Received: 10 April 2019 Revised: 28 August 2019 Accepted: 11 February 2020

DOI: 10.1002/pds.4985

ORIGINAL REPORT

Effects of sodium glucose cotransporter 2 inhibitors on risk

of dyslipidemia among patients with type 2 diabetes:
A systematic review and meta-analysis of randomized
controlled trials

Dandan Li1 | Tingxi Wu1 | Tiansheng Wang2 | Hongtao Wei1 | Aihua Wang3 |
Huilin Tang4 | Yiqing Song4

1
Department of Pharmacy, Beijing Friendship
Hospital, Capital Medical University, Beijing, Abstract
China Purpose: Sodium glucose cotransporter 2 (SGLT2) inhibitors are shown to cause small,
2
Department of Epidemiology, Gillings School
but significant changes of lipid profiles, we aim to investigate whether such altered
of Global Public Health, University of North
Carolina at Chapel Hill, Chapel Hill, North lipid profiles can be translated into clinically meaningful changes in dyslipidemia.
Carolina
Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials
3
Department of Pharmacy, Beijing Obstetrics
and Gynecology Hospital, Capital Medical (CENTRAL) were searched for randomized controlled trials (RCTs) that compared
University, Beijing, China SGLT2 inhibitors with placebo or other oral glucose-lowering drugs in patients with
4
Department of Epidemiology, Richard
type 2 diabetes mellitus and reported the events of dyslipidemia. A random-effect
M. Fairbanks School of Public Health, Indiana
University, Indianapolis, Indiana, USA meta-analysis was performed to calculate the pooled estimates with risk ratio
(RR) for dyslipidemia risk and weighted mean difference for lipid profiles with their
Correspondence
Yiqing Song and Huilin Tang, Department of 95% confidential intervals (CIs).
Epidemiology, Richard M. Fairbanks School of
Results: Of 2427 studies identified, 15 RCTs involving 7578 patients were included.
Public Health, Indiana University, 1050
Wishard Blvd, Indianapolis, IN 46202, USA. This meta-analysis found no association between SGLT2 inhibitors and risk of dys-
Email: yiqsong@iu.edu (Y. S.) and
lipidemia (RR: 1.13; 95% CI: 0.91-1.40). However, SGLT2 inhibitors were significantly
huiltang@iu.edu (H. T.)
associated with increases in total cholesterol by 0.15 mmol/L, low-density lipoprotein
cholesterol by 0.12 mmol/L, and high-density lipoprotein cholesterol by 0.07 mmol/L
while they can significantly decrease triglycerides by −0.12 mmol/L compared to
controls.
Conclusions: SGLT2 inhibitors were not associated with increased risk of dys-
lipidemia. Further trials with longitudinal assessment are needed to assess the effect
of SGLT2 inhibitors on trajectories of changes of lipid metabolism.

KEYWORDS

dyslipidemia, meta-analysis, pharmacoepidemiology, SGLT2 inhibitors, type 2 diabetes

1 | I N T RO DU CT I O N decreased doses of insulin without increasing hypoglycemia owing to

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of
oral glucose-lowering drugs for type 2 diabetes mellitus (T2DM) by
1
reducing glucose reabsorption through kidney. They are reported to
be associated with additional benefits such as weight loss and
their insulin-independent mechanism of action.1,2 Furthermore, cumu-
lative evidence has indicated that they can achieve favorable cardio-
vascular outcomes compared to control drugs.3
However, it has been reported that SGLT2 inhibitors are asso-
ciated with increases in low-density lipoprotein cholesterol (LDL-

Pharmacoepidemiol Drug Saf. 2020;1–9. wileyonlinelibrary.com/journal/pds © 2020 John Wiley & Sons Ltd 1
2 LI ET AL.

