Where is the "god" effect of the hypoglycemic drug metformin on rheumatism?

*Only for medical professionals to read for reference, the points are different~ As we all know, the classic drugs for the treatment of rheumatism are non-steroidal anti-inflammatory drugs, traditional synthetic anti-rheumatic drugs, biological agents, etc.
, but more and more studies have found Some classic drugs in non-rheumatic fields are actually beneficial to rheumatism
.

Among them is the well-known hypoglycemic drug metformin
.

Reduce blood sugar, "anti-cancer", slow down aging.
.
.
Metformin has been used in the treatment of diabetes for decades since it was discovered in the extract of caprosine in the 1920s, and it is currently used to treat type 2 diabetes.
Of the first-line oral therapy
.

There are many reports on the molecular mechanism of metformin.
The most important molecular mechanism is to regulate the activity and function of downstream proteins by activating AMP-activated protein kinase (AMPK) [1]
.

In recent years, the "old drug and new use" of metformin has attracted the attention of many scholars.
Some retrospective studies including epidemiological studies have shown that metformin can benefit many cancer patients; Nature has reported on the mechanism of metformin in cancer.
It is believed to be closely related to the inhibition of mitochondrial glycerophosphate dehydrogenase
.

Published in 2013, a study in the Cell magazine showed that metformin slowed the aging process by mimicking the dieting effect
.

A study by the United States Diabetes Prevention Program (DPP) research team showed that in an unblinded study period of 7-8 years, patients who received metformin treatment lost an average of 3.
1 kg in weight
.

Metformin's various "spiritual effects" once amazed the world, what is it that it can't do! So, does metformin have certain benefits for rheumatism? Research on the effect of metformin on rheumatism is in full swing.
Globally, the prevalence and incidence of autoimmune diseases are increasing year by year.
With the continuous update of disease diagnosis and treatment methods, the therapeutic effect of autoimmune diseases has been improved globally
.

Although more and more evidence shows that such diseases are related to genetic and environmental factors, so far, the pathological mechanism of autoimmune diseases and the pharmacological mechanism of related drugs have not been fully clarified
.

At the same time, new drugs and treatment options need to be explored to improve the treatment effect of such diseases
.

The potential application of metformin in the treatment of several rheumatic diseases is worthy of attention
.

1.
Rheumatoid arthritis (RA): Metformin can affect the neutrophil extracellular bactericidal network (NETs), M2 type macrophages, The expression of rheumatoid factor (RF) subgroups can simultaneously play a role in bone protection and regulate the effects of intestinal microbes to achieve RA remission, which may open up a new clinical treatment perspective for RA; and has the advantages of fewer adverse reactions and low cost, which is expected Become one of the more ideal treatment drugs for RA
.

2.
Systemic lupus erythematosus (SLE): SLE has a complicated pathogenesis.
Glucocorticoids are still the key drugs for treatment, and hormone-induced infections are still the main cause of death in SLE patients.
A study [2] showed that The addition of metformin to the treatment of SLE can reduce the recurrence rate of the patient's disease, reduce hormone exposure and lower body mass index (BMI), improve the metabolic syndrome of the patient, and maintain the stability of the disease in SLE patients
.

Another study [3] further found that metformin has the potential to reduce infection events in SLE patients
.

3.
Osteoarthritis (OA): OA is a common exercise systemic disease in the elderly.
The pathogenesis of this disease is not yet clear.
There are no specific drugs for the treatment of this disease, mainly through glucosamine and non-steroidal anti-inflammatory.
Drugs, hyaluronic acid injection and other programs are used to relieve the pain of patients, delay the degeneration of articular cartilage, and improve the quality of life
.

In recent years, clinical applications have found that metformin has a good intervention effect on the bone density of diabetic patients, can stimulate the differentiation of bone formation, reduce bone loss, and promote bone repair
.

Another study used a mouse model of traumatic OA to prove that metformin has a protective effect on OA
.

4.
Sjogren’s syndrome: Primary Sjogren’s syndrome (pSS) is an autoimmune disease in which inflammatory cells infiltrate the secretory glands of the human body.
The clinical features are mainly dry mouth, dry eyes, lumps of teeth, and glands.
The manifestations of external involvement, including arthritis, skin rash, interstitial pneumonia, peripheral neuropathy, etc.
, are pathologically characterized by lymphocyte infiltration
.

