研究目的:探討口服降血糖藥物Metformin是否增加罹患阿茲海默 症的風險。 研究方法與設計:本研究採用病例對照研究(case-control study)設計,資料來源為台灣健保資料庫1999年糖尿病人抽樣歸人檔(Longitudinal Cohort of Diabetes Patients, LHDB)。自1999/1/1至2011/12/31共篩選66293位使用降血糖藥物第二型糖尿病個案。採用risk-set sampling界定罹患阿茲海默症為病例(case)個案,並採用傾向分數(propensity score)進行對照組個案配對。統計方法使用條件式邏輯斯迴歸(conditional logistic regression)分析使用Metformin藥物與罹患阿茲海默症之風險。 研究結果:在872位阿茲海默症發生病例中,共有690位(79.1%)曾使用Metformin藥物,而在3488位對照個案中,則有2607位(74.7%)曾使用Metformin藥物。在年齡大於或等於65歲者中,使用Metformin藥物者與阿茲海默症校正後有達統計學顯著相關,且勝算比(Odds Ratio, OR)為OR = 1.28 ( 95%C.I = 1.03-1.59)。於使用頻率分類結果方面,顯示正在使用(current use) Metformin藥物校正後的勝算比為OR = 2.88 (95%C.I = 2.20-3.79);平均每天使用劑量小於或等於1000毫克勝算比為OR = 1.39 (95%C.I = 1.11-1.74);累積使用年數小於或等於3年以下者勝算比為OR = 1.27 (95%C.I = 1.02-1.58),以及累積劑量較低者勝算比為OR =1.29 (95%C.I=1.01-1.65)。以上結果均顯示有較高發生阿茲海默症的風險。 結論:有糖尿病且年齡大於或等於65歲者,以及正在使用Metformin藥物者,有顯著增加阿茲海默症的風險。而Metformin藥物在低劑量使用且使用年限愈短者的族群,則觀察到具有增加阿茲海默症風險的傾向,但其詳細機制有待未來研究進一步探討。
Objective:Several studies have shown that diabetes is associated with Alzheimer's diseasebut with conflicting results inrecent years. Therefore , we aim to investigate whether using oral hypoglycemic agentmetformin in type 2 diabetic patients increases the risk of developing Alzheimer's disease. Materials andMethods:This is a retrospective case-control study. Froma databank of Longitudinal Cohort of Diabetes Patients(LHDB)retrieved from national health insurance in Taiwan, we obtained 66,293 type 2 diabetic patients treated with oral hypoglycemic agents during 1999-2011. Risk-set sampling was used to define patients suffering from Alzheimer's disease, while propensity score was performedfor case pairing with control groups. Conditional logistic regression was used to analyzethe risk of developing Alzheimer's disease in type 2 diabetic patients treated withMetformin. Results:There were 872 patients diagnosed with Alzheimer's diseaseduring this cohort. Among these patients,79.1%(n=690) were treated with metformin,while in the control group (n=3488),74.7% (n=2607) were treated with metformin. Overall, the result shows statistically significant association between metforminuse and the development of Alzheimer's disease〔adjusted OR 1.28(95% CI 1.03-1.59)〕. Interestingly, diabetes patients with current use, low cumulative dose(≦1000 mg), low daily dose(≦0.5 DDD/day), and short duration(≦3 years)had significantly higher risk of developing Alzheimer's disease[adjusted OR(95% CI)of current use;low cumulative dose;low daily dose;short duration:2.88(2.20-3.79);1.29(1.01-1.65);1.39(1.11-1.74);1.27(1.02-1.58), respectively.] Conclusion:Among diabetes patients older than 65 years of age,increased risk of Alzheimer's disease under current using metformin was proved. Furthermore, low dose and short duration use of metformin also have higher risk in developing Alzheimer's disease.
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