The researchers conducted detailed examinations of cellular interactions with the metformin, studying its role in relation to HMGB1 during the progression of periodontitis. It was observed that metformin could inhibit oxidative stress and activate autophagy through AMPK/mTOR pathway. Experimental periodontitis was induced in a mouse model and metformin was found to attenuate alveolar bone resorption, a major hallmark of the disease.
Periodontitis, a widespread global health problem, causes the gradual destruction of the supporting tissues of the teeth and is often exacerbated by conditions of oxidative stress and bacterial alterations. Current treatment methodologies include mechanical debridement, anti-inflammatory drugs, and regenerative surgery.
There research was published in Genes & Diseases.
The multiple benefits of using metformin
A notable finding of this study is that metformin not only reduces oxidative stress in periodontal ligament cells, but also activates autophagy, a process of removing and recycling cellular waste, via the AMPK/mTOR pathway. This pathway has been shown to inhibit HMGB1-mediated oxidative stress in periodontal tissues.
The study concludes that metformin can mitigate periodontal tissue damage through its anti-inflammatory effects, which involve reducing the expression and translocation of HMGB1, a key proinflammatory factor. These results are in line with previous studies demonstrating metformin's ability to reduce oxidative stress. The research is published in the journal Genes & Diseases.
The critical role of HMGB1 in inducing oxidative stress in periodontal cells adds further credence to this protein being a potential target for periodontal intervention. This opens a promising avenue for future research and drug development targeting HMGB1.
“Although our study presents compelling evidence for the protective role of metformin in periodontitis, further research is needed,” the research team said. “We are optimistic that our findings will pave the way for more comprehensive studies of the relationship between metformin and HMGB1 in periodontitis, ultimately leading to more effective treatment options.”
The potential role of metformin in the management of periodontitis could be transformative, especially for patients with both diabetes and periodontitis. The study results offer hope for a cost-effective, well-tolerated and readily available treatment option, based on the known antidiabetic effects of metformin. This is in line with the broader medical goal of developing targeted treatments that manage disease symptoms while addressing the root cause.
ICU patients often suffer from diabetes mellitus (DM) along with chronic heart failure (CHF). In these patients the use of metformin in intensive care is controversial. This study aimed to evaluate the mortality rates of patients with DM and CHF treated with metformin.
The Medical Information Mart for Intensive Care database was used to identify patients with type 2 diabetes mellitus (T2DM) and CHF. A comparison of 90-day mortality was conducted between patients who received and did not receive metformin. Propensity score matching analysis and multivariable Cox proportional hazard regression were used to ensure robustness of the results.
A total of 2,153 patients (180 metformin-treated and 1,973 metformin-untreated) patients with T2DM and CHF were included in the study. The 90-day mortality rates were 30.5% (601/1,971) and 5.5% (10/182) in the non-metformin and metformin groups, respectively. In propensity score matching analyses, metformin use was associated with 71% lower 90-day mortality (hazard ratio, 0.29; 95% confidence interval, 0.14-0.59 ; P < 0.001). Results were insensitive to change when sensitivity analyzes were performed.
The researchers conclude that metformin treatment can reduce the risk of mortality in critically ill patients with T2DM and CHF in the intensive care unit.
An additional study titled “The potential benefit of metformin to reduce the risk of delirium and mortality: a retrospective cohort study” was published in Aging.
Metformin has been reported to improve age-related disorders, including dementia, and reduce mortality. This study was conducted to test whether metformin use reduces the risk of delirium and long-term mortality.
In the current retrospective cohort study, researchers from Stanford University School of Medicine, University of Iowa Carver College of Medicine, University of Iowa College of Public Health, and Tottori University School of Medicine analyzed 1,404 previously recruited subjects. The relationship between metformin use and delirium and the relationship between metformin use and 3-year mortality were studied.
The researchers say: “Therefore, in this report we aimed to investigate the relationship between DM [ diabete mellito ] and risk of delirium focusing on the influence of metformin. We hypothesized that history of metformin use is associated with a lower risk of delirium. We were also interested in testing whether anamnestic use of metformin can alter one of the most important patient outcomes, mortality.”
In total, 242 subjects were classified into a type 2 diabetes mellitus (DM) group without metformin and 264 subjects were classified into a DM with metformin group. The prevalence of delirium was 36.0% in the DM without metformin group and 29.2% in the DM with metformin group.
A history of metformin use reduced the risk of delirium in patients with DM (OR, 0.50 [IC al 95%, da 0,32 a 0,79]) after controlling for confounding factors.
