Effects Of Metformin In Patients Research Articles

Renal protective effect of metformin in type 2 diabetes patients.

Inhibiting the development and progression of diabetic kidney disease (DKD) is an important issue, but the renoprotective effect of metformin is still controversial. To assess the renoprotective effect of metformin in patients with type 2 diabetes. This retrospective observational multicenter cohort study included 316,693 patients with type 2 diabetes from seven hospital. After age, gender, medical year, baseline estimated glomerular filtration rate (eGFR), urine protein (dipstick), glycated hemoglobin (HbA1C) and propensity score matching; a total of 13,096 metformin and 13,096 non-metformin patients were included. The main results were doubling of serum creatinine, eGFR ≤ 15 mL/min/1.73 m2 and end stage kidney disease (ESKD). After conducting a multivariable logistic regression analysis on the variables, the metformin group was revealed to have better renal outcomes than non-metformin group, including a lower incidence of doubling of serum creatinine (hazard ratio [HR], 0.71; 95% CI, 0.65-0.77), eGFR ≤ 15 mL/min/1.73 m2 (HR 0.61; 95% CI 0.53-0.71), and ESKD (HR 0.55; 95% CI 0.47-0.66). The subgroup analyses revealed a consistent renoprotective effect across patients with various renal functions. Furthermore, when considering factors such as age, sex, comorbidities, and medications in subgroup analyses, it consistently showed that the metformin group experienced a slower deterioration in renal function across nearly all patient subgroups. Metformin decreased the risk of renal function deterioration.

Clinical outcomes with metformin use in diabetic patients with compensated cirrhosis: a systematic review and meta-analysis.

Previous studies have demonstrated a beneficial effect of metformin in patients with cirrhosis, but no improvement in liver histology. To investigate the impact of metformin on mortality and hepatic decompensation in people with diabetes with compensated cirrhosis. Medline, Embase and Cochrane databases were searched from inception to February 2023 for studies reporting results regarding the impact of metformin on all-cause mortality and hepatic decompensation in people with diabetes with compensated cirrhosis. The risk of bias was assessed by ROBINS-I Cochrane tool. R software 4.3.1 was used for all analyses. Six observational studies were included in the final analysis. Metformin use was associated with reduced all-cause mortality or liver transplantation [hazard ratio (HR): 0.55; 95% confidence interval (CI) 0.37-0.82], while no benefit was shown in the prevention of hepatic decompensation (HR: 0.97; 95% CI: 0.77-1.22). In the subgroup analysis, metformin use was associated with reduced all-cause mortality or liver transplantation (HR: 0.50; 95% CI 0.38-0.65) in patients with metabolic-associated steatohepatitis cirrhosis, while two studies reported no survival benefit in patients with cirrhosis due to hepatitis C (HR: 0.39; 95% CI 0.12-1.20). Metformin use is associated with reduced all-cause mortality, but not with the prevention of hepatic decompensation in people with diabetes with compensated cirrhosis. The mortality benefit is most likely driven by better diabetes and cardiovascular health control.

Metabolic effects of metformin in patients with type 2 diabetes mellitus and new coronavirus infection

Metabolic effects of metformin in patients with type 2 diabetes mellitus and new coronavirus infection

Metformin may improve the outcome of patients with colorectal cancer and type 2 diabetes mellitus partly through effects on neutrophil extracellular traps

BackgroundAlthough metformin reduces the risk of cancer-related mortality in patents with type 2 diabetes, the mechanism of its anti-cancer effects has not been fully understood.MethodImpact of metformin on survival was examined in patients who underwent curative colectomy for colorectal cancer (CRC). The effects of metformin in neutrophil extracellular traps (NETs) were examined with in-vitro experiments and multiplex immunohistochemistry of surgically resected CRC specimens.ResultsPrior intake of metformin prolonged relapse-free (P = 0.036) and overall survival (P = 0.041) in 289 patients with T2DM to the comparable levels to those of 1576 non-diabetic patients. Metformin reduced the production of NETs stimulated with lipopolysaccharide or HT-29 colon cancer cells to 60% of control. Neutrophils markedly suppressed the chemotactic migration of activated T cells in an NET-dependent manner, which was reversed by metformin treatment up to approximately half of the migration without neutrophils. Immunohistochemical analysis revealed a significant association between metformin intake and a reduction in the numbers of tumor-associated neutrophils (TANs) and NETs. Simultaneously, metformin intake was found to increase the presence of CD3(+) and CD8(+) tumor-infiltrating T cells (TILs), particularly at the tumor-invasion front, especially in areas with fewer TANs and NETs.ConclusionMetformin suppresses the diabetes-associated enhancement of NET formation, which can augment the infiltration of TILs in CRC tissues. The anti-tumor effect of metformin in patients with T2DM may be, at least partly, attributable to the inhibition of NETs.