The influence of T cell subgroups on the disease has attracted more and more attention.
It is believed that certain environmental factors stimulate and activate the initial CD4+ T cells of individuals with genetic susceptibility, stimulate them to differentiate into different inflammatory cells, and destroy the body’s immune stability.
State, leading to an uncontrollable inflammatory response
.

Initial CD4+ T lymphocytes can differentiate into helper T cells (Th, such as Th1, Th2, Th17) and Treg cells
.

A large number of studies have shown that the expression level of T cell subsets in the peripheral blood of pSS patients is different from that of healthy people, especially Treg cells
.

Metformin can increase the number of Treg cells in patients with Sjogren’s syndrome, regulate the balance of Th17/Treg cells and return to normal erythrocyte sedimentation rate
.

5.
Gout: Gout is an inherited inflammatory metabolic disorder characterized by repeated acute arthritis and uric acid deposition around the joints
.

A global survey on gout showed that the disability-adjusted life years of gout patients increased from 76,000 in 1990 to 114,000 in 2010
.

This evidence shows that the diagnosis and treatment of gout is not effective in most parts of the world, and there is an urgent need for a newer and better diagnosis and treatment plan for gout
.

The use of metformin is safe for patients with gout.
A report [4] pointed out that metformin has the effects of reducing insulin resistance, lowering uric acid and alleviating joint syndrome
.

The results of a clinical trial involving 30 patients showed that [5] after 12 months of using metformin, the patients' blood uric acid, insulin levels and insulin resistance decreased significantly
.

Researchers speculate that metformin reduces the formation of uric acid by inhibiting the biosynthesis of free fatty acids
.

6.
Behcet’s disease: The pathogenesis of Behcet’s disease has many similarities with type 2 diabetes.
For example, inflammation of the pancreatic islets leads to an increase in IL-1β levels, which leads to a decline in β-cell function.
It is found in Behcet’s disease.
The same mechanism
.

Similarly, Treg/Th17 balance disorders are found in both type 2 diabetes and Behcet's disease
.

The up-regulated TNF-α level is also the common pathogenesis of these two diseases
.

A study found that metformin can reduce the recurrence rate of skin and mucosal lesions of Behcet's disease, reduce active erythrocyte sedimentation rate and C-reactive protein, suggesting that metformin may be one of the alternative drugs for the treatment of Behcet's disease [6]
.

Summary: Although the study of metformin involves many fields, a large sample of repeated studies is still needed to further observe the long-term efficacy
.

References: [1]Graham Rena,D.
Grahame Hardie,Ewan R.
Pearson,et al.
The mechanisms of action of metformin[J].
Diabetologia.
2017;60(9):1577–1585.
[2]Wang H ,Li T,Chen S,et al.
Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof-ofconcept trial of metformin[J].
Arthritis Rheumatol,2015,67(12):3190-3200.
[3 ] Geng Shikai, Zhang Le, Wang Huijing, et al.
Exploring the effect of metformin in reducing infections in patients with systemic lupus erythematosus: post-hoc analysis of a Met-Lupus study [J].
Journal of Shanghai Jiaotong University, 2021
.

[4]VG Barskova,MS Eliseev,EL Nasonov,et al.
Use of metformin(siofor)in patients with gout and insulin resistance(pilot 6-month results)[J].
Ter Arkh,2005,77(12):44 -49[5]VG Barskova,MS Eliseev,FM Kudaeva,et al.
Effect of metformin on the clinical course of gout and insulin resistance[J].
Klin Med(Mosk).
2009;87(7):41-6.
[6]Chen Yong, Luo Dan, Zou Jun, et al.
Prospective clinical study of metformin intervention in mucocutaneous Behcet's disease[J].
Journal of Jinan University (Natural Science and Medicine Edition), 2016, 37(5).
Source of this article : Rheumatism and Immunity Channel of the Medical Circle Author of this article: Volume Review of this article: Chen Xinpeng, Deputy Chief Physician Editor: Cassette Copyright Statement The timeliness of the published content, as well as the accuracy and completeness of the quoted materials (if any), etc.
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.

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.