Metformin shows its magic again!

Gastric cancer is the fifth most common malignant tumor in the world and the fourth most fatal tumor.
The most common histological type is adenocarcinoma
.

In the past more than a century, Helicobacter pylori infection has begun to attract attention, food storage and preservation technology has continued to advance, and the concept of healthy diet has gradually become popular.
The incidence and mortality of gastric cancer have shown a slow decline in most countries around the world[1 ]
.

At present, the clinical treatment of gastric adenocarcinoma is based on surgery.
For patients who cannot be operated or have metastases, chemotherapy, immunotherapy, targeted therapy, etc.
can be selected according to specific conditions
.

But even in developed countries in Northern Europe like Sweden, the 5-year survival rate of gastric adenocarcinoma patients has not increased significantly in the past few decades [2]
.

In order to explore new ways to improve the curative effect of gastric adenocarcinoma, the Shao-Hua Xie research team of Karolinska Institute in Sweden set their sights on the "first generation drug" metformin, and found that among patients with gastric adenocarcinoma and diabetes, there is a history of taking metformin.
The 5-year survival rate of patients is nearly twice that of those who do not take metformin! The research paper was published in the British Journal of Cancer [3]
.

Previous studies have found that metformin can improve the prognosis of patients with colon cancer [4] and prostate cancer [5].
A number of basic studies have also confirmed that metformin can inhibit the proliferation and metastasis of gastric cancer cells
.

However, in clinical research, because of the exposure factor of “taking metformin”, there are many confounding factors such as the time of taking medication, dosage, and the severity of diabetes.
In addition, there are differences in the ethnic characteristics of the study population.
It is much more difficult to determine whether metformin can improve the prognosis of gastric cancer.
The conclusions of the studies are not consistent[6-11]
.

The researchers searched the Swedish Prescription Drugs and Health Cohort (SPREDH) and included 1,140 diabetic patients diagnosed with gastric adenocarcinoma between July 1, 2005 and December 31, 2018, of which 777 had a history of taking metformin (taking group ), 363 people have never taken metformin (not taking group)
.

All patients were followed up from the date of diagnosis of gastric adenocarcinoma until death or the end of the study on December 31, 2019
.

The main outcome of the study was the death rate due to gastric adenocarcinoma, and the secondary outcome was all-cause mortality
.

The data showed that the 5-year survival rate of patients in the taking group was 18.
3%, while the 5-year survival rate in the non-taking group was only 9.
4%
.

In addition, the Kaplan-Meier survival curve of the two groups of patients was compared with the non-taking group.
The gastric adenocarcinoma and all-cause mortality of the taking group were lower, and the adjusted hazard ratios (HR) were 0.
79 and 0.
78, respectively
.

In addition, women, advanced tumors and less comorbidities may be protective factors, and the dose of metformin is not significantly associated with the death rate of gastric adenocarcinoma
.

Competitive risk model compared the cumulative gastric cancer mortality and all-cause mortality of the two groups of patients.
After the analysis of other fatal factors other than gastric adenocarcinoma, the risk ratio of death from gastric adenocarcinoma in the taking group compared with the non-taking group rose slightly to 0.
86 (95 % Confidence interval: 0.
73-1.
02); the risk of death due to gastric adenocarcinoma and other factors in the taking group is still lower than that of the non-taking group
.

The researchers also further controlled for confounding factors such as the severity of diabetes and the duration of the disease, and took into account that some gastric cancers may be misdiagnosed as esophageal cancer.
The analysis conclusions are consistent with those before correction; insulin and sulfonylurea drugs also have Hypoglycemic effect, but they do not have the same prognostic improvement effect as metformin
.

The SPREDH used in this study collected health data from four national registers of drugs, patients, tumors, and causes of death [12], effectively reducing the loss of follow-up and refusal to follow-up that may be caused by traditional telephone, questionnaire follow-up and other methods.
Enhance the reliability of the data, and it is also the clinical research with the largest sample size in related fields so far
.

Researchers have widely considered a variety of confounding factors and fully proved that compared with patients who have not taken metformin, patients who have taken metformin before the diagnosis of gastric adenocarcinoma have a lower risk of death and all-cause death from gastric adenocarcinoma, and The dosage taken is irrelevant, and other hypoglycemic drugs do not have similar effects
.

This study only included diabetic patients and eliminated the influence of diabetes as a confounding factor on the death risk of patients with gastric adenocarcinoma
.

However, it is worth noting that the 5-year survival rate of Swedish gastric adenocarcinoma patients has been stable at about 18% for many years [2], which is close to the data in the metformin group in this study
.

Whether metformin only offsets the adverse effects of diabetes on the prognosis of gastric adenocarcinoma and whether the effect of improving survival can be extended to the general population still needs to be tested by large-sample cohort studies and even randomized controlled trials
.

In addition, insulin and sulfonylurea drugs do not affect the prognosis, indicating that the mechanism by which metformin improves patient survival may not be limited to hypoglycemic
.

Previous studies have found that metformin can regulate the metabolism of stem cells in the stomach and promote their differentiation into gastric parietal cells with acid secretion ability, thereby playing a role in protecting the stomach and even preventing cancer [13]
.

Further exploration of the principle of metformin to improve prognosis in basic research will help truly effective drugs benefit mankind as soon as possible
.

The mechanism by which metformin regulates anti-tumor immunity (picture source: Acta Pharmacologica Sinica) At the same time, we cannot ignore the biological differences of the same tumor between eastern and western countries
.

A 2019 study in China included 543 gastric cancer patients, and finally found that whether taking metformin was not associated with gastric cancer survival [11]
.

Researchers at Zhongnan Hospital of Wuhan University are conducting a phase II clinical trial to study the effect of metformin combined with vitamin C on the prognosis of a variety of malignant tumors including gastric cancer [14], which may provide us with new evidence
.

This study alone is optimistic about the prospects of metformin in the treatment of gastric cancer.
I am afraid it is too early.
Readers are advised not to try blindly
.

However, science is progressing through continuous experimentation and exploration.
Perhaps in the near future, with more research evidence, we can see the emergence of new drugs in the guidelines, bringing hope to mankind
.

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006[14] https://clinicaltrials.
gov/ct2 /show/NCT04033107 Source of head picture: Pixabay Editor | Tan Shuo