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▎Metformin, editor of WuXi AppTec's content team, is a classic first-line drug for the treatment of type 2 diabetes.
In addition to the role of classic hypoglycemic drugs, the potential health effects of metformin in other disease fields have always been concerned.
We have previously introduced its research in lung cancer, breast cancer, Alzheimer's disease and other diseases.
There have been a number of interesting studies published this year.
We share these new academic developments of metformin with readers.
Common breast cancer risk reduction studies published in the Annals of Oncology found that the development of type 2 diabetes and breast cancer may vary depending on the subtype (hormone receptor status) of breast cancer.
In this study, most women with type 2 diabetes took metformin, which may help reduce the risk of estrogen receptor (ER)-positive breast cancer.
The study recruited 44,541 women aged 35-74 who had not previously been diagnosed with breast cancer.
After an average follow-up of 8.
6 years, it was found that 2678 cases of breast cancer were diagnosed at least 1 year after enrollment.
3227 women had type 2 diabetes, 2389 women had type 2 diabetes newly, 61% of them (n = 3386) had received metformin treatment.
There was no overall correlation between type 2 diabetes and breast cancer risk (HR 0.
99), but the risk of triple-negative breast cancer (TNBC) increased by 40% (HR 1.
40).
Compared with patients without type 2 diabetes, women with type 2 diabetes taking metformin had a 14% lower risk of ER-positive breast cancer (HR 0.
86), a 25% higher risk of ER-negative breast cancer (HR 1.
25), and a 74% higher risk of TNBC ( HR 1.
74).
Neither ER-positive nor ER-negative breast cancer risk changes were statistically significant.
Long-term (≥10 years) taking metformin will reduce the risk of ER-positive breast cancer more significantly, reducing it by 38% (HR 0.
62).
The mechanisms by which metformin may reduce the risk of breast cancer include: improving insulin sensitivity and correcting high insulin levels by reducing the amount of insulin and insulin-like growth factors circulating in the body.
High insulin levels may activate cell signals involved in cancer; metformin may also By activating adenylate activated protein kinase (AMPK) to slow down the growth of breast cancer, because AMPK can inhibit the pathway involved in the proliferation of cancer cells; metformin may also inhibit the estrogen receptor that plays a role in the occurrence and development of breast cancer, thereby reducing ER The risk of positive breast cancer.
The researchers concluded: "These findings indicate that having type 2 diabetes may increase the risk of breast cancer, but taking metformin may prevent the development of ER-positive breast cancer, which is the most common type of breast cancer.
Metformin appears to be ER-negative or Triple-negative breast cancer has no protective effect.
We cannot determine whether the increased risk of TNBC is due to metformin's failure to protect or because metformin itself may cause the risk of TNBC.
"Image source: 123RF inhibits HIV replication in cells according to the latest WHO It is estimated that approximately 38 million people worldwide are infected with HIV.
At present, doctors use combined antiretroviral therapy (ART) to inhibit HIV replication, but many patients still show signs of residual virus replication and immune damage.
And even patients who respond well to ART drugs must take the drug for a long time, because HIV copies itself into the DNA of some infected cells, and the drug cannot clear the virus' genes.
Previous studies have found that when HIV infects CD4 T immune cells, it can promote the oxidative phosphorylation of CD4 cells, thereby enhancing the ability of the virus to replicate in cells.
This study, published in Nature Immunology, confirmed through experiments carried out in human CD4 cells and mice with human CD4 cells that metformin can inhibit the oxidative phosphorylation of CD4 cells, thereby inhibiting HIV in the cells Copy.
In addition, analyzing the data of HIV patients receiving ART treatment, the researchers also found that after 6 months of treatment, compared with non-diabetic patients, patients with type 2 diabetes (many may be taking metformin) had HIV levels in the blood.
An average reduction of 33%.
On average, patients with diabetes have higher baseline CD4 cell levels, and CD4 cell levels recover faster after antiretroviral therapy.
The co-first author of the study, Dr.