The 3-year mortality in the DM group without metformin (survival rate, 0.595 [IC al 95%, da 0,512 a 0,669]) was higher than in the DM metformin group (survival rate, 0.695 [IC al 95%, 0,604 a 0,770]) (p=0.035). A history of metformin use reduced the risk of 3-year mortality after adjustment for confounders (HR, 0.69 [IC al 95%, da 0,48 a 0,98]). The researchers concluded that the use of metformin may reduce the risk of delirium and mortality in patients with DM.
“In this report, we demonstrated the potential benefit of metformin in reducing the risk of delirium and mortality in subjects with DM,” the researchers conclude.
According to another study published online in JAMA Surgery, preoperative metformin prescriptions may be associated with decreased postoperative mortality and hospital readmission among patients with diabetes undergoing major surgery.
Katherine M. Reitz, of the University of Pittsburgh School of Medicine, and colleagues used electronic health record data to identify 10,088 adults with diabetes who underwent major surgery with hospitalization (January 2010 to January 2016) in 15 community and academic hospitals. within a single healthcare system. 59% had preoperative metformin prescriptions. The analysis included 5,460 propensity score-matched patients (mean age 67.7 years; 53% women).
The researchers found that in the propensity score-matched cohort, preoperative metformin was associated with a reduced risk of 90-day mortality (hazard ratio [HR] adjusted, 0.72 [intervallo di confidenza (CI) al 95%, da 0,55 a 0,95]; absolute risk reduction [ARR]1.28% [IC 95%, da 0,26 a 2,31]) and 30-day readmission risk (ARR, 2.09% [IC 95%, da 0,35 a 3,82]; sub-HR, 0.84 [IC 95%, 0,72 a 0,98]) and 90 days (ARR, 2.78% [IC al 95%, da 0,62 a 4,95]; sub-HR, 0.86 [IC al 95%, da 0,77 a 0,97]).
Preoperative inflammation was lower in patients with a metformin prescription than in those without (mean neutrophil/leukocyte ratio, 4.5 [IC al 95%, da 4,3 a 4,6] compared to 5.0 [IC al 95%, da 4,8 a 5,3]).
“The benefits are likely not disease-specific, but the pleiotropic properties may instead modulate the stress response generated by major surgery or confer consistently good outcomes, regardless of the surgical procedure,” the authors write.
Metformin use may provide a survival benefit in subjects with post-pancreatitis diabetes mellitus (PPDM), but not pancreatic cancer-related diabetes (PCRD).
Jaelim Cho, MD, MPH, of the University of Auckland in New Zealand, and colleagues used nationwide pharmaceutical distribution data (2006 to 2015) linked to hospital discharge data to identify 1,862 individuals with PCRD or PPDM.
The researchers found that in individuals with PCRD, always metformin users (adjusted hazard ratio [aHR], 0.54) and insulin users (aHR, 0.46) had significantly lower mortality risks than patients who never used diabetes medications. However, these associations were weakened with the use of a 6-month interval.
In individuals with PPDM, compared to those who had never used antidiabetic drugs, all metformin users had a significantly lower risk of mortality (aHR, 0.51; 95% confidence interval [CI], from 0.36 to 0.70), while insulin users had never used antidiabetic drugs. a significantly changed mortality risk (aHR, 0.75; 95% CI, 0.49 to 1.14).
Even with a 6-month interval, the association between use of m. and mortality risk remained significant.
“Reverse causality may play a role in the association between insulin use and mortality in PCRD,” the authors write.
Metformin may reduce the risk of death from certain cancers for postmenopausal women with type 2 diabetes, according to a study published in the International Journal of Cancer.
The study team looked at data from 145,826 postmenopausal women between the ages of 50 and 79. The information was collected between 1993 and 1998 and came from the Women's Health Initiative study.
Looking at specific cancers, the researchers found that the risk for postmenopausal women with diabetes appeared to be about 25 to 35 percent higher for developing colon and endometrial cancers and non-Hodgkin's lymphoma. Women's risk was more than doubled for liver and pancreatic cancer. The researchers also found that for women with type 2 diabetes and cancer, the odds of dying from cancer were higher than for women with cancer who did not have diabetes (hazard ratio: 1.46).
In women with cancer who were taking m. to treat type 2 diabetes, the risk of dying from cancer was reduced overall compared to that observed in users of other drugs (hazard ratio 1.08 versus 1.45).
“M. users, particularly long-term users, may have a lower risk of developing certain cancers and dying from cancer than users of other antidiabetic drugs,” the authors write. “Future studies are needed to determine the long-term effect of m. on cancer risk and cancer survival”.
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