Genetic Polymorphism in the Organic Cation Transporters 1 (OCT1) Gene and its Effect on Therapeutic Efficacy and Gastrointestinal Side Effects of Metformin in Patients with Type 2 Diabetes Mellitus in Basrah/ Southern Iraq.

Objectives: This study aims to detect the association of the OCT1 genetic polymorphism with the efficacy and gastrointestinal side effects of metformin in newly diagnosed type 2 diabetes and drug naïve patients in Basrah/Southern Iraq. Methods: This was a prospective cohort population-based study of (102) newly diagnosed type 2 diabetics from February 2022 to December 2022. Newly diagnosed type 2 diabetes, drug naïve patients with an HbA1c range of (6.5-9.9) were included in the study. All the participants received immediate-release metformin. Metformin responders were patients whose HbA1c levels decreased by ≥1% after three months of treatment. Patients were genotyped for one of the most common SNPs in the OCT1 gene (SLC22A1): M420del (rs72552763) of axon 7, using ARMS- PCR genotyping assays. Results: Gastrointestinal side effects were observed in 15% of the patients. Out of the total of 102 participants, 69 were responders and 33 were non-responders. The homozygous genotype (AA) “reference type” of the SLC22A1 (rs72552763) gene polymorphism was significantly found in the responders' group; p-value = 0.0001. The homozygous genotypes (deletion/deletion) of the SLC22A1 (rs72552763) gene were more common among the non-responders' group; p-value = 0.0001. About 87% of those with gastrointestinal side effects carried the AA genotype. All the patients without gastrointestinal side effects carried the homozygous del/del genotype; P-value 0.005. Conclusions There was a significant association between the rs72552763 gene polymorphism and metformin efficacy and GI side effects.

Abstract 12196: Effect of Metformin on Heart Failure in Patients With Diabetes Mellitus Receiving Anthracycline Chemotherapy

Introduction: The prevention of heart failure (HF) is an essential issue in patients treated with anthracyclines, however, existing treatments have demonstrated modest effects. Metformin (MET), widely used to treat diabetes, protects from anthracyclines-induced cardiotoxicity in vitro and in murine models. However, there is no research investigating the cardioprotective effects of MET in patients treated with anthracyclines. Hypothesis: MET is cardioprotective in patients treated with anthracyclines. Methods: Out of 5655 patients undergoing new anthracyclines therapy at a tertiary center between 2008-2021, 260 patients were treated with MET. The clinical characteristics associated with the use of MET were identified and a propensity-score (gender, diabetes, type of cancer, kidney and cerebrovascular disease) used to match 200 patients treated with MET to 200 patients without MET. The primary outcome was new-onset symptomatic HF defined by the AHA/ACC guidelines occurring within 1 year of the initiation of anthracyclines. Proportional hazard analysis was used to identify characteristics associated with HF. Results: Patients were 65 years old [57-70], 34% male. No differences were noted in age, cardiovascular risk factors, history, use of beta-blockers and ACE inhibitors between the MET and non MET groups. Six patients (3%) treated with MET and 20 matched patients (10%) developed HF within 1 year of anthracyclines initiation (P=0.004, Figure). Use of MET ([HR]: 0.27; 95% CI: 0.1 to 0.64; p = 0.002), use of insulin (HR: 2.27; 95% CI: 1.05 to 5; p = 0.04), coronary artery disease (HR: 4.69; 95% CI: 2.06 to 10.2; p < 0.001), and chronic kidney disease (HR: 2.65; 95% CI: 1.21 to 5.77 p = 0.02) were associated with incident HF. Conclusions: MET significantly reduced the risk for HF in patients treated with anthracyclines. Our findings are consistent with previous experimental studies and suggest a new therapeutic option in the prevention of cardiotoxicity.

Role of Metformin in the Management of Polycystic Ovarian Syndrome-Associated Acne: A Systematic Review.