HaitaoGuo, assistant professor in the Department of Genetics at the UNC School of Medicine, said: "This finding suggests that metformin and other drugs that reduce T cell metabolism may be used as adjuvant therapies for the treatment of HIV.
" Another option for reducing chronic inflammation in HIV-infected patients Studies have found that metformin can also help HIV-infected people who are receiving anti-ART treatment to reduce chronic inflammation.
Although ART can help improve the health of HIV-infected individuals, seropositive individuals are at higher risk of chronic inflammation-related complications (such as cardiovascular disease).
These health problems are mainly due to the continuous existence of the HIV virus reservoir in the patient's memory T cells and the continuous activation of their immune system.
The corresponding author of the study and Professor of Immunology at the University of Montreal (Université de Montréal) Petronela Ancuta said: “We already know that metformin interferes with the activity of the mTOR (mammalian target of rapamycin) molecule, which is involved in the cells of the HIV genome.
Internal proliferation.
The size of the HIV virus pool is related to the level of inflammation.
Previous studies have shown that inhibiting mTOR with drugs can significantly inhibit the replication of HIV in the cells of patients infected with the virus, thereby reducing chronic inflammation.
"Researchers treated with metformin 22 A non-diabetic HIV-infected person receiving antiretroviral therapy found that the patient tolerated the drug extremely well.
Moreover, the researchers observed the beneficial biological effects of metformin in colon biopsy.
It was found that the activation of mTOR in CD4 T cells present in the colon was reduced, and certain plasma markers of inflammation and intestinal injury were reduced.
Therefore, metformin has intestinal and systemic effects.
Image source: 123RF relieves pre-eclampsia of premature birth.
A study published at the 2021 pregnancy conference of the Society for Maternal-Fetal Medicine (SMFM) showed that metformin prolonged in pregnant women with preeclampsia (Preeclampsia).
Nearly a week of pregnancy is also related to the shortening of the newborn’s hospital stay.
Pre-eclampsia refers to symptoms such as high blood pressure, proteinuria, headache, vertigo, nausea, vomiting, and upper abdominal discomfort during pregnancy.
In women with normal blood pressure, pre-eclampsia usually starts after 20 weeks of pregnancy.
The trial recruited a total of 180 women with pre-eclampsia at 26-31 weeks of pregnancy, all of whom were taking antihypertensive drugs.
The researchers randomly assigned subjects to take 3g of metformin or placebo orally every day.
Of these, 87 received metformin and 84 received a placebo.
The baseline characteristics of the two groups were similar.
After adjusting for compliance and dosage, the study showed that among 147 women who continued treatment until delivery, the median delivery time of the metformin group was 8.
4 days later than that of the placebo group (16.
2 vs 7.
4 days, P=0.
026).
Further analysis of 100 women who continued to take full dose metformin until delivery revealed that the median delivery time in the metformin group was 11.
4 days later than the placebo group (16.
2 vs 4.
8 days, P=0.
008).
In addition, the average total hospital stay of infants in the metformin group was 26 days, while the average total hospital stay of infants in the placebo group was 34 days (P=0.
007).
But compared with women taking placebo, women taking metformin may experience diarrhea and nausea.
Cathy Cluver, a professor at Stellenbosch University in Cape Town, South Africa, said: “Metformin may be a drug for the treatment of pre-eclampsia of premature birth.
We plan to conduct a larger study and hope to confirm these findings in order to prolong pregnancy and improve pregnancy.
The neonatal outcome provides a plan. Professor Michelle Y.
Owens, director of maternal and child medicine at the University of Mississippi Medical Center, said: “The sample size of this study is small and the dose exceeds the dose normally used in the United States.
Moreover, the population of the study is in South Africa, and its applicability to other populations in the world is reduced.
In addition, the use of metformin to extend pregnancy may affect birth weight because it helps control blood sugar and may reduce birth weight in the future compared with women who are not taking the drug.
"Improve the symptoms of tuberous sclerosis.
