Autoimmunity

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/iaut20

Metformin reduces autoimmune antibody levels in

patients with Hashimoto’s thyroiditis: A systematic
review and meta-analysis

Xi Jia , Tianyu Zhai & Jin-an Zhang

To cite this article: Xi Jia , Tianyu Zhai & Jin-an Zhang (2020): Metformin reduces autoimmune
antibody levels in patients with Hashimoto’s thyroiditis: A systematic review and meta-analysis,
Autoimmunity, DOI: 10.1080/08916934.2020.1789969

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AUTOIMMUNITY
https://doi.org/10.1080/08916934.2020.1789969

ORIGINAL ARTICLE

Metformin reduces autoimmune antibody levels in patients with Hashimoto’s

thyroiditis: A systematic review and meta-analysis
Xi Jiaa, Tianyu Zhaib and Jin-an Zhangc
a
Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China; bDepartment of Endocrinology and Metabolism,
Zhongshan Hospital of Fudan University, Shanghai, China; cDepartment of Endocrinology, Shanghai University of Medicine & Health
Sciences Affiliated Zhoupu Hospital, Shanghai, China

ABSTRACT ARTICLE HISTORY

Background: In the past few years, an increasing number of studies have proposed the idea of extend- Received 8 January 2020
ing the therapeutic range of metformin from traditional hypoglycaemic to autoimmune diseases, and Revised 21 May 2020
confirmed in a variety of autoimmune diseases. However, whether metformin can be used to treat Accepted 18 June 2020
Hashimoto’s thyroiditis (HT), which is characterised by thyroid peroxidase antibody (TPOAb) and thyro-
KEYWORDS
globulin antibody (TgAb), is unknown. Therefore, we conducted a systematic review and meta-analysis Metformin; TPOAb; TgAb;
to evaluate whether metformin can reduce the levels of TPOAb and TgAb in patients with HT or subclin- Hashimoto’s thyroiditis;
ical hypothyroidism (SH), so as to provide a theoretical basis for metformin treatment of these diseases. subclinical hypothyroidism
Methods: PubMed, Web Of Science and Embase were searched for observational studies investigating
the changes of TPOAb and TgAb in patients with HT after metformin treatment. Two authors extracted
data from eligible studies and classified them as HT and subclinical hypothyroidism subgroups. The
calculation was then performed by weighted mean difference (WMD) combined with a fixed-effects
model analysis or standard mean difference (SMD) with a random-effects model analysis, based on the
measurement of the outcome.
Results: Metformin significantly reduced TPOAb levels and TgAb levels in patients with HT and SH,
especially TPOAb (HT: pTPOAb ¼ .009, pTgAb ¼ .046; SH: pTPOAb ¼ .034, pTgAb ¼ .066). In addition, met-
formin also reduced the levels of thyroid stimulating hormone (TSH), homeostasis model assessment
of insulin resistance (HOMA-IR) in patients with HT and SH (HT: pTSH ¼ .000 and pHOMA-IR ¼ .000; SH:
pTSH ¼ .000 and pHOMA-IR ¼ .000, respectively).
Conclusion: Metformin significantly reduces TPOAb level and TgAb level in patients with HT and SH,
especially TPOAb. This study is the first to provide a preliminary theoretical basis for the clinical appli-
cation of metformin in the treatment of HT.

1. Introduction the thyroid gland. TPOAb and TgAb bind to complement

Hashimoto’s thyroiditis (HT) is the most common organ-spe-
cific autoimmune disease that often occurs in young people with
genetic susceptibility, especially in females [1]. HT is the most
common cause of hypothyroidism and subclinical hypothyroid-
ism (SH) in areas with adequate dietary iodine in the world [2].
HT is the result of a complex interaction between genetic sus-
ceptibility, immune and environmental factors, many of which
are yet to be determined. Among them, autoantibody produc-
tion and T cell-mediated autoimmune response play the key
pathological roles [3].
It is now established that thyroid peroxidase antibody
(TPOAb) and thyroglobulin antibody (TgAb) are the most
characteristic autoimmune antibodies to HT. Circulating
TPOAb, which is currently considered to be the best sero-
logical marker for the diagnosis of HT, is found in approxi-
mately 95% of HT patients [1,4]. TgAb is less sensitive and
specific than TPOAb, but it is the most abundant protein in
and damage thyroid cells, which contributes remarkably to
the pathogenesis of HT [1]. The pathogenic effects of these
two antibodies make their titre a sign that reflects the clin-
ical activity of the disease.
Metformin, the most widely prescribed oral hypoglycaemic
drug, has been considered as a worldwide milestone in the
treatment of type 2 diabetes for decades. In recent years, scien-
tists have also confirmed its role in heart and kidney protection,
anti-proliferation, anti-fibrosis and anti-oxidation [5]. In add-
ition, emerging evidence in vivo and in vitro supports the new
hypothesis that metformin has immunomodulatory properties
[6]. Studies have shown that metformin interferes with multiple
immunopathological mechanisms involved in autoimmune dis-
eases such as Th 17/Treg cell balance, autoantibody production,
macrophage polarisation, and cytokine synthesis [5,7]. These
provide a strong theoretical basis for applying metformin as a
candidate agent for clinical trials involving patients with auto-
immune diseases. In fact, scientists have tried to use metformin

