口服SGLT2 inhibitors排糖藥物(canagliflozin, dapagliflozin, and empagliflozin) 潛在 ketoacidosis(酮酸中毒)風險

最新口服排糖藥物 深受醫病期待 2015-09-04 03:02:43 聯合報 文／丁志榮分享根據2013年國際糖尿病聯盟（IDF）資料，台灣糖尿病的罹患人數已突破170萬人大關，盛行率約為9.8%，相當於每10個台灣人就有1位是糖尿病患；另外2011年，台灣糖尿病健康促進機構品管調查顯示，仍有6成5的患者控制血糖尚未達標。糖尿病若未能妥善控制，很可能激化大血管病變，引發心肌梗塞、中風，甚至截肢。 一名60多歲的男性糖尿病病友，罹患糖尿病已經8年，糖化血色素（HbA1c）總是無法達標（小於7%），經醫師評估後調整服藥處方，短短兩個月內發現糖化血色素降至6.5%，體重更從80公斤降至76公斤，經醫師解說才知道，「這是改用口服排糖藥的結果」。財團法人糖尿病關懷基金會執行長蔡世澤指出，去年底經衛福部食藥署核准的台灣第一個口服排糖藥物（SGLT2抑制劑），是透過阻斷腎小管對葡萄糖再吸收，讓身體每天從尿液排除約78公克的葡萄糖到體外（熱量約等於一碗白飯），不僅達到降糖效果，順便也降低體重。此類藥物除了單獨使用，也適合在任何需要加藥控制血糖的時候與其他口服藥物或胰島素合併使用。最近外電報導，即將發表的EMPA-REG OUTCOME長期臨床研究（中位數3.1年）顯示，此口服排糖藥物對於第二型糖尿病患因心血管疾病死亡、或第一次發生非致死性心肌梗塞、或第一次發生非致死性中風的風險有顯著降低，是目前所知唯一可降低心血管事件風險的降血糖藥物，從而增加醫師對此種藥物的期待。希望未來健保給付通過後，可以造福更多糖尿病友。蔡世澤也特別提醒，使用這類口服排糖藥物（SGLT2抑制劑）至少每天要多喝一杯水，才能將糖分從尿中排除，同時也要注意個人衛生習慣，避免泌尿生殖道感染。凡75歲以下成年人且腎功能良好（腎功能指數eGFR高於45mL/min/1.73m2）的第二型糖尿病患者，都可視病情選擇使用。

FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood  FDA [ 05-15-2015 ] The U.S. Food and Drug Administration (FDA) is warning that the type 2 diabetes medicines canagliflozin, dapagliflozin, and empagliflozin may lead to ketoacidosis, a serious condition where the body produces high levels of blood acids called ketones that may require hospitalization. We are continuing to investigate this safety issue and will determine whether changes are needed in the prescribing information for this class of drugs, called sodium-glucose cotransporter-2 (SGLT2) inhibitors. Patients should pay close attention for any signs of ketoacidosis and seek medical attention immediately if they experience symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness. Do not stop or change your diabetes medicines without first talking to your prescriber. Health care professionals should evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing these signs or symptoms; discontinue SGLT2 inhibitors if acidosis is confirmed; and take appropriate measures to correct the acidosis and monitor sugar levels. SGLT2 inhibitors are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. When untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. SGLT2 inhibitors lower blood sugar by causing the kidneys to remove sugar from the body through the urine. These medicines are available as single-ingredient products and also in combination with other diabetes medicines such as metformin (see Table 1 below). The safety and efficacy of SGLT2 inhibitors have not been established in patients with type 1 diabetes, and FDA has not approved them for use in these patients. A search of the FDA Adverse Event Reporting System (FAERS) database identified 20 cases of acidosis reported as diabetic ketoacidosis (DKA), ketoacidosis, or ketosis in patients treated with SGLT2 inhibitors from March 2013 to June 6, 2014 (see Data Summary). All patients required emergency room visits or hospitalization to treat the ketoacidosis. Since June 2014, we have continued to receive additional FAERS reports for DKA and ketoacidosis in patients treated with SGLT2 inhibitors. DKA, a subset of ketoacidosis or ketosis in diabetic patients, is a type of acidosis that usually develops when insulin levels are too low or during prolonged fasting. DKA most commonly occurs in patients with type 1 diabetes and is usually accompanied by high blood sugar levels. The FAERS cases were not typical for DKA because most of the patients had type 2 diabetes and their blood sugar levels, when reported, were only slightly increased compared to typical cases of DKA. Factors identified in some reports as having potentially triggered the ketoacidosis included major illness, reduced food and fluid intake, and reduced insulin dose. We urge health care professionals and patients to report side effects involving SGLT2 inhibitors to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of the page.

 

SGLT2 inhibitors, Brand name (Active ingredient)

Invokana  (canagliflozin)

Invokamet (canagliflozin and metformin)

Farxiga (dapagliflozin)

Xigduo XR (dapagliflozin and metformin extended-release)

Jardiance (empagliflozin)

Glyxambi (empagliflozin and linagliptin)