Metformin, a biguanide hypoglycemic agent that is safe and effective for treating acne in women with the polycystic ovarian syndrome (PCOS), has shown growing evidence of improving insulin resistance, hyperandrogenism, dyslipidemia, overall cardiovascular health, quality of life, psychological wellbeing, and general health outcomes. This study aims to identify and summarize the effects of metformin in patients with PCOS-associated acne. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was done on PubMed, PubMed Central, Cochrane, Google Scholar, and Science Direct databases from 2011 up to 23 February 2022. Randomized controlled trials (RCTs), cross-sectional studies, observational studies, literature reviews, systematic reviews, and meta-analyses published in English were selected. The data was extracted to a predefined template. Each study was individually checked by using a quality assessment. The initial search generated a total of 218 studies. Nine studies were included in the final selection: two RCTs, one hospital-based longitudinal study, one hospital-based clinical trial, three cross-sectional studies, three systematic reviews with meta-analyses, and one narrative review. Metformin is generally effective and safe for improving PCOS-associated acne and the quality of life. More clinical trials are required to determine the indications for prescribing metformin in patients with PCOS-associated acne.

The effect of metformin on the survival of colorectal cancer patients with type 2 diabetes mellitus

Evidence from previous studies suggests a protective effect of metformin in patients with colorectal cancer (CRC). The aim of this study was to examine the associations between metformin use and overall survival (OS) and disease-free survival (DFS) in CRC patients with type 2 diabetes mellitus (DM). We retrospectively included patients who underwent surgery for CRC at Limoges’ University Hospital between 2005 and 2019 and diagnosed with type 2 DM. Data on the characteristics of patients, CRC, comorbidities and drug exposure were collected from the electronic medical records. The exposure was the use of metformin and the outcomes were OS and DFS. We identified 290 CRC patients with type 2 DM. A total of 144 (49.7%) of them were treated with metformin. Metformin users were significantly younger, with higher body mass index and less diabetes-related complications compared to non-users. The 2-year OS was significantly higher in metformin users than in non-users (86.9 ± 2.9% vs. 71.0 ± 4.0%, p = 0.001). In multivariate analysis, metformin use was associated with better OS (adjusted hazard ratios [aHR] = 0.45 95% confidence interval [95% CI]: 0.21–0.96) and better DFS (aHR = 0.31; 95% CI: 0.18–0.54). In conclusion, the use of metformin may improve OS and DFS in CRC patients with type 2 DM.

Effect of metformin use on clinical outcomes and serum urate in gout patients with diabetes mellitus: a retrospective cohort study

ObjectiveGout and diabetes mellitus type 2 (DM) frequently co-exist. The pharmacological effects of metformin may include anti-inflammatory and urate lowering effects. The objective of this study was to test these effects in patients with gout starting uric acid lowering treatment (ULT) in secondary care.MethodsRetrospective cohort study including patients with gout and DM starting ULT. Differences in the incidence density of gout flares, proportion of patients reaching target sUA in the first six months after starting ULT, and difference in mean allopurinol dose at sUA target were compared between users of metformin and users of other or no anti-diabetic drugs (control group). Correction for confounding was applied.ResultsA total of 307 patients were included, of whom 160 (52.1%) used metformin. The incidence of flares was 1.61 and 1.70 in the first six months for respectively the metformin group and control group. The incidence rate ratio for gout flares was not significant (0.95, 95% CI 0.78 to 1.14). At six months, 62.8% and 54.9% reached target sUA in the metformin and control group respectively, corrected odds ratio of 1.09 (95% CI 0.66 to 1.80). There was no difference in mean allopurinol dose at sUA target 266 mg for metformin users and 236 mg for the control group, difference 30 mg (95% CI − 4.7 to 65.5).ConclusionsIn conclusion we could not confirm a clinically relevant anti-inflammatory or urate lowering effect of metformin in patients starting ULT treatment and receiving usual care flare prophylaxis.