CONTACT Jin-an Zhang zhangjinan@hotmail.com Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu
Hospital, No. 1500 Zhouyuan Road, Shanghai, 201318, China
Supplemental data for this article can be accessed here.
ß 2020 Informa UK Limited, trading as Taylor & Francis Group
2 X. JIA ET AL.
to treat autoimmune disorders and found that it can effectively
treat systemic lupus erythematosus (SLE), inflammatory bowel
disease (IBD), rheumatoid arthritis (RA) and multiple sclerosis
(MS) in animal models and in human trials [8–11]. In some
studies, it has been shown that metformin can reduce the pro-
duction of pathogenic antibodies in SLE, such as anti-nuclear
antibodies and anti-double-stranded DNA [12]. The molecular
mechanism of metformin decreasing pathogenic antibodies is
related to the increased activation of adenosine monophosphate-
activated protein kinase (AMPK) and subsequent decrease of
phosphorylation of mTOR and STAT3 [13].
TPOAb and TgAb, as important pathologic features, play
the most critical role in the diagnosis and clinical activity of
HT. In the currently known treatment of HT, the main treat-
ment is exogenous thyroid hormone supplementation, which
does not effectively and safely reduce the production of TPOAb
and TgAb, and therefore does not fundamentally treat HT.
Currently, scientists have only discovered a small number of
drugs, such as selenium and pentoxifylline, which have the abil-
ity to reduce autoimmune antibodies in HT patients, and there
is no evidence to support a wide range of clinical applications
[13–16]. Our study aimed to investigate whether metformin
can reduce the pathogenic antibodies TPOAb and TgAb in HT
patients, thus providing evidence for the possibility of metfor-
min as a therapeutic molecule for HT.
2. Methods
2.1. Search strategy
Pubmed, Embase and Web of Science were searched for
observational studies evaluating the relationship between
metformin and TPOAb or TgAb. The search keyword used
in the present study was as follows: (TSH or thyrotropin or
hypothyroidism or hyperthyroidism or thyroid or TgAb or
TPOAb or thyroid-stimulating hormone or thyroid peroxid-
ase antibodies or thyroid peroxidase antibody or thyro-
globulin antibodies or thyroglobulin antibody or thyroiditis
or Graves’ disease or hashimoto’s thyroiditis) and metfor-
min. The deadline for literature retrieval was April 10 2020,
and no language or ethnic restrictions were made.
2.2. Selection criteria
Qualified research must meet the following inclusion crite-
ria: (1) randomised controlled trials or observational studies
based on human patients including cohort studies or case-
control studies; (2) Clearly stated diagnosis of HT and SH;
(3) metformin treatment received for at least 3 months.
2.3. Data extraction
Data on sample size, characteristics of participants, metformin
dosage, length of follow-up and statistic outcomes were inde-
pendently extracted by two authors from those eligible studies
based on a predesigned form. When disagreements arose, the
final inclusion of the data was determined by a discussion
among all the authors.
2.4. Quality assessment
We evaluated the quality of the included studies according to
the Newcastle Ottawa Scale (NOS). The risk of bias involving
research was assessed primarily in three areas: the choice of
participants, the comparability between exposed and unex-
posed participants, and the determination of outcomes. Four,
two and three points were scored for each of the three
domains. Studies with a total score of < 6 were considered
to have a high risk of bias. Studies with 6 or higher scores
were considered to have a low risk of bias.
2.5. Statistical methods
Statistical analysis of changes in pre-/post-treatment with met-
formin was conducted using Stata software STATA 12.0
(StataCorp, College Station, Texas, USA). Since this study
mainly included the studies of continuous variables with the
same unit of measurement, we chose weighted mean difference
(WMD) combined with a fixed-effects model for analysis and
presented the results in forest maps. p < .05 indicated statistic-
ally different. Heterogeneity was assessed using I2 statistic and p
values of heterogeneity. When I2 > 50% and pheterogeneity <.05,
meta-regression analysis was performed to examine the poten-
tial source of heterogeneity. Interference indicators included in
the meta-regression analysis included follow-up time, sample
size, mean age, females %, smokers %, BMI, SBP, DBP and
study quality. The risk of publication bias was judged by evalu-
ating the asymmetry of the funnel plot and further verified
using Egger’s test. Sensitivity analysis was performed to deter-
mine the impact of individual studies. In this analysis, the meta-
analysis was calculated after omitting a study.
3. Results
3.1. Literature search and study selection
The details of the research selection in this meta-analysis were
shown in Figure 1. According to the above search strategy, we
retrieved a total of 798 records from the three databases.
Among the records found in the original literature search, 693
clearly unrelated records or overlapping studies were excluded
after we read the abstract and title of the study. Then, 96 full-
text publications were searched for detailed evaluation, and 92
studies were further eliminated. Of the 92 excluded studies, 9
were excluded for the lack of data on results of interest while 83
were irrelevant studies. Therefore, 4 studies were eventually
considered eligible and included in the meta-analysis (Figure 1).
3.2. Study characteristics
A total of four observational studies were included in the study
[17–20]. Since subgroups were set up in some of the studies and
their data results were presented in subgroups rather than in all
subjects, we included their subgroups as independent studies in
our meta-analysis. In the end, we obtained seven independent
observational studies. The main features of these observational
studies included in the meta-analysis are summarised in Table 1.
These studies were published between 2015 and 2018 and were
 AUTOIMMUNITY 3