C),4 which seemed to be contradictory to the cardiovascular bene-

fits. Dyslipidemia, which refers to altered, most often excessive, Key points
concentration of lipids in blood and manifests as hypercholesterol-
1. Current evidence has shown that sodium glucose
emia, hypertriglyceridemia, or mixed forms (Medical Dictionary for
cotransporter 2 (SGLT2) inhibitors might influence blood
Regulatory Activities [MedDRA, version 21.0]), is a primary risk
lipid profiles; however, whether such changes could
factor for atherosclerotic cardiovascular disease (ASCVD) and con-
affect the risk of clinically diagnosed dyslipidemia remain
tributes to the increased risk for coronary artery disease and
unclear.
stroke.5,6
2. Our meta-analysis of 15 randomized trials involving
However, it remains unclear whether the changes in lipid profiles
7578 patients with type 2 diabetes showed no signifi-
by SGLT2 inhibitors could be translated into a discernable increased
cant effects of SGLT2 inhibitors on risk of dyslipidemia.
risk of clinically diagnosed dyslipidemia. We therefore conducted this
3. Our meta-analysis found that SGLT2 inhibitors were sig-
systematic review and meta-analysis of randomized controlled trials
nificantly associated with increased levels of total cho-
(RCTs) to explore the metabolic effect of SGLT2 inhibitors on the risk
lesterol, low-density lipoprotein cholesterol, and high-
of newly dyslipidemia and fasting lipid profiles, including LDL-C, high-
density lipoprotein cholesterol, but a decrease in
density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and tri-
triglycerides.
glycerides (TG).

2 | MATERIALS AND METHODS comprehensively from inception to 20 March 2018 to identify trials
that compared SGLT2 inhibitors with placebo or other oral glucose-
2.1 | Data source and searches lowering drugs in patients with T2DM using predefined search strat-
egies (Table S1). ClinicalTrials.gov and references of included trials
Electronic databases including PubMed, Embase, and Cochrane Cen- and relevant meta-analysis were also screened for additional eligible
tral Register of Controlled Trials (CENTRAL) were searched trials.

FIGURE 1 Flowchart of study

selection
 LI ET AL.

TABLE 1 Baseline characteristics of included RCTs and participants

Duration Mean Mean Total LDL HDL

Sample Background Race of diabetes HbA1c BMI cholesterol Triglycerides cholesterol cholesterol Definitions of Follow-upa
Authors NCT SGLT2 inhibitors Controls size (n) therapy (Primary) (years) (%) (kg/m2) (mmol/L) (mmol/L) (mmol/L) (mmol/L) dyslipidemia (weeks)

Bailey et al7 NCT00528879 DAPA5mg;10 mg PLA 409 MET White 6.1 8.10 31.5 4.8 2.2 2.7 1.1 MedDRA 13.0 102

Henry et al8 NCT00643851 DAPA 5 mg PLA 395 MET White 1.6 9.2 NR NR NR NR NR MedDRA 12.0 24

Henry et al8 NCT00859898 DAPA 10 mg PLA 419 MET White 2.1 9.1 NR NR NR NR NR MedDRA 13.0 24

Strojek NCT00680745 DAPA5mg;10 mg PLA 442 SU (GLI) White 7.4 8.1 29.8 5.0 2.1 2.8 1.2 MedDRA 12.1 48
et al9

Rosenstock NCT00683878 DAPA: PLA 420 PIOG White 5.49 8.4 NA NR NR NR NR MedDRA 12.1 48
et al10 5 mg;10 mg

Ji et al11 NCT01095653 DAPA: PLA 393 Naïve Asian 1.4 8.3 25.6 4.9 2.3 2.8 1.2 MedDRA 15.0 24
5 mg;10 mg treatment
Yang et al12 NCT01095666 DAPA: PLA 444 MET Asian 4.9 8.1 26.1 NR NR NR NR MedDRA 16.0 24
5 mg;10 mg

Yang et al13 NCT02096705 DAPA:10 mg PLA 272 Insulin Asian 12.5 8.5 26.5 NR NR NR NR MedDRA 18.1 24

Ridderstrale NCT01167881 EMPA: 25 mg SU(GLI) 1545 MET White NR 7.9 30.1 4.5 1.9 2.4 1.3 MedDRA 15.0 104
et al14