A study published in the "Lancet" sub-Journal EBio Medicine found that metformin can successfully reduce the symptoms of tuberous sclerosis (TSC), including reducing the frequency of seizures and the size of brain tumors.
.
the TSC is a genetic disorder characterized by the growth is due to the inhibitory regulation of the mTOR pathway and benign cell loss occurs.
Thus, people suffering from the disease may hamartomas (hamartomas) will occur in the body, affecting the heart , Kidneys, brain, skin, and possibly disfigurement or even life-threatening complications.
Because tumors can form in the brain, 75% of TSC patients will suffer from epilepsy, leading to daily seizures.
The
researchers recruited 51 people.
Patients with TSC were randomly assigned to placebo or metformin for 1 year, with a dose similar to that of type 2 diabetes.
Among them, 27 patients had subependymal giant cell astrocytoma (SEGA), and 21 of them received epileptic seizures.
Frequency assessment.
The
research team found that people who took metformin had a 21% reduction in brain tumor volume within one year, while those who took a placebo had a 3% increase in tumor volume.
Patients who took metformin had a 44% reduction in seizure frequency, compared with comfort The dose group dropped by only 3%.
University College London (University College London) professor of pediatric neuroscience Finbar O'Callaghan said: "We have found that metformin is more effective in treating young TSC patients.
Patients who had seizures several times a day or multiple times a week had no seizures after 12 months of treatment, while other patients also had fewer seizures than before.
Next, further large-scale trials will be conducted in TSC patients to determine the optimal dose and effect of metformin.
"Related reading What are the effects of metformin on lung cancer survival? The International Agency for Research on Cancer has participated in large-scale studies to accumulate new evidence after tracking 1,000 elderly people for many years and found that metformin may prevent dementia? JTO 700,000 data: aspirin, metformin and statins, all reduced Lung cancer risk, eating together is more effective? Make triple-negative breast cancer cells more likely to "see the light and die".
Metformin combined with oxygen photodynamics has initial therapeutic potential "The Lancet": Comparing heart and kidney benefits, first-line treatment of type 2 diabetes, Has the status of metformin been impacted? Reference materials (slide up and down to view) [1] Lohmann, AE, & Goodwin, PJ (2021).
Diabetes, metformin and breast cancer: a tangled web.
Annals of Oncology, 32(3), 285-286.
[2] Park, YM, Bookwalter, DB, O'Brien, KM, Jackson, CL, Weinberg, CR, & Sandler, DP (2021).
A prospective study of type 2 diabetes, metformin use, and risk of breast cancer.
Annals of Oncology, 32(3), 351-359.
[3] Guo, H.
, Wang, Q.
, Ghneim, K.
, Wang, L.
, Rampanelli, E.
, Holley-Guthrie, E .
, .
.
.
& Ting, JPY (2021).
Multi-omics analyses reveal that HIV-1 alters CD4+ T cell immunometabolism to fuel virus replication.
Nature Immunology, 1-11.
[4] HIV:An antidiabetic drug to reduce chronic inflammation.
Retrieved MARCH 18, 2021, from https://medicalxpress.
com/news/2021-03-hiv-antidiabetic-drug-chronic-inflammation.
html[5] Metformin may affect risk of breast cancer in women with type 2 diabetes.
Retrieved 28-JAN-2021, from https:// Metformin Tied to Longer Gestation in Women With Preterm Preeclampsia.
Retrieved February 01, 2021, from https:// Metformin trial dramatically reduces seizures in tuberous sclerosis.
Retrieved MARCH 29, 2021, from https://medicalxpress.
com/news/2021 -03-metformin-trial-seizures-tuberous-sclerosis.
html[8] Diabetes drug may be a new weapon against HIV.
Retrieved MARCH 29, 2021, from https://medicalxpress.
com/news/2021-03-diabetes- drug-weapon-hiv.
html Note: This article aims to introduce the progress of medical and health research, not a treatment plan recommendation. If you need guidance on treatment plans, please go to a regular hospital for treatment.