Figure 1. Flow diagram of study selection in the meta-analysis.

Table 1. Characteristics of studies included into the meta-analysis.

Mean
Study ID Sample size age [years; Smokers BMI [kg/m2; SBP [mmHg; DBP [mmHg;
(subgroup) [n; (F/M)] HT (n) SH (n) mean (SD)] (%) mean (SD)] mean (SD)] mean (SD)] Other confounding factors Quality
Study 1(18) 21(21/0) 21 11 39(4) 29 29.4 (2.9) 132 (8) 87 (5) Waist; Diabetes; Impaired glucose 8
tolerance, Fasting glucose;
Estimated glomerular filtration rate;
Bromocriptine-treated (5–7.5 mg daily)
Study 2(18) 18(18/0) 18 10 40(4) 28 28.8 (3.0) 130 (10) 85 (7) Waist, Diabetes/impaired glucose 8
tolerance, Fasting glucose; Estimated
glomerular filtration rate; Cabergoline-
treated (0.5–1.0 mg weekly)
Study 3(19) 12(0/12) 8 12 48(5) 25 28.8 (2.5) 132 (14) 87 (6) Prediabetes; Diabetes; Fasting glucose 9
Study 4(19) 23(23/0) 16 23 50(6) 30 27.8 (2.6) 129 (12) 85 (5) Prediabetes; Diabetes; Fasting glucose 9
Study 5(20) 8(8/0) 0 8 43(6) 38 27.6 (3.5) 132 (8) 85 (5) Diabetes; Hepatitis C; Interferon-induced 7
Thyroiditis; Ribavirin-treated
(800–1200 mg daily)
Study 6(20) 12(12/0) 12 12 45(7) 42 28.0 (3.1) 130 (7) 85 (4) Diabetes 8
Study 7(21) 24(22/2) Not reported 24 43(14) Not reported 26.9 (4.4) 129 (15) 83 (8) Total cholesterol; TG triglycerides 9
BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure.