Lewin NCT01422876 EMPA: 10 mg; LINA 5 mg 405 Naïve White NR 8.0 31.5 5.0 2.1 2.9 1.2 MedDRA 16.0 52
et al15 25 mg treatment

Kovacs NCT01210001/ EMPA: 10 mg; PLA 498 PIOG±MET Asian NA 8.1 29.2 4.8 1.8 2.7 1.3 MedDRA 16.0 76
et al16 NCT01289990 25 mg

Merker NCT01159600/ EMPA: 10 mg; PLA 637 MET White NR 7.9 29.2 4.6 1.9 2.5 1.3 MedDRA 16.0 76
et al17 NCT01289990 25 mg

Roden NCT01177813/ EMPA: 10 mg; PLA AND 899 Naïve Asian NA 7.88 28.4 5.0 2.2 2.8 1.3 MedDRA 16.0 76
et al18 NCT01289990 25 mg SIT treatment

Mathieu NCT01646320 DAPA:10 mg PLA 320 SAXA+MET White 7.6 8.20 31.7 4.9 2.4 2.8 1.2 MedDRA 17.1 52
et al19
Shigiyama UMIN000018754 DAPA: 5 mg MET 80 MET Asian 5.9 6.9 26.6 5.1 1.6 2.7 1.4 NR 16
et al20

