比較第二型糖尿病患者以metformin及sulfonylurea治療仍控制不良時加上pioglitazone或sitagliptin之療效

Abstract

背景與研究目的：第2型糖尿病是一種進行性的慢性疾病，往往需要逐漸增加降血糖藥物才能有效控制血糖。metformin及sulfonylurea為最常見的治療組合，且是一些治療指引建議的第一線與第二線口服降血糖藥物。但隨著疾病的進行血糖往往無法達到治療目標，此時需要加上其他降血糖藥物來控制血糖。pioglitazone(愛妥糖)與sitagliptin (佳糖維)常被用來當作第三線的治療藥物，但沒有研究直接比較兩種藥物在治療效果與副作用上的差異。 研究對象與方法：已經用metformin(≥1500mg/d)及sulfonylurea(≥ half maximal dose)治療仍控制不良(糖化血色素≥7.0 % and <11%)的第2型糖尿病患者，隨機分配加上pioglitazone(每日一錠30毫克；59人) 或sitagliptin (每日一錠100毫克；60人) 治療24周。 結果：糖化血色素在pioglitazone組與sitagliptin組分別下降0.94± 0.12 %與0.71± 0.12 %，兩組間沒有差異(-0.23±0.16 %；p=0.16)。 pioglitazone組有28.8%、sitagliptin組有28.3%的患者達到糖化血色素小於7.0%的目標。空腹血糖在pioglitazone組與sitagliptin組分別下降35.7± 4. 0mg/dl 與22.8± 4.0mg/dl，兩組之間有顯著的差異(-12.9±5.7mg/dl；p=0.02)。HOMA-IR、三酸甘油脂與high sensitive CRP在pioglitazone組顯著比sitagliptin組下降較多，而高密度膽固醇在pioglitazone組顯著比sitagliptin組升高。治療後pioglitazone組顯著比sitagliptin組體重增加1.6±0.5公斤。整體上兩組在副作用與低血糖發生的比率上沒有差異，但pioglitazone組周邊水腫發生的機會較高(27% vs. 0%)，而sitagliptin組腸胃道副作用發生的機會較高(20%vs.6.8%)。 結論：糖尿病患者以metformin及sulfonylurea治療仍控制不良時加上pioglitazone或sitagliptin之療效相當。但兩組在空腹血糖、HOMA-IR、三酸甘油脂、高密度膽固醇、high sensitive CRP與體重的變化上有顯著的異。

Background: Type 2 diabetes is a progressive illness which most patients experience a progressive deterioration in glycemic control, dual combination therapy with metformin and a sulfonylurea also may not achieve or maintain glycemic control. Objective: To evaluate the efficacy and safety of add-on pioglitazone vs. sitagliptin in patients with type 2 diabetes inadequately controlled on dual therapy. Methods: This 24-week, randomized, open-label, randomized, parallel study compared pioglitazone (30 mg daily, n=59) and sitagliptin (100 mg daily, n=60) in patients with inadequate glycemic control (glycosylated hemoglobin A1c [A1C] ≥7.0% to <11.0%) while receiving a stable dose of metformin (≥1500 mg daily) and a sulfonylureas (≥half maximal dose). Results: Mean (±s.e.) change in A1C from baseline was -0.94± 0.12 % with pioglitazone and -0.71± 0.12 % with sitagliptin, for a between groups difference of -0.23±0.16 % (p=0.16). The percentages of patient achieving A1C <7% were 28.8% and 28.3% in the pioglitazone and sitagliptin groups, respectively. Mean change in fasting plasma glucose were -35.7± 4.0mg/dl with pioglitazone and -22.8± 4.0mg/dl with sitagliptin, for a between groups difference of-12.9±5.7mg/dl (p=0.02). Pioglitazone was associated with significant decrease in HOMA-IR, triglyceride, hs-CRP and increase high-density lipoprotein cholesterol, while sitagliptin did not induce changes in these parameters. Mean weight gain was higher in the pioglitazone group with a between-group difference of 1.60kg (p<0.01). Overall adverse events and the rate of hypoglycemia were similar in both groups. However, the incident of edema was higher with pioglitazone vs. sitagliptin (27% vs. 0%) and the incident of gastrointestinal adverse events was higher with sitagliptin vs. pioglitazone (20% vs.6.8%). Conclusions: Pioglitazone and sitagliptin achieved similar improvements in overall glycemic control in patients with type 2 diabetes inadequately controlled with metformin and a sulfonylurea. However there were some differences in terms of FPG, lipids, HOMA-IR, body weight change and adverse events.