DM may represent a clinically vulnerable population in whom metabolic, inflammatory, and vascular factors coexist. However, whether antidiabetic treatment choice is associated with incident dementia risk in this population remains unknown.
METHODS: In this target trial emulation using the TriNetX US Collaborative Network, we compared COVID-19 survivors aged ≥50 years with T2DM initiating glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy with those initiating dipeptidyl peptidase-4 inhibitor (DPP-4i) therapy between January 1, 2020 and December 31, 2024. We applied an active-comparator, new-user design with a 90-day survivor landmark and 1:1 propensity score matching. The primary outcome was incident all-cause dementia (a composite of vascular dementia, Alzheimer's disease, and other dementias). Secondary outcomes included dementia subtypes, mild cognitive impairment, glycemic outcomes, and all-cause mortality.
RESULTS: After matching, 25,263 patients per group were followed for up to 6 years (median, 919 days [GLP-1RA] vs 955 days [DPP-4i]). GLP-1RA initiation was associated with a lower hazard of incident dementia (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.58-0.72), vascular dementia (HR, 0.67; 95% CI, 0.52-0.85), and Alzheimer's disease (HR, 0.74; 95% CI, 0.59-0.93), as well as more favorable glycemic control and lower all-cause mortality (HR, 0.63; 95% CI, 0.59-0.68). The estimate for mild cognitive impairment was borderline (HR, 0.87; 95% CI, 0.75-1.00) and not consistently supported across sensitivity analyses. The association with incident dementia remained evident after the 6-month landmark analysis (HR, 0.66; 95% CI, 0.58-0.75) and was consistent across sensitivity and subgroup analyses.
CONCLUSION: Among COVID-19 survivors with T2DM, GLP-1RA initiation was associated with a lower hazard of incident dementia than DPP-4i initiation. These hypothesis-generating results warrant confirmation before they can be used to inform clinical decision-making.
METHODS: In this target trial emulation using the TriNetX US Collaborative Network, we compared COVID-19 survivors aged ≥50 years with T2DM initiating glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy with those initiating dipeptidyl peptidase-4 inhibitor (DPP-4i) therapy between January 1, 2020 and December 31, 2024. We applied an active-comparator, new-user design with a 90-day survivor landmark and 1:1 propensity score matching. The primary outcome was incident all-cause dementia (a composite of vascular dementia, Alzheimer's disease, and other dementias). Secondary outcomes included dementia subtypes, mild cognitive impairment, glycemic outcomes, and all-cause mortality.
RESULTS: After matching, 25,263 patients per group were followed for up to 6 years (median, 919 days [GLP-1RA] vs 955 days [DPP-4i]). GLP-1RA initiation was associated with a lower hazard of incident dementia (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.58-0.72), vascular dementia (HR, 0.67; 95% CI, 0.52-0.85), and Alzheimer's disease (HR, 0.74; 95% CI, 0.59-0.93), as well as more favorable glycemic control and lower all-cause mortality (HR, 0.63; 95% CI, 0.59-0.68). The estimate for mild cognitive impairment was borderline (HR, 0.87; 95% CI, 0.75-1.00) and not consistently supported across sensitivity analyses. The association with incident dementia remained evident after the 6-month landmark analysis (HR, 0.66; 95% CI, 0.58-0.75) and was consistent across sensitivity and subgroup analyses.
CONCLUSION: Among COVID-19 survivors with T2DM, GLP-1RA initiation was associated with a lower hazard of incident dementia than DPP-4i initiation. These hypothesis-generating results warrant confirmation before they can be used to inform clinical decision-making.