followed up for 3–6 months. The 7 studies involved a total of
118 metformin-treated patients, of whom 100 were diagnosed
with SH (the other 18 had high-normal thyrotropin levels) and
75 were clearly diagnosed with HT. All the studies we included
clearly indicated the gender and mean age of the subjects and
showed the proportion of smokers. Moreover, all the studies
show body mass index (BMI), systolic blood pressure (SBP)
and diastolic blood pressure (DBP). Other interference fac-
tors are also summarised in Table 1. We conducted detailed
statistics of each subgroup, and the outcomes of interest
after treatment with metformin are summarised in Table 2.
3.3. Metformin and thyroid autoimmunity
We conducted a meta-analysis of these seven studies and
divided them into two subgroups of SH patients and HT
patients. In terms of autoimmune antibodies, we found
that metformin significantly reduced the level of TPOAb,
which was more pronounced in the HT group than in the
SH group. Patients with HT showed a significant reduc-
tion in TPOAb level after receiving metformin (WMD ¼
177.61 [95%CIs 43.48–311.75]; p ¼ .009; I2 ¼ 0%), as pre-
sented in Figure 2(A) and Table 3. In patients with SH,
metformin also significantly reduced the level of TPOAb
(SMD ¼ 0.30 [95%CIs 0.02–0.58]; p ¼ .034; I2 ¼ 0%)
(Figure 2(B)). For TgAb level, only the HT group had a
significant decrease (WMD ¼ 137.06 [95%CIs 2.71–271.41];
p ¼ .046; I2 ¼ 0%), while the SH group showed only a critic-
ally positive P value (WMD ¼ 114.35 [95%CIs 7.65–236.34];
p ¼ .066; I2 ¼ 0%) (Figure 3).
In addition to antibodies, metformin also significantly
reduced TSH levels, both in the HT group and in the SH
4 X. JIA ET AL.

Table 2. Outcomes after metformin treatment.

Metformin TPOAb [U/mL; mean (SD)] TgAb [U/mL; mean (SD)] TSH [mIU/L; mean (SD)] HOMA-IR [mean (SD)] (<2.0)
dose
Study ID [g daily; follow-up After After After After
(subgroup) range] (months) Baseline treatment Baseline treatment Baseline treatment Baseline treatment
Study 1 (HT) 1.7–2.55 6 1480 (490) 1282 (514) 1390 (523) 1204 (581) 6.4 (1.8) 4.9 (1.5) 5.1 (1.0) 3.6 (0.8)
Study 1 (SH) 1.7–2.55 6 1751 (503) 1523 (491) 1512 (615) 1291 (468) 8.7 (0.6) 6.5 (1.0) 5.4 (1.2) 3.7 (1.0)
Study 2 (HT) 1.7–2.55 6 1350 (530) 1095 (380) 1275 (582) 1020 (462) 6.2 (1.6) 6.0 (1.9) 4.1 (0.8) 2.0 (0.5)
Study 2 (SH) 1.7–2.55 6 1605 (588) 1302 (470) 1405 (603) 1152 (549) 8.2 (0.7) 7.7 (0.6) 4.2 (1.0) 1.8 (0.6)
Study 3 (SH 1.7-3.0 4 893 (304) 729 (286) 782 (286) 657 (240) 7.3 (1.4) 6.9 (1.9) 5.2 (1.1) 3.2 (0.8)
and HT)
Sduty 4 (SH 1.7-3.0 4 948 (406) 802 (320) 855 (386) 780 (352) 7.5 (1.6) 5.0 (2.0) 4.8 (1.0) 3.0 (0.7)
and HT)
Study 5 (SH) 2.55–3 4 1255 (460) 1195 (394) 1218 (432) 1150 (375) 7.9 (1.1) 5.2 (1.3) 7.1 (1.4) 3.5 (1.1)
Study 6 (SH 2.55–3 4 1520 (510) 1410 (495) 1425 (487) 1328 (406) 7.8 (1.0) 6.5 (1.1) 6.8 (1.1) 4.7 (1.0)
and HT)
Study 7 (SH) 1.7 3 100 (141)a 98 (171)a Not Not 7.55 (2.2) 6.48 (3.1) 1.55 (0.9) 1.32 (0.9)
reported reported
a:U/L.