In addition to the role of classic hypoglycemic drugs, the potential health effects of metformin in other disease fields have always been concerned.
We have previously introduced its research in lung cancer, breast cancer, Alzheimer's disease and other diseases.
There have been a number of interesting studies published this year.
We share these new academic developments of metformin with readers.
Common breast cancer risk reduction studies published in the Annals of Oncology found that the development of type 2 diabetes and breast cancer may vary depending on the subtype (hormone receptor status) of breast cancer.
In this study, most women with type 2 diabetes took metformin, which may help reduce the risk of estrogen receptor (ER)-positive breast cancer.
The study recruited 44,541 women aged 35-74 who had not previously been diagnosed with breast cancer.
After an average follow-up of 8.
6 years, it was found that 2678 cases of breast cancer were diagnosed at least 1 year after enrollment.
3227 women had type 2 diabetes, 2389 women had type 2 diabetes newly, 61% of them (n = 3386) had received metformin treatment.
There was no overall correlation between type 2 diabetes and breast cancer risk (HR 0.
99), but the risk of triple-negative breast cancer (TNBC) increased by 40% (HR 1.
40).
Compared with patients without type 2 diabetes, women with type 2 diabetes taking metformin had a 14% lower risk of ER-positive breast cancer (HR 0.
86), a 25% higher risk of ER-negative breast cancer (HR 1.
25), and a 74% higher risk of TNBC ( HR 1.
74).
Neither ER-positive nor ER-negative breast cancer risk changes were statistically significant.
Long-term (≥10 years) taking metformin will reduce the risk of ER-positive breast cancer more significantly, reducing it by 38% (HR 0.
62).
The mechanisms by which metformin may reduce the risk of breast cancer include: improving insulin sensitivity and correcting high insulin levels by reducing the amount of insulin and insulin-like growth factors circulating in the body.
High insulin levels may activate cell signals involved in cancer; metformin may also By activating adenylate activated protein kinase (AMPK) to slow down the growth of breast cancer, because AMPK can inhibit the pathway involved in the proliferation of cancer cells; metformin may also inhibit the estrogen receptor that plays a role in the occurrence and development of breast cancer, thereby reducing ER The risk of positive breast cancer.
The researchers concluded: "These findings indicate that having type 2 diabetes may increase the risk of breast cancer, but taking metformin may prevent the development of ER-positive breast cancer, which is the most common type of breast cancer.
Metformin appears to be ER-negative or Triple-negative breast cancer has no protective effect.
We cannot determine whether the increased risk of TNBC is due to metformin's failure to protect or because metformin itself may cause the risk of TNBC.
"Image source: 123RF inhibits HIV replication in cells according to the latest WHO It is estimated that approximately 38 million people worldwide are infected with HIV.
At present, doctors use combined antiretroviral therapy (ART) to inhibit HIV replication, but many patients still show signs of residual virus replication and immune damage.
And even patients who respond well to ART drugs must take the drug for a long time, because HIV copies itself into the DNA of some infected cells, and the drug cannot clear the virus' genes.
Previous studies have found that when HIV infects CD4 T immune cells, it can promote the oxidative phosphorylation of CD4 cells, thereby enhancing the ability of the virus to replicate in cells.
This study, published in Nature Immunology, confirmed through experiments carried out in human CD4 cells and mice with human CD4 cells that metformin can inhibit the oxidative phosphorylation of CD4 cells, thereby inhibiting HIV in the cells Copy.
In addition, analyzing the data of HIV patients receiving ART treatment, the researchers also found that after 6 months of treatment, compared with non-diabetic patients, patients with type 2 diabetes (many may be taking metformin) had HIV levels in the blood.
An average reduction of 33%.
On average, patients with diabetes have higher baseline CD4 cell levels, and CD4 cell levels recover faster after antiretroviral therapy.
The co-first author of the study, Dr.
