Different drug treatments may induce severe hypoglycemia to type 2 diabetes mellitus patients

目的 嚴重低血糖是第二型糖尿病患者的重要副作用，其可能增加病患生理與心理及經濟的負擔，過去已知不同的藥物使用可能使得病患具有產生嚴重低血糖的不同風險值，因此本論文運用美國糖尿病治療指引作為藥物分類的參考依據，進一步釐清在何種藥物組合下第二型糖尿病患會有較高的嚴重低血糖風險。 方法 本研究使用國家衛生研究院全民健康保險研究資料庫承保抽樣百萬歸人檔，探討2008年至2011年第二型糖尿病患且使用藥物之新發病患，分析索引日期前不同藥物治療方式罹患嚴重低血糖的風險。嚴重低血糖病患的索引日期定義為在研究期間內發生嚴重低血糖住院或尋求協助之時間，而對照組的索引日期則定義為病患在研究日期的最後一天追蹤日期。為了探索不同的藥物組合是否具有誘發嚴重低血糖不一樣的風險情形，我們使用Cox風險模型進行分析。 結果 經過一連串篩選條件以及傾向分數配對後，本研究納入的分析族群共有嚴重低血糖204人，對照組816人。在控制性別、年齡、病齡及察爾森共病指數等干擾變項後，統計分析結果顯示第二型糖尿病病患使用胰島素合併其它藥物發生嚴重低血糖的風險最高，其勝算比為9.63(4.40-21.08)，若進一步將病患根據年齡切割成不同族群，結果顯示≧65歲之老年病患在使用胰島素合併其它藥物發生嚴重低血糖的風險最高，其勝算比為12.67(4.15-38.62)。 結論 本論文使用健保資料庫分析之第二型糖尿病族群以使用口服藥物者較多，而發生嚴重低血糖之病患則大多使用合併藥物，藥物組合中則以使用胰島素合併其它藥物發生嚴重低血糖風險最高，同樣的情形可以在年齡≧65歲的病患上觀察到。因此，未來針對使用胰島素合併其他藥物之第二型糖尿病病患應加強其衛教，以減少嚴重低血糖副作用之發生。Objective Severe hypoglycemia is a severe side effect of type 2 diabetes (T2D), which is able to increase the burden of psychological, physiological and economy in the patients. To address which populations of T2D patients are susceptible to severe hypoglycemia, we classified the T2D patients into different groups based on the clinical guidelines developed by the American Diabetes Association. Specifically, this study aims to explore the causal associations between the combinations of antidiabetic drugs and severe hypoglycemia. Methods We used the data collected from the National Health Insurance Research database (NHIRD) during 2008-2011 in Taiwan. This study employed a nested case-control study design to investigate the newly diagnosed T2D patients. Severe hypoglycemia case group was defined as the patients underwent the hypoglycemia and sought the help from a hospital. For the case group, the date for the hospitalization or the event was called as the index date; whereas, for the control group, the last day of the following day in the studied period was defined as the index date. To analyze the associations of the combinations of drugs and severe hypoglycemia, a Cox hazard regression model was utilized. Results To minimize the potential biases from confounding factors, we matched the case group by using the propensity score method based on the one to fourth design. The results revealed 204 cases with severe hypoglycemia and 816 matched controls. Statistical analysis of the associations between drug combinations and hypoglycemia revealed the highest odds ratio (9.63, 95% CI: 4.40-21.08) in the T2D patients concurrently using insulin and other drugs. Similar high odds ratio (12.67, 95% CI: 4.15-38.62) was observed in the elder T2D patients, whose age was higher than 65. Conclusion The results of this study indicated that the T2D patients from the NHIRD had a higher proportion to take oral drugs and intriguingly most patients in the case group of hypoglycemia used multiple drugs simultaneously. The statistical results showed that the T2D patients had the highest odds ratio while concurrently using insulin and other drugs. The same phenomenon can be observed in the elder T2D patients, whose age was higher than 65. Consequently, we shall provide detailed health education for the T2D patients to prevent the occurrence of hypoglycemia while they concurrently use insulin and other drugs