降血脂藥與新生糖尿病之統合研究

Lipid-Lowering Therapy Agents and Risk of New-Onset Diabetes: Meta-analysis

目的：過去的斯達汀類(statins)藥物研究發現，其對新生糖尿病有不同的結果，在此除statins外，我們多加分析常用的降脂治療藥物和其發展成新生糖尿病間的關係。方法：以EndNote X8.2內之PubMed搜尋2018年3月前之降脂治療藥物藥物試驗。使用I²檢測研究間的異質性，用隨機效應做統合分析，計算各類藥物新生糖尿病的勝算比(OR)。使用RevMan 5.3統計軟體計算OR及95%信賴區間，再以MS-Excel畫森林圖。結果：共引用10篇文獻做統合分析，其中8篇為期刊，另2為具公信力之網路資料，結果發現高劑量statins增加新生糖尿病33%最嚴重(OR 1.33, 1.15-1.54)，整體之降脂治療藥物會增加新生糖尿病95%(OR 1.09, 1.03-1.15)，排除高劑量statins、膽固醇吸收抑制劑(ezetimibe)及枯草溶菌素轉化酶9抑制劑(PCSK9i)後，statins不會增加新生糖尿病(OR 1.07, 0.99-1.15)，然再排除pitavastatin，OR 1.08(1.003-1.15)會增加新生糖尿病8%的風險。Ezetimibe OR 1.04(0.94-1.16)，未達統計學上顯著差異。PCSK9i之FOURIER研究(evolocumab)之OR 1.05 (0.94-1.18)，alirocumab則為OR 0.92(0.42-2.01)，皆無增加新生糖尿病，且此類藥物次群組分析為OR 1.05(0.94-1.16)，亦未有顯著差異。結論：不同類型和劑量的降脂治療藥物之新生糖尿病亦不同，高劑量statins增加最多，整體降脂治療藥物及不含pitavastatin之statins亦會增加新生糖尿病，但個別的次群組分析皆未有顯著差異。

Objectives. Trials on the risk of incident diabetes associated with statin therapy have reported conflicting findings. In this meta-analysis, we investigated the relationship between the use of statins, and other commonly used lipid-lowering therapy(LLT) drugs and the risk of new-onset diabetes(NOD).
Methods. PubMed in EndNote X8.2 was searched for randomized controlled trials of statins and other lipid-lowering agents published until March 2018. We used the I²statistic to measure heterogeneity between trials and calculated the risk estimates for NOD with random-effect meta-analysis. The odds ratio(OR) with 95% CI were calculated with RevMan 5.3 software and the forest plots were drawn with MS-Excel 2016.
Results. Ten studies, including eight articles and data from two websites, were included in the meta-analysis. The results showed that intensive-dose statins increased risk of NOD by 33%(OR=1.33, 95% CI: 1.15-1.54), and the overall LLT drugs increased risk of NOD by 9%(OR=1.09, 95% CI: 1.03-1.15). After excluding intensive-dose statins, ezetimibe, and PCSK9i, we did not find the statins to increase NOD risk(OR=1.07, 95% CI: 0.99-1.15). Yet after excluding pitavastatin, the risk of NOD of statins increased by 8%(OR=1.08, 1.003-1.15). Ezetimibe study revealed no increased risk of NOD(OR=1.04, 95% CI: 0.94-1.16). In the FOURIER, evolocumab showed OR=1.05(95% CI: 0.94-1.18) and alirocumab showed OR=0.92(95% CI: 0.42-2.01). Subgroup analysis of the two PCSK9i drugs(OR=1.05, 95% CI: 0.94-1.16) showed no increased risk of NOD.
Conclusion. Different types and doses of LLT agents have different effects on risk of NOD. While intensive-dose statins increased risk of NOD the most, and all statins excluding pitavastatin and overall LLT also increased NOD, but individual subgroup analysis of all LLT agents did not reach statistical significance.