HaitaoGuo, assistant professor in the Department of Genetics at the UNC School of Medicine, said: "This finding suggests that metformin and other drugs that reduce T cell metabolism may be used as adjuvant therapies for the treatment of HIV.
" Another option for reducing chronic inflammation in HIV-infected patients Studies have found that metformin can also help HIV-infected people who are receiving anti-ART treatment to reduce chronic inflammation.
Although ART can help improve the health of HIV-infected individuals, seropositive individuals are at higher risk of chronic inflammation-related complications (such as cardiovascular disease).
These health problems are mainly due to the continuous existence of the HIV virus reservoir in the patient's memory T cells and the continuous activation of their immune system.
The corresponding author of the study and Professor of Immunology at the University of Montreal (Université de Montréal) Petronela Ancuta said: “We already know that metformin interferes with the activity of the mTOR (mammalian target of rapamycin) molecule, which is involved in the cells of the HIV genome.
Internal proliferation.
The size of the HIV virus pool is related to the level of inflammation.
Previous studies have shown that inhibiting mTOR with drugs can significantly inhibit the replication of HIV in the cells of patients infected with the virus, thereby reducing chronic inflammation.
"Researchers treated with metformin 22 A non-diabetic HIV-infected person receiving antiretroviral therapy found that the patient tolerated the drug extremely well.
Moreover, the researchers observed the beneficial biological effects of metformin in colon biopsy.
It was found that the activation of mTOR in CD4 T cells present in the colon was reduced, and certain plasma markers of inflammation and intestinal injury were reduced.
Therefore, metformin has intestinal and systemic effects.
Image source: 123RF relieves pre-eclampsia of premature birth.
A study published at the 2021 pregnancy conference of the Society for Maternal-Fetal Medicine (SMFM) showed that metformin prolonged in pregnant women with preeclampsia (Preeclampsia).
Nearly a week of pregnancy is also related to the shortening of the newborn’s hospital stay.
Pre-eclampsia refers to symptoms such as high blood pressure, proteinuria, headache, vertigo, nausea, vomiting, and upper abdominal discomfort during pregnancy.
In women with normal blood pressure, pre-eclampsia usually starts after 20 weeks of pregnancy.
The trial recruited a total of 180 women with pre-eclampsia at 26-31 weeks of pregnancy, all of whom were taking antihypertensive drugs.
The researchers randomly assigned subjects to take 3g of metformin or placebo orally every day.
Of these, 87 received metformin and 84 received a placebo.
The baseline characteristics of the two groups were similar.
After adjusting for compliance and dosage, the study showed that among 147 women who continued treatment until delivery, the median delivery time of the metformin group was 8.
4 days later than that of the placebo group (16.
2 vs 7.
4 days, P=0.
026).
Further analysis of 100 women who continued to take full dose metformin until delivery revealed that the median delivery time in the metformin group was 11.
4 days later than the placebo group (16.
2 vs 4.
8 days, P=0.
008).
In addition, the average total hospital stay of infants in the metformin group was 26 days, while the average total hospital stay of infants in the placebo group was 34 days (P=0.
007).
But compared with women taking placebo, women taking metformin may experience diarrhea and nausea.
Cathy Cluver, a professor at Stellenbosch University in Cape Town, South Africa, said: “Metformin may be a drug for the treatment of pre-eclampsia of premature birth.
We plan to conduct a larger study and hope to confirm these findings in order to prolong pregnancy and improve pregnancy.
The neonatal outcome provides a plan. Professor Michelle Y.
Owens, director of maternal and child medicine at the University of Mississippi Medical Center, said: “The sample size of this study is small and the dose exceeds the dose normally used in the United States.
Moreover, the population of the study is in South Africa, and its applicability to other populations in the world is reduced.
In addition, the use of metformin to extend pregnancy may affect birth weight because it helps control blood sugar and may reduce birth weight in the future compared with women who are not taking the drug.
"Improve the symptoms of tuberous sclerosis.