Adverse Biochemical and Physiological Effects of Metformin in Diabetic Type-2 Patients, A Comparative Clinical Study

Task: The aims and objectives of present study were to highlight the efficacy and adverse side effects of metformin in patients with diabetes type-2 and this study was conducted from December 2021to May 2022 in different medical and diabetic centers of Pakistan. Materials and methods: Subjects: 700 male and female subjects were selected for this study. Division of individuals: 100 normal individuals were in Control group, further 600 individuals were divided into three different groups. In group-X, 200 diabetic type-2, patients were taking 2000 mg/day metformin and in group-Y, 200 diabetic type-2, patients were taking 1500 mg/day metformin while in group-Z, 200 diabetic type-2, patients were taking 500 mg/day metformin respectively. Parameters: Fasting and random serum glucose levels, blood lactic acid levels, serum creatinine levels, myoglobin blood levels and blood hemoglobin levels. Analysis: Microlab and Spectrophotometry kit, regent method were used for the measurement of different parameters. Bio-statistical presentation: All collected raw data were interoperated bio-statistically through the application of SPSS version 2000, in which all parameters were described with the application of standard mean deviation and significant (p<0.05) regression.

Predicting the effectiveness of metformin in patients with type 2 diabetes mellitus from molecular genetic positions

Predicting the effectiveness of metformin in patients with type 2 diabetes mellitus from molecular genetic positions

Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study.

ContextGlucocorticoid excess exhibits multiple detrimental effects by its catabolic properties. Metformin was recently suggested to protect from adverse metabolic side-effects of glucocorticoid treatment. Whether metformin is beneficial in patients with endogenous glucocorticoid excess has not been clarified.ObjectiveTo evaluate the phenotype in patients with endogenous Cushing’s syndrome (CS) treated with metformin at the time of diagnosis.Patients and MethodsAs part of the German Cushing’s Registry we selected from our prospective cohort of 96 patients all 10 patients who had been on pre-existing metformin treatment at time of diagnosis (CS-MET). These 10 patients were matched for age, sex and BMI with 16 patients without metformin treatment (CS-NOMET). All patients had florid CS at time of diagnosis. We analyzed body composition, metabolic parameters, bone mineral density and bone remodeling markers, muscle function and quality of life.ResultsAs expected, diabetes was more prevalent in the CS-MET group, and HbA1c was higher. In terms of comorbidities and the degree of hypercortisolism, the two groups were comparable. We did not observe differences in terms of muscle function or body composition. In contrast, bone mineral density in metformin-treated patients was superior to the CS-NOMET group at time of diagnosis (median T-Score -0.8 versus -1.4, p = 0.030). CS-MET patients showed decreased β-CTX levels at baseline (p = 0.041), suggesting reduced bone resorption under metformin treatment during glucocorticoid excess.ConclusionThis retrospective cohort study supports potential protective effects of metformin in patients with endogenous glucocorticoid excess, in particular on bone metabolism.

Metformin Exerts Anti-inflammatory and Mucus Barrier Protective Effects by Enriching Akkermansia muciniphila in Mice With Ulcerative Colitis.

The present study aimed to determine if metformin exerts anti-inflammatory and mucus-protective effects via the gut microbiota. Metformin has extensive benefits including anti-inflammatory effects. Previous studies showed that metformin changed the gut microbiota composition and increases the number of goblet cells. Intestinal dysbiosis and goblet cell depletion are important features of ulcerative colitis (UC). The underlying mechanism and whether metformin can improve the mucus barrier in UC remain unclear. Metformin (400 mg/kg/day) was administered to mice with dextran sulfate sodium (DSS)-induced UC for 2 wk to investigate the effects of metformin on the intestinal mucus barrier. The gut microbiota was depleted, using antibiotics, to explore its role in the mucus-protecting effects of metformin. Akkermansia muciniphila (A. muciniphila), which was enriched in metformin-treated mice, was administered to mice to investigate the effects of the bacteria on UC and the mucus barrier. Metformin attenuated DSS-induced UC in mice, as evidenced by the alleviation of diarrhea, hematochezia, and the decrease in body weight. The expression of mucin2, a prominent mucus barrier protein, was increased in the metformin-treated group compared to the DSS-treated group. Furthermore, fecal 16S rRNA analysis showed that metformin treatment changed the gut microbiota composition by increasing the relative abundance of Lactobacillus and Akkermansia species while decreasing Erysipelatoclostridium at the genus level. Antibiotic treatment partly abolished the anti-inflammatory and mucus-protecting effects of metformin. Administration of A. muciniphila alleviated the colonic inflammation and mucus barrier disruption. Metformin alleviated DSS-induced UC in mice and protected against cell damage via affecting the gut microbiota, thereby providing a new mechanism for the therapeutic effect of metformin in patients with UC. This study also provides evidence that A. muciniphila as a probiotic has potential benefits for UC.

