Clinical relevance between sodium-glucose co-transporter 2 inhibitors and lipid profiles in Asian patients with type 2 diabetes mellitus: a systematic review with a meta-analysis of randomized controlled trials

BACKGROUND: 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. METHODS: 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. RESULTS: 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)%, p < 0.00001], TG [mean difference − 16.42 (95%CI − 22.71 to − 10.12) mg/dL, p < 0.00001], and HDL-C [mean difference 3.36 (95%CI 2.73 to 3.98) mg/dL, p < 0.00001], but significantly deteriorated LDL-C [mean difference 3.00 (95%CI 1.18 to 4.82) mg/dL, p < 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), p < 0.74]. CONCLUSION: 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.