A study published in the "Lancet" sub-Journal EBio Medicine found that metformin can successfully reduce the symptoms of tuberous sclerosis (TSC), including reducing the frequency of seizures and the size of brain tumors.
.
the TSC is a genetic disorder characterized by the growth is due to the inhibitory regulation of the mTOR pathway and benign cell loss occurs.
Thus, people suffering from the disease may hamartomas (hamartomas) will occur in the body, affecting the heart , Kidneys, brain, skin, and possibly disfigurement or even life-threatening complications.
Because tumors can form in the brain, 75% of TSC patients will suffer from epilepsy, leading to daily seizures.
The
researchers recruited 51 people.
Patients with TSC were randomly assigned to placebo or metformin for 1 year, with a dose similar to that of type 2 diabetes.
Among them, 27 patients had subependymal giant cell astrocytoma (SEGA), and 21 of them received epileptic seizures.
Frequency assessment.
The
research team found that people who took metformin had a 21% reduction in brain tumor volume within one year, while those who took a placebo had a 3% increase in tumor volume.
Patients who took metformin had a 44% reduction in seizure frequency, compared with comfort The dose group dropped by only 3%.
University College London (University College London) professor of pediatric neuroscience Finbar O'Callaghan said: "We have found that metformin is more effective in treating young TSC patients.
Patients who had seizures several times a day or multiple times a week had no seizures after 12 months of treatment, while other patients also had fewer seizures than before.
Next, further large-scale trials will be conducted in TSC patients to determine the optimal dose and effect of metformin.
"Related reading What are the effects of metformin on lung cancer survival? The International Agency for Research on Cancer has participated in large-scale studies to accumulate new evidence after tracking 1,000 elderly people for many years and found that metformin may prevent dementia? JTO 700,000 data: aspirin, metformin and statins, all reduced Lung cancer risk, eating together is more effective? Make triple-negative breast cancer cells more likely to "see the light and die".
Metformin combined with oxygen photodynamics has initial therapeutic potential "The Lancet": Comparing heart and kidney benefits, first-line treatment of type 2 diabetes, Has the status of metformin been impacted? Reference materials (slide up and down to view) [1] Lohmann, AE, & Goodwin, PJ (2021).
Diabetes, metformin and breast cancer: a tangled web.
Annals of Oncology, 32(3), 285-286.
[2] Park, YM, Bookwalter, DB, O'Brien, KM, Jackson, CL, Weinberg, CR, & Sandler, DP (2021).
A prospective study of type 2 diabetes, metformin use, and risk of breast cancer.
Annals of Oncology, 32(3), 351-359.
[3] Guo, H.
, Wang, Q.
, Ghneim, K.
, Wang, L.
, Rampanelli, E.
, Holley-Guthrie, E .
, .
.
.
& Ting, JPY (2021).
Multi-omics analyses reveal that HIV-1 alters CD4+ T cell immunometabolism to fuel virus replication.
Nature Immunology, 1-11.
[4] HIV:An antidiabetic drug to reduce chronic inflammation.
Retrieved MARCH 18, 2021, from https://medicalxpress.
com/news/2021-03-hiv-antidiabetic-drug-chronic-inflammation.
html[5] Metformin may affect risk of breast cancer in women with type 2 diabetes.
Retrieved 28-JAN-2021, from https:// Metformin Tied to Longer Gestation in Women With Preterm Preeclampsia.
Retrieved February 01, 2021, from https:// Metformin trial dramatically reduces seizures in tuberous sclerosis.
Retrieved MARCH 29, 2021, from https://medicalxpress.
com/news/2021 -03-metformin-trial-seizures-tuberous-sclerosis.
html[8] Diabetes drug may be a new weapon against HIV.
Retrieved MARCH 29, 2021, from https://medicalxpress.
com/news/2021-03-diabetes- drug-weapon-hiv.
html Note: This article aims to introduce the progress of medical and health research, not a treatment plan recommendation. If you need guidance on treatment plans, please go to a regular hospital for treatment.