Імунні та протизапальні фактори в механізмі лікувальної дії метформіну при цукровому діабеті 2-го типу (аналітичний огляд із включенням власних даних)

Огляд присвячений аналізу сучасної літератури, включаючи результати власних досліджень, що стосуються механізму лікувальної дії метформіну у хворих на цукровий діабет 2-го типу (ЦД2) і його ускладнень. Незважаючи на те, що метформіном лікується величезна кількість хворих у всьому світі і є велика кількість публікацій, в яких обговорюється його клінічний ефект, механізм лікувальної дії метформіну при ЦД2 залишається ще не зовсім ясним. В роботі подані нові дані, які вказують на те, що в механізмі лікувального ефекту метформіну при ЦД2 і його ускладненнях істотну роль відіграє не тільки гіпоглікемічний ефект метформіну, але й його сприятливий вплив на порушені при ЦД2 імунорегуляторні процеси і запалення, про що свідчать зменшення індексу запалення, нормалізація кількості і функції лімфоцитів різного імунофенотипу і зниження рівня прозапальних цитокінів і хемокінів у крові.

Effect of Metformin in Patients with ALL Who Express High Levels of the ABCB1 Gene and Its Impact on Survival

OBJECTIVES. In acute lymphoblastic leukemia (ALL), high levels ABCB1 gene expression have been associated with treatment resistance. Metformin has been reported to decrease the level of ABCB1 gene expression. The objective of this study was to evaluate the effect of metformin on the treatment regimen in patients with ALL who exhibit high levels of ABCB1 gene expression and its impact on overall survival.METHODS. A total of 102 patients with ALL were recruited; one group (n = 26) received metformin, and the other received chemotherapy (n = 76). Measurement of ABCB1 transcript expression was performed using qRT-PCR prior to treatment initiation. Survival analysis was performed using Kaplan-Meier curves. The impact of both the type of treatment and the level of expression on the response (remission or relapse) was analyzed by calculating the odds ratio.RESULTS. A total of 102 patients with B-immunophenotype-free ALL were enrolled and divided into two groups: metformin users (n = 25) and metformin non-users (n = 76). The mean for the Metformin User group was 31 (range of 18-61), with 93 x 103/mcl leukocytes (range of 1.2-870 x 103/mcl). Regarding the Metformin Non-User group, the mean age was 35 years (range 18-78), most of the patients were women 52.6% (n = 40), and the patients had a lower mean leukocyte level of 45.1 x 103/mcl (range 0.4-251 x 103/mcl).When analyzing the relative ABCB1 gene expression levels prior to initiation of treatment in the 102 patients, 45.1% (46/102) had high expression levels, 19.6% (20/102) had low levels, and only 35.2% (36/102) did not express the gene. The proportions of patients with high expression were similar in the two treatment groups (in the metformin User group and in the metformin Non-User group)The effect of expression levels of the ABCB1 gene on Global Survival (OS) at 60 months demonstrated that high levels of ABCB1 gene expression were associated with a lower OS of 41.5% (19/46) in ALL patients; low and negative expression had OS values of 70% (14/20) and 69.5% (25/36), respectively. The results indicated a significant decrease in survival in patients with high levels of ABCB1 gene expression, similar to our previously reported findings (p ≤ 0.030, log-rank test)However, when evaluating the two treatment groups (metformin users and metformin non-users), there were no significant differences between the groups (p = 0.251, 95% confidence interval [CI]), confirming that no therapeutic benefit was evident in the OS in 102 patients, without considering ABCB1 gene expression levels. Therefore, we analyzed only those patients who reported high levels of ABCB1 gene expression (46/102) and its effect on OS. In these patients, increased survival was observed in the metformin user group (83.3%, 10/12) compared with the metformin non-user group (26.6%, 9/34), decreasing the risk of therapeutic failure (p = 0.025, 95% CI). No significant changes were observed in OS in patients with low or negative levels of ABCB1 gene expression.These findings suggest that the use of metformin and steroids in the pre-induction stage depletes the energy reserves of ATP that could be required by the pg170-kDa transporter and increases the chemosensitivities of different chemotherapeutic drugs, increasing their efficacy only in patients with high levels of ABCB1 gene expression.When assessing the type of risk in the two treatment groups, in terms of refractoriness, only patients with high levels of ABCB1 gene expression demonstrated an increased risk of therapeutic failure (odds ratio [OR] 7.48; 95% CI, 0.3638-153.79) compared with other clinical variables, such as age over 35 years (OR 2.25, 95% CI, 0.3044-16.632) and white blood cell count (OR 6.00, 95% CI, 0.5626-63.987). Regarding relapse, high levels of ABCB1 gene expression were also associated with an increased risk of relapse (OR 2.91, 95% CI, 0.2808-30.299) compared with clinical variables such as age greater than 35 years (OR 3.42, 95% CI, 0.4944-23.775) and leukocyte count (OR 8.57, 95% CI, 0.8251- 89.043). In the metformin user group, metformin functioned as a protective factor against both therapeutic failure and early relapse (OR 0.07, 95% CI, 0.0037-1.538) and (OR 0.05; 95% CI, 0.0028-1.153)Survival of those patients with high ABCB1 expression was lower than those with low or absent gene expression (p = 0.030).CONCLUSIONS. The combined use of metformin with chemotherapy is effective in patients with elevated levels of ABCB1 gene expression [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Safety and effectiveness of metformin in patients with reduced renal function: A systematic review.

