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

Abstract

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].

Neutral effect of SGLT2 inhibitors on lipoprotein metabolism: From clinical evidence to molecular mechanisms

“…When analysed in detail, empagliflozin produced the highest increase in total cholesterol (4.25 mg/dL, 0.11 mmol/L), while canagliflozin showed the largest effect in increasing LDL-C (5.03 mg/dL, 0.13 mmol/L) [35]. Similar results were observed in another meta-analysis of 17 RCTs including 4485 Asian diabetic patients (Table 2) [36].…”

Lipid effects of sodium-glucose cotransporter 2 inhibitors

“…In contrast, plasma triglyceride was reduced in SGLT2 inhibitor treated patients by 0.02-0.16 mmol/l, corresponding to a relative decrease of 1.5-11.0%. No significant treatment-associated changes in the ratio of LDL to HDL cholesterol were observed [24,26]. The results were similar in a cohort restricted to those of East Asian ancestry [26].…”

“…For instance, five meta-analyses have included between 15 and 48 RCTs of SGLT2 inhibitor treatment versus placebo and have evaluated between 4485 and 22 537 type 2 diabetes patients (Table 2) [22][23][24][25][26]. These studies found that SGLT2 inhibitor treatment was associated with significant increases in total, LDL and HDL cholesterol ranging, respectively, from 0.02 to 0.15, from 0.07 to 0.12, and from 0.05 to 0.10 mmol/l [22][23][24][25][26]. In terms of percentage changes from baseline, the ranges of increases in total, LDL and HDL cholesterol corresponded to 0.4-3.0, 2.3-4.0 and 5.0-9.0%, respectively.…”

A literature review and meta-analysis of safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus

“…For example, recent randomized controlled trials (RCTs), which included approximately 80% Caucasians, showed favorable effects on glycemic control and weight loss as well as in Asians 4 – 6 . Furthermore, meta-analyses recently showed that the effects of SGLT2 inhibitors on not only glycemic control and weight loss, but also lipid profiles were similar between Asian and non-Asian patients 7 , 8 .…”