Note: This table illustrated the treatment arms and the baseline characteristics of all participants of the included studies, but only arms that compared SGLT2 inhibitors and other oral antidiabetic drugs were
included for meta-analysis.
Abbreviations: CANA, canagliflozin; DAPA, dapagliflozin; EMPA, empagliflozin; GLI, glimepiride; LINA, linagliptin; MedDRA, Medical Dictionary for Regulatory Activities.; MET, metformin; NA, data were shown,
but not in mean ± SD form; NR, not reported; PIOG, pioglitazone; PLA, placebo; RCTs, randomized controlled trials; SAXA, saxagliptin; SGLT2, sodium glucose cotransporter 2; SIT, sitagliptin; SU, sulphonylurea.
a
The follow-up duration means that of the dyslipidemia, the primary outcome.
3
4 LI ET AL.
2.2 | Study selection
Trials would be included only if they fulfill all the inclusion criteria as fol-
lows: (a) RCTs were performed in patients with T2DM, (b) participants in
the treatment group received SGLT2 inhibitors that approved worldwide,
including canagliflozin, dapagliflozin, empagliflozin, ipragliflozin,
remogliflozin, luseogliflozin, and tofogliflozin and those in control group
took placebo or other oral glucose-lowering drugs, (c) treatment duration
≥12 weeks, and (d) reported the occurrence of dyslipidemia. The primary
outcome was new cases of dyslipidemia during the trials and the second-
ary outcomes were changes of fasting lipid profiles after treatment vs
before treatment, including TC, LDL-C, HDL-C, and TG. Dyslipidemia
was identified based on the preferred items of MedDRA used in each
RCT. Two reviewers performed the study selection independently, and
disagreement was resolved by discussion with a third reviewer.
2.3 | Data extraction and quality assessment
Data extraction was performed using self-designed extraction form
including first author (publication year), study characteristics, patient
characteristics, events of dyslipidemia, and changes of fasting lipid
F I G U R E 2 Meta-analysis of the effects of SGLT2 inhibitors on risk of dyslipidemia compared to controls in patients with type 2 diabetes.
SGLT2, sodium glucose cotransporter 2
parameters (mean difference, or mean levels and their SDs/errors). If
multiple reports of the same trial were obtained during different follow-
up periods, only the one with longest follow-up was extracted, but the
fact that interested events were only reported within shorter duration.
The quality of included RCTs was assessed according to the
Cochrane risk-of-bias tool and judged to be low, unclear or high risk
of bias based on the following domains: random sequence generation
(selection bias); allocation concealment (selection bias); blinding (per-
formance bias and detection bias); incomplete outcome data (attrition
bias); and selective reporting (reporting bias). Two reviewers indepen-
dently conducted the data extraction and quality assessment. Any dis-
crepancy was resolved through discussion with a third reviewer.
2.4 | Data synthesis and analysis
All SGLT2 inhibitors of approved doses were deemed as treatment
group including 5 mg/10 mg dapagliflozin and 10 mg/25 mg
empagliflozin, and the control group included placebo and/or all the
other oral glucose-lowering drugs.
To further explore potential effect modifications on the relation-
ship between SGLT2 inhibitors and risk of dyslipidemia, subgroup
LI ET AL.
