高齢糖尿病患者の認知症リスク低減に人気の薬が関連(Popular drug linked to reduced risk of dementia in older diabetes patients)

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2024-06-24 カロリンスカ研究所(KI)

カロリンスカ研究所による新しい研究によると、2型糖尿病を持つ高齢者がGLP-1アゴニストという薬を使用すると、認知症の発症リスクが低下することが示されました。この登録ベースの研究では、10年間にわたり88,000人以上の高齢者を追跡し、GLP-1アゴニスト、DPP-4阻害剤、スルホニル尿素薬の3種類の糖尿病治療薬と認知症リスクとの関連を分析しました。結果、GLP-1アゴニストを使用した患者は、スルホニル尿素薬を使用した患者に比べて認知症リスクが30%低く、DPP-4阻害剤を使用した患者に比べて23%低かったことがわかりました。この発見は、医師が2型糖尿病の高齢患者に対する治療薬の選択を改善するのに役立つ可能性があります。

<関連情報>

スウェーデンの高齢2型糖尿病患者における認知症リスクに対するグルカゴン様ペプチド-1作動薬、ジペプチジルペプチダーゼ-4阻害薬、スルホニル尿素薬の比較有効性:模擬試験研究 Comparative effectiveness of glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, and sulfonylureas on the risk of dementia in older individuals with type 2 diabetes in Sweden: an emulated trial study

Bowen Tang,Arvid Sjölander,Jonas W. Wastesson,Géric Maura,Pierre-Olivier Blotiere,Máté Szilcz,et al.
eClinicalMedicine  Published:June 20, 2024
DOI:https://doi.org/10.1016/j.eclinm.2024.102689

高齢糖尿病患者の認知症リスク低減に人気の薬が関連(Popular drug linked to reduced risk of dementia in older diabetes patients)

Summary

Background
The comparative effectiveness of glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas on the risk of dementia in older individuals with type 2 diabetes mellitus (T2DM) is unknown.

Methods
We conducted a sequential trial emulation from 1st January 2010 to 30th June 2020 using data from Swedish national registers. Swedish residents who were aged 65 or older, had type 2 diabetes (T2DM), and initiated GLP-1 agonists, DPP-4 inhibitors, or sulfonylureas were followed for up to 10 years to assess the risk of dementia. Participants who had dementia, used the three drug classes, or had contraindications were excluded from enrollment. The characteristics between arms were balanced through the application of propensity scores estimated from predefined covariates. Intention-to-treat effects were analysed with all enrolled participants, while the per-protocol effects were analysed with participants who adhered to the assigned treatment.

Findings
The pooled trial included 88,381 participants who received prescriptions for GLP-1 agonists (n = 12,351), DPP-4 inhibitors (n = 43,850), or sulfonylureas (n = 32,216) at baseline and were followed for an average of 4.3 years. A total of 4607 dementia cases developed during follow-up: 278 for the GLP-1 agonist initiators (incidence rate: 6.7 per 1000 person years), 1849 for DPP-4 inhibitor initiators (IR: 11.8), and 2480 for sulfonylurea initiators (IR: 13.7). In an intention-to-treat analysis, GLP-1 agonist initiation was associated with a reduced risk of dementia compared to sulfonylureas (hazard ratio: 0.69, 95% CI: 0.60–0.79, p < 0.0001) and DPP-4 inhibitors (HR: 0.77, 95% CI: 0.68–0.88, p < 0.0001), after adjusting for age, enrollment year, sex, socioeconomic factors, health conditions, and past medication uses. These findings were consistent in several sensitivity analyses, including a per-protocol analysis (HR for sulfonylureas: 0.41, 95% CI: 0.32–0.53, p < 0.0001; HR for DPP-4 inhibitors: 0.38, 95% CI: 0.30–0.49, p < 0.0001).

Interpretation
Our research suggested that GLP-1 agonists were associated with a lower risk of dementia compared to sulfonylureas and DPP-4 inhibitors in older individuals with T2DM. Further clinical trials are needed to validate these findings.

Funding
Swedish Research Council, Karolinska Institutet, the National Institute on Aging, the National Institutes of Health, and Riksbankens Jubileumsfond.

有機化学・薬学
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