group (HT: WMD ¼ 1.25 [95%CIs 0.76–1.74]; p ¼ .000; I2
¼ 51.9%); SH: WMD ¼ 1.40 [95%CIs 1.07–1.73]; p ¼ .000;
I2 ¼ 76.9%, respectively) (Figure 4). Significant heterogen-
eity was noted in the TSH analysis of the HT and SH sub-
groups (I2 ¼ 51.9%, pHeterogeneity ¼ .000 and I2 ¼ 76.9%,
pHeterogeneity ¼ .000, respectively). Meta-regression analysis
found that follow-up time, sample size, mean age, females%,
smokers%, BMI, SBP, DBP and study quality were not the
main sources of heterogeneity (p > .05).
3.4. Metformin and HOMA-IR
Meta-analysis of those studies suggested that treatment with
metformin significantly reduced the level of HOMA-IR.
This reduction effect was significant in both the HT and SH
groups (HT: WMD ¼ 1.89 [95%CIs 1.62–2.16]; p ¼ .000; I2
¼ 0%; SH: WMD ¼ 1.61 [95%CIs 1.35–1.88]; p ¼ 000; I2 ¼
86.3%), and the detailed results are shown in Figure 5 and
Table 3.
3.6. Publication bias and sensitivity analysis
The shape of the funnel plot did not indicate a significant
asymmetry tendency, indicating a low risk of publication
bias (Supplementary Figure S1). In addition, the p values of
all egger tests in the present study were greater than .05,
further indicating that there was no publication bias (Table
3). Sensitivity analysis was performed for each analysis in
the present study. The final results showed that no single
study had a significant impact on the overall meta-analysis.
None of the results changed following the sensitivity ana-
lysis. The result is shown in Supplementary Figure S2.
4. Discussion
In the past few decades, the versatile effect of metformin
has been well proven. The role of metformin in the immune
system and its potential in the treatment of autoimmune
diseases is one of the hotspots of current research. Scientists
have been trying to use it to treat various autoimmune
diseases in animals and humans, such as SLE, RA, IBD and
MS [8–11]. However, its role in autoimmune thyroiditis has
not been studied. On this basis, we conducted this study
and proved for the first time that metformin can signifi-
cantly reduce the characteristic autoimmune antibodies
TPOAb and TgAb of HT and SH, and reduce TSH levels.
This provides potential possibility and theoretical basis for
metformin treatment of HT.
Hashimoto’s thyroiditis (HT) is a common autoimmune
disease characterised by high levels thyroid peroxidase
antibody (TPOAb), and thyroid globulin antibody (TgAb),
accompanying weakened thyroid function or not. Primary
hypothyroidism is common in 5% of individuals and more
commonly diagnosed in women. Mild hypothyroidism
occurs in 15% of the elderly [21]. Subclinical hypothyroid-
ism is defined as elevated serum thyroid stimulating hor-
mone levels, but serum levels of free thyroxine and free
triiodothyronine are within the reference range [22]. SH
can be caused by a variety of factors, including dietary iod-
ine deficiency, genetic predispositions and some agents
include stavudine and thalidomide, where HT is the most
common cause [22]. HT is a condition of altered T cell-
mediated immunity leading to destruction of thyroid tissue
and impaired glandular function, characterised by lympho-
cytic infiltration and fibrosis. Although glandular inflam-
mation is primarily a result of T cell-mediated functional
changes, circulating anti-thyroid antibodies against thyroid
peroxidase and thyroglobulin are markers of the disease and
play a significant crucial role in the diagnosis, identification,
and guidance of treatment [23]. The levels of TPOAb and
TgAb are commonly used as indicators of HT disease activity,
of which TPOAb is the most important indicator. Our results
found that metformin can significantly reduce the levels of
TPOAb and TgAb, and is more effective than TgAb in reduc-
ing TPOAb. In fact, at present, there are very few drugs that
can clinically reduce the level of autoantibodies in patients
with HT [16,24]. The metformin’s safety and benefits to other
systems also provide convenience for its clinical use in the
treatment of HT. Therefore, our findings is of great signifi-
cance for the development of new drugs for the treatment.
 AUTOIMMUNITY 5

Figure 2. Meta-analysis of eligible studies showed that TPOAb was significantly decreased after metformin treatment. A: In the HT group; B: In the SH group.

In fact, studies in which metformin reduces pathogenic
antibodies have been demonstrated in SLE disease. Metformin
has been shown to be effective in reducing anti-nuclear
antibodies, anti-double-stranded DNA antibodies and anti-
mtDNA autoantibodies in animal models of SLE [9,12,25].
In contrast, metformin can increase the protective antibody
response. Diaz et al. [26] evaluated the antibody response
to influenza vaccination in naïve T2D patients and those
on metformin treatment. It was found that metformin
enhanced vaccine-specific antibody titres both in vivo and
in vitro, and this effect was accompanied by increased
memory B cells and decreased late/depleted B cells. The
6 X. JIA ET AL.

Table 3. Summary of the main findings in the meta-analysis.

pHeterogeneity I2 for pegger test
Analysis participants p Values WMD (95%CI) Values heterogeneity (%) Values (95%CI)
HT patients 75
TPOAb .009 177.61(43.48–311.75) 0.978 0.0 0.81(4.17–3.54)
TgAb .046 137.06(2.71–271.41) 0.936 0.0 0.30(2.47–5.71)
TSH .000 1.25(0.76–1.74) 0.081 51.9 0.77(12.11–9.88)
HOMA-IR .000 1.89(1.62–2.16) 0.522 0.0 1.00(5.51–5.51)
SH patients 100
TPOAb .034 0.30(0.02–0.58)a 0.910 0.0 0.34(1.66–3.98)
TgAb .066 114.35(7.65–236.34) 0.983 0.0 0.22(0.56–1.73)
TSH .000 1.40(1.07–1.73) 0.000 76.9 0.53(4.87–8.31)
HOMA-IR .000 1.61(1.35–1.88) 0.000 86.3 0.11(2.02–13.74)
a:SMD(95%CI).