analysis and random-effect meta-regression were performed by strati-
fying to types of SGLT2 inhibitor, different doses of SGLT2 inhibitor,
follow-up durations (<52 vs ≥52 weeks), baseline body mass index
(BMI, ≥30 vs <30 kg/m2), types of comparators (placebo vs other oral
glucose-lowering drugs), background treatments (naive treatments vs
glucose-lowering drugs), the primary race of included patients (White
vs Asian), risk of bias on detection bias and reporting bias (low risk vs
unclear or high risk).
SGLT2 inhibitors were stratified into high (25 mg empagliflozin and
10 mg dapagliflozin) and low doses (10 mg empagliflozin and 5 mg
dapagliflozin). Changes of fasting lipid profiles were shown as mmol/L, and
unit conversion was performed as follows: 1 mg/dL ≈ 0.02586 mmol/L
for LDL-C, HDL-C, and TC; 1 mg/dL ≈ 0.01129 mmol/L for TG.
Risk ratio (RR) for dichotomous data and weighted mean differ-
ence (WMD) for continuous data with 95% confidential intervals (CIs)
were estimated using DerSimonian and Laird method with random
effects to compare the risk of dyslipidemia and fasting lipid profiles
T A B L E 2 Subgroup analysis of
Comparisons
effects of SGLT2 inhibitors on risk of
dyslipidemia in patients with type 2 Type of SGLT2 inhibitors
diabetes Dapagliflozin vs control
Empagliflozin vs control
Doses of SGLT2 inhibitors
High doses vs control
Low doses vs control
Duration of follow-up
≥52 wk
<52 wk
Baseline BMI
≥30 kg/m2
2
<30 kg/m
Types of comparators
Placebo
Other oral glucose-lowering drugs
Background treatment
Naive treatments
Glucose-lowering drugs
Primary race
White
Asian
Detection bias
Low
Unclear
Reporting bias
Low
High
Note: High doses of SGLT2 inhibitors included 10 mg dapagliflozin and 25 mg empagliflozin, low doses of
SGLT2 inhibitors included 5 mg dapagliflozin and 10 mg empagliflozin.
Abbreviations: BMI, body mass index; RR, risk ratio.
a
Results with significant difference.
5
between SGLT2 inhibitors and controls. Heterogeneity between stud-
ies was evaluated using the I2 statistic and judged to be either low
(<25%), moderate (25%-75%), or high (>75%). Begg's and Egger's tests
were used to show publication bias, and P values less than .05 indi-
cated statistically significant difference. All statistical analyses were
performed using STATA (Version 14; STATA Corp., College Station,
Texas).
3 | RE SU LT S
We have identified 2427 citations from electronic search; and after
title, abstract as well as full text screening, 15 RCTs involving 7578
patients met the inclusion criteria and finally included in this study
(Figure 1). Baseline characteristics of included studies and definitions
of dyslipidemia are shown in Table 1. Involved SGLT2 inhibitors
included only dapagliflozin and empagliflozin; the mean HbA1c of
No. of trials No. of patients RR (95% CI) I2
10 3594 1.07 (0.69, 1.67) 32.8
5 3984 1.17 (0.91, 1.50) 0.0
13 5670 1.19 (0.91, 1.57) 20.8
11 3570 1.11 (0.83, 1.47) 0.0
7 4713 1.20 (0.94, 1.52) 0.0
8 2865 0.98 (0.57, 1.66) 40.6
4 2679 1.21 (0.85, 1.74) 0.0
8 3665 0.95 (0.66, 1.37) 29.4
12 5325 1.11 (0.84, 1.48) 19.1
4 2706 1.14 (0.82, 1.59) 0.0
5 2462 0.96 (0.56, 1.65) 35.0
10 5116 1.20 (0.95, 1.52) 0.0
9 4992 1.34 (1.01, 1.77)a 0.0
6 2586 0.86 (0.58, 1.27) 30.3
6 2545 0.90 (0.52, 1.54) 36.4
9 5033 1.22 (0.96, 1.55) 0.0
10 4742 1.18 (0.85, 1.64) 13.8
5 2836 1.09 (0.80, 1.49) 8.2
6 LI ET AL.

