Mukai Junichi, Yoshiyama Ayano, Kubota Rie
Division of Clinical Pharmacy (Laboratory of Clinical Pharmacy Education) and Research and Education Center for Clinical Pharmacy, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641 Japan.
J Pharm Health Care Sci. 2020 Mar 14;6:4. doi: 10.1186/s40780-020-00160-0. eCollection 2020.
Few systematic reviews have examined the effects of sodium-glucose co-transporter 2 inhibitors (SGLT2is) on lipid profiles in Asian patients with type 2 diabetes mellitus. We conducted a systematic review with a meta-analysis to summarize the available literature and confirm the effects of SGLT2is on lipid profiles in these patients.
We searched the electronic databases MEDLINE, CENTRAL, and Ichushi-web for studies from the dates of their earliest publication to July 2018, and there was no language restriction. Trials were included if they were randomized controlled trials (RCTs) (1) comparing the effects of SGLT2is with a placebo in Asian patients with type 2 diabetes mellitus (18 years or older), and (2) reporting HbA1c and at least one lipid parameter, such as triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C). The weighted mean difference with a 95% confidence interval (CI) was calculated using a random-effects model.
Among the 630 studies retrieved, 17 RCTs that included 4485 patients were ultimately included in our review. Fourteen RCTs were conducted in Japan. The durations of RCTs ranged between 12 and 24 weeks. SGLT2is significantly improved HbA1c [mean difference - 0.80 (95%CI - 0.96 to - 0.64)%, < 0.00001], TG [mean difference - 16.42 (95%CI - 22.71 to - 10.12) mg/dL, < 0.00001], and HDL-C [mean difference 3.36 (95%CI 2.73 to 3.98) mg/dL, < 0.00001], but significantly deteriorated LDL-C [mean difference 3.00 (95%CI 1.18 to 4.82) mg/dL, < 0.001]. The LDL-C/HDL-C ratio was not significantly different between SGLT2is and a placebo [mean difference - 0.01 (95%CI - 0.08 to 0.06), < 0.74].
The present results suggest that in Asian patients with type 2 diabetes mellitus, TG and HDL-C values were better, while LDL-C values were worse with SGLT2is than with a placebo. However, the negative impact of SGLT2is on lipid profiles was modest. Further RCTs with a longer duration or conducted in other Asian countries are needed to provide further evidence to support the clinical relevance of changes in lipid profiles. The present results will be informative for SGLT2is users with concerns regarding the effects of SGLT2is on lipid profiles.
很少有系统评价研究钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）对亚洲2型糖尿病患者血脂谱的影响。我们进行了一项系统评价和荟萃分析，以总结现有文献并确认SGLT2i对这些患者血脂谱的影响。
我们检索了电子数据库MEDLINE、CENTRAL和Ichushi-web，查找从最早发表日期至2018年7月的研究，且无语言限制。纳入的试验需为随机对照试验（RCT）：（1）比较SGLT2i与安慰剂对18岁及以上亚洲2型糖尿病患者的影响；（2）报告糖化血红蛋白（HbA1c）和至少一项血脂参数，如甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）或低密度脂蛋白胆固醇（LDL-C）。采用随机效应模型计算加权平均差及95%置信区间（CI）。
在检索到的630项研究中，最终有17项RCT纳入我们的评价，共4485例患者。14项RCT在日本进行。RCT的持续时间为12至24周。SGLT2i显著改善了HbA1c[平均差-0.80（95%CI -0.96至-0.64）%，P<0.00001]、TG[平均差-16.42（95%CI -22.71至-10.12）mg/dL，P<0.00001]和HDL-C[平均差3.36（95%CI 2.73至3.98）mg/dL，P<0.00001]，但显著恶化了LDL-C[平均差3.00（95%CI 1.18至4.82）mg/dL，P<0.001]。SGLT2i与安慰剂之间的LDL-C/HDL-C比值无显著差异[平均差-0.01（95%CI -0.08至0.06），P<0.74]。
目前的结果表明，在亚洲2型糖尿病患者中，与安慰剂相比，SGLT2i使TG和HDL-C值改善，而LDL-C值恶化。然而，SGLT2i对血脂谱的负面影响较小。需要进行持续时间更长或在其他亚洲国家开展的进一步RCT，以提供更多证据支持血脂谱变化的临床相关性。本研究结果将为关注SGLT2i对血脂谱影响的使用者提供参考。