Figure 3. Meta-analysis of eligible studies showed that TgAb was significantly decreased after metformin treatment.

study of metformin on antibody-producing B cells has also
made a breakthrough in recent years. Studies have shown that
deletion of mTOR genes significantly reduces B cell prolifer-
ation and germinal centre (GC) formation in autoimmune
diseases [27]. Metformin activates AMPK phosphorylation,
inhibits mTOR activity, and thereby inhibits B cell activity,
which is also associated with the inhibition of TNF-a, miR-
155, and miR-16 expression by metformin [25].
In addition to autoimmune antibodies TPOAb and TgAb,
HT also has the characteristics of hypothyroidism and high
serum TSH levels. It is now appreciated that although hypothy-
roidism or subclinical hypothyroidism is not a necessary clin-
ical manifestation of HT patients, hypothyroidism and high
TSH levels are still the most common manifestations of HT.
Interestingly, scientists from multiple laboratories have found
that metformin has the property of lowering serum TSH levels
and is limited to people with clinical or subclinical hypothy-
roidism [28,29]. When metformin is discontinued, TSH level
increases again [30,31]. However, metformin has no significant
effect on thyroxine (T4) or triiodothyronine (T3). The

Figure 4. Meta-analysis of eligible studies showed that TSH was significantly decreased after metformin treatment.
hypothetical mechanisms of this effect are: sensitisation of thy-
roid hormone receptors, regulation of type II deiodinase activ-
ity at the hypothalamic-pituitary level, and regulation of
dopaminergic tone on TSH secretion. There is a hypothesis
that metformin alters the sensitivity and/or quantity of thy-
roid hormone receptors [31]. In addition, it can cross the
blood-brain barrier, increase central dopaminergic tone,
induce TSH receptor activation, and regulate hypothalamic-
pituitary type II deiodinase activity, thereby enhancing the
role of thyroid hormone in the pituitary and inhibiting TSH.
In addition, the TSH reduction of metformin may be caused
by metformin-induced activation of AMPK, which involves
a variety of cellular functions and regulates cellular energy
metabolism. Furthermore, unlike the periphery, metformin
has been shown to have an inhibitory effect on AMPK activ-
ity in the hypothalamus.
Another finding in this study was that metformin reduced
HOMA-IR level in patients with HT and SH. In fact, studies
have reported that insulin resistance is one of the risk fac-
tors for hypothyroidism. Dessein et al. [32] explored this
issue specifically for SH patients with rheumatoid arthritis.
Studies have shown that mild hypothyroidism is associated
with insulin resistance, even after controlling for disturbances
AUTOIMMUNITY 7
such as BMI and disease-related inflammation. Other stud-
ies have also found that HOMA-IR and fasting insulin lev-
els are higher in the SH or HT patients than in the control
group [33–37]. In addition, other studies have shown that
SH patients have higher serum insulin levels than the con-
trol group, although there is no significant positive P value
in the HOMA index [38,39]. Our study shows that metfor-
min can significantly reduce HOMA-IR level in SH patients
and HT patients. This demonstrates from another perspec-
tive that metformin may have a therapeutic effect on HT
and SH.
Overall, our study found for the first time that metfor-
min can reduce autoimmune antibody levels in patients
with SH and HT, especially TPOAb. This is important in
guiding metformin for the treatment of HT. In addition,
we also found that metformin can reduce TSH level and
HOMA-IR level in patients with SH and HT. However, our
research still has a lot of deficiencies. Observational studies
with longer follow-up time can help get a more comprehen-
sive and accurate results. Researches based on more regions
and ethnic groups can also help us perform better statistical
analysis to assess the effect of metformin in reducing auto-
immune antibody levels in patients with HT and SH.
8 X. JIA ET AL.
Figure 5. Meta-analysis of eligible studies showed that HOMA-IR was significantly decreased after metformin treatment.
Acknowledgments
We thank all the authors for participating in this study.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
The present work was supported by grants from the National Natural
Science Foundation of China [No. 81873636].
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