included patients ranged from 6.9% to 9.2%, and the follow-up dura-
tion varied from 16 to 104 weeks. Some RCTs reported patients'
baseline lipid profiles, which seemed similar across these studies.
The results of quality assessment are shown in Supplementary
Figure S1 (Risk-of-bias assessment of included studies). In this study,
we included all RCTs. Of them, only one study was open-label design,
and judged to be high risk of bias on performance bias. Five studies
were judged high risk of reporting bias because the data was reported
in the ClinicalTrials.gov, but not in the publications. All included RCTs
were judged high risk of other bias because they are funded by or

F I G U R E 3 Meta-analysis of the
effects of SGLT2 inhibitors on lipid
profiles. HDL-C, high-density
lipoprotein cholesterol; LDL-C, low-
density lipoprotein cholesterol;
SGLT2, sodium glucose cotransporter
2; TC, total cholesterol; TG,
triglycerides
LI ET AL.
cooperated with pharmaceutical companies. No publication bias was
identified based on Begg's and Egger's tests except for TG (Table S2).
3.1 | SGLT2 inhibitors and dyslipidemia risk
The occurrence of dyslipidemia was 5.60% (246/4394) in SGLT2
inhibitor users and 4.81% (153/3184) in the controls. Only
dapagliflozin and empagliflozin were included in this meta-analysis,
and the results showed that SGLT2 inhibitors were not significantly
associated with a higher risk of dyslipidemia (RR: 1.13; 95%CI:
0.91-1.40) than controls (Figure 2), and the RR for dapagliflozin and
empagliflozin were 1.07 (95%CI: 0.69-1.67) and 1.17 (95%CI:
0.91-1.50), respectively.
When subgroup analysis was performed, SGLT2 inhibitors were
associated with higher risk of dyslipidemia in the White (RR: 1.34;
2
95% CI: 1.01-1.77) without heterogeneity (I = 0.0%). No significant
differences were found in the other subgroup analyses (Table 2).
Univariate meta-regression with random-effect model indicated
that baseline BMI (P = .026) has significant modification effect on the
dyslipidemia (Figure S2), while none of doses of SGLT2 inhibitor
(P = .742), types of SGLT2 inhibitor (P = .653), follow-up duration
(P = .540), types of comparators (P = .379), background treatment
(P = .912), primary race (P = .101), detection bias (P = .280), or
reporting bias (P = .811) affected the association of SGLT2 inhibitors
and risk of dyslipidemia.
3.2 | SGLT2 inhibitors and fasting lipid profiles
Nine trials reported the changes of all fasting lipid profiles including
TC, LDL-C, HDL-C, and TG. Among the 5097 patients reported
changes of TC, significant difference (WMD: 0.15 mmol/L; 95%CI:
0.06-0.23 mmol/L) was found between SGLT2 inhibitors and controls
(Figure 3). Similarly, significant increases were found in LDL-C (WMD:
0.12 mmol/L; 95%CI: 0.07-0.17 mmol/L) and HDL-C (WMD:
0.07 mmol/L; 95%CI: 0.05-0.09 mmol/L) based on 5091 and 5096
participants, respectively (Figure 3). SGLT2 inhibitors were associated
with significant decrease in TG (WMD: −0.12 mmol/L; 95%CI: −0.17
to −0.06 mmol/L) with moderate heterogeneity by analyzing data
from 5106 patients (Figure 3).
4 | DISCUSSION
Our meta-analysis found that SGLT2 inhibitors were not significantly
associated with increased risk of dyslipidemia for the overall popula-
tion. However, our meta-regression indicated that higher baseline
BMI might be associated with increased risk of dyslipidemia. We
observed significant increases in TC, HDL-C, and LDL-C while
decrease in TG associated with SGLT2 inhibitors when compared to
placebo or other oral glucose-lowering drugs. The findings were in line
with our previous meta-analysis of 4828 patients in 14 RCTs
7
indicating that add-on SGLT2 inhibitors to DPP-4 inhibitors were
associated with significant increase in TC of 3.24%, HDL-C of 6.15%,
and LDL-C of 2.55%.4
In the subgroup meta-analysis, an increased risk of dyslipidemia
was observed among the White patients; however, meta-regression
did not find the modification effect. It may be explained by the fact
that higher baseline BMI was observed among the White patients
(Table 1) compared with Asian patients (Table 1). Considering the
modification effect of BMI on dyslipidemia, even though no significant
difference detected, the higher BMI (≥30 kg/m2) may be associated
with higher risk of dyslipidemia within larger sample size.
In fasted hamsters treated with empagliflozin, there was a signifi-
cant 31% increase in the activity of 3-hydroxy-3-methylglutaryl-CoA
(HMG-CoA) reductase, the key enzyme for cholesterol synthesis. At
the same time, the expression of hepatic LDL receptor protein was
reduced by 20%.21 These changes indicated the metabolic response
of SGLT2 inhibitor users shifting from carbohydrate to lipid utilization
in fasting condition22,23 because SGLT2 inhibitors inhibited renal glu-
cose reabsorption, and caused calorie loss from the urine. The
increased free fatty acids and total ketone body in animal models well
verified this hypothesis.21,24
In the meantime, increased LDL-C and reduced TG levels were
also found in mouse model expressing human cholesteryl ester trans-
fer protein and human apolipoprotein B100 (ApoB100) after inhibition
of SGLT2 by canagliflozin or a specific antisense oligonucleotide in
fasting condition.25 SGLT2 inhibition was associated with lowered
mRNA levels of both genes that expressing LDL receptors and its
posttranscriptional modulator PCSK9 in the liver as well as modest
decrease in the hepatic LDL receptor protein level, suggesting that
increased LDL-C was because of reduced clearance of LDL from the
circulation.25 Meanwhile, the decreased postprandial lipemia, an index
of blood triglyceride clearance and often viewed as an in vivo assay of
lipolytic capacity, indicating the inhibition of SGLT2 lead to greater
lipolysis of TG-rich lipoproteins.25
However, the increase of lipid profiles including TC and LDL-C
seemed to conflict with the cardio-protective effect of SGLT2 inhibi-
tors, which has been documented by several large RCTs and a previ-
ous meta-analysis.1,26 LDL-C is the most abundant cholesterol
transporter in the body and has been demonstrated to be the causa-
tive factor in ASCVD.27 Though significant difference was detected
for SGLT2 inhibitor users on LDL-C, no higher risk of dyslipidemia
was found. This suggested that metabolic changes associated with
SGLT2 inhibitors were probably not strong enough to damage the car-
diovascular system. Besides, the elevated HDL-C, which is inversely
associated with cardiovascular disease risk,28 may partly offset the
destructive effect of the increased LDL-C level. Thirdly, the metabolic
changes in the fasting condition, when the lipid tests were always per-
formed in RCTs, probably could not illustrate the overall effect of
SGLT2 inhibitors on lipid profiles, at least for SGLT2 inhibitor users.
Interestingly, even though significant increase of HMG-CoA reductase
activity and reduction of hepatic LDL receptor protein expression
were found in the fasted hamsters treated with empagliflozin, this
phenomenon not found in fed conditions of the animal model.21 On
8 LI ET AL.
the contrary, empagliflozin even reduced intestinal cholesterol absorp-
tion in vivo, which led to a significant increase excretion from fecal21
indicating different or even somewhat opposite effect of SGLT2 inhib-
itors on lipids between the fasting and nonfasting conditions. Even
though lipids were classically measured after an overnight fast, recent
studies have discussed the value of nonfast test,29,30 and the
European Atherosclerosis Society and the European Federation of
Clinical Chemistry and Laboratory Medicine concluded that tests of
nonfasting samples were at least as robust as that gained from fasting
analysis.31 Thus, tests of changes of lipid profiles in the fasting condi-
tion should be cautiously interpreted and not be used as the only clini-
cal evidence for predicting or treating cardiovascular risk among
SGLT2 inhibitor users.
This is the first meta-analysis to explore the association between
SGLT2 inhibitors and dyslipidemia. However, the major limitation of
this study is the limited number of included studies. Even though com-
prehensive search strategies were performed, there were only 15 trials
that met our inclusion criteria. Secondly, follow-up durations of
included studies varied greatly, although we found no modification
effect of duration in the meta-regression analysis. Thirdly, the hetero-
geneity among studies remained high and there was also high hetero-
geneity between trials in several subgroup analyses. One possible
reason for the heterogeneity may be the difference of lipid lowering
drug use among studies, which could not be obtained from published
reports. Results of our meta-analysis should be interpreted cautiously.
In conclusion, this meta-analysis of RCT data suggested that
SGLT2 inhibitors were not associated with higher risk of dyslipidemia,
but the risk increased with higher baseline BMI. In the meantime, sig-
nificant increase in fasting TC, HDL-C and LDL-C, and decrease in TG
were observed among SGLT2 inhibitor users. Further trials are needed
to assess the effect of SGLT2 inhibitors on dyslipidemia among obese
patients (≥30 kg/m2), and the causal effects of SGLT2 inhibitors on
trajectories of changes of lipid metabolism.
ACKNOWLEDGMENT
We thank Dr Shanshan Wu from Clinical Epidemiology and EBM Cen-
ter, Beijing Friendship Hospital, the Second Clinical Medical College of
Capital Medical University for providing support of statistical analysis.
E TH I CS S T A TE M E N T
The authors state that no ethical approval was needed.
CONF LICT OF IN TE RE ST
The authors declare no conflict of interest.
AUTHOR CONTRIBUTIONS
D.D.L. was responsible for study design, literature search, data collec-
tion, data analysis, data interpretation, drafting of the manuscript, crit-
ical revision of the manuscript, and approval of the final submission.;
T.X.W. was responsible for literature search, data collection, critical
revision of the manuscript, and approval of the final submission;
T.S.W. was responsible for study design, critical revision of the manu-
script, and approval of the final submission; H.T.W. and A.H.W. were
responsible literature search, data collection, critical revision of the
manuscript, and approval of the final submission; H.L.T was responsi-
ble for study concept and design, data interpretation, critical revision
of the manuscript, and approval of the final submission. H.L.T. and
Y.Q.S are the guarantors of this work, had full access to all the data in
the study, and take responsibility for the integrity of the data and the
accuracy of the data analysis.
OR CID
Huilin Tang https://orcid.org/0000-0002-5814-6657
Yiqing Song https://orcid.org/0000-0002-2097-7332
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SUPPORTING INF ORMATION
Additional supporting information may be found online in the
Supporting Information section at the end of this article.
How to cite this article: Li D, Wu T, Wang T, et al. Effects of
sodium glucose cotransporter 2 inhibitors on risk of
dyslipidemia among patients with type 2 diabetes: A
systematic review and meta-analysis of randomized controlled
trials. Pharmacoepidemiol Drug Saf. 2020;1–9. https://doi.org/
10.1002/pds.4985