To examine clinical and safety outcomes associated with metformin use in patients with impaired renal function. We searched PubMed and Embase databases from inception to August 2020, supplementing our search with a review of investigator files and reference lists of included studies. Any study reporting original data on metformin and patient-centred outcomes in patients with impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 , was included. Post hoc meta-analysis was performed for the outcomes of mortality, cardiovascular events and acidosis. Nine small prospective studies enrolling patients with significantly impaired renal function identified only one case of clinically apparent lactic acidosis. Among 13 larger retrospective studies, seven examined the risk of mortality across patient subgroups; meta-analysis showed reductions in overall mortality at an eGFR of 45 mL/min/1.73m2 or higher but not at an eGFR of less than 45 mL/min/1.73m2 . Eight retrospective studies evaluated acidosis as an outcome; meta-analysis showed no increase in risk of acidosis except at an eGFR of less than 30 mL/min/1.73m2 , in which group the HR was 1.97 (95% CI 1.03-3.77). The literature shows metformin to be associated with reduced mortality and no increased risk of acidosis at an eGFR of 45 mL/min/1.73m2 or higher. Metformin appears to be associated with fewer benefits and possible increases in the risk of acidosis at an eGFR of less than 30 mL/min/1.73m2 . Consistent with US Food and Drug Administration guidelines, metformin should not be used at an eGFR less than 30 mL/min/1.73m2 , and further research on its risk-benefit profile at eGFR values approaching 30 mL/min/1.73m2 is warranted.

Association Between Metformin and Prevention of Dementia in T2DM Adult Patients

Introduction: In 2020 the World Health Organization estimated that the number of people with dementia was 50 million in the world. Furthermore, it is expected about 10 million new cases every year. Alzheimer’s disease (AD) is the most common form of dementia, which represents more than 50% of the cases. Type 2 diabetes mellitus (T2DM) is a major risk factor for AD and dementia. Even in people without clinical dementia, diabetes is associated with decreased cognitive performance and with increased brain atrophy. If comparing general population and people with diabetes, patients with T2DM had a 73% higher risk of developing dementia and a 56% increased risk of developing AD. Typically, the first medication prescribed for T2DM is metformin and it has been associated with the reduction of cognitive decline and the risk of dementia in patients with T2DM when compared with diabetic patients without medication. A randomized, double-blinded, placebo-controlled study demonstrated that during metformin treatment there was an improvement of executive functioning, learning, memory, and attentional abilities. A possible explanations for the protective effect of metformin in patients with T2DM is that it prevents hyperinsulinemia and the formation of amyloid-β plaques in the brain and the onset of AD. Metformin does not only decrease the plasma glucose level in several mechanisms, but it also characterized to beneficially effect serum lipid profiles, reduce inflammatory cell adhesion to endothelium, and exert anti-inflammatory, anti-apoptotic and anti-oxidative properties. Method: A Clinical Scientific Research was made about correlation among dementia and metformin. Were searched and found in PubMed a total of 61 articles between 2015–2020, but only free access and those who correlated metformin and dementia were used. Results: Studies showed that T2DM patients taking metformin had decreased risk of developing dementia or AD if compared to others diabetic patients that were not taking metformin. However, it is being hard to test antidiabetic therapies in AD, because the mechanisms which tie T2DM to Alzheimer clinical syndrome are not totally known. Therefore, to be as effective as possible it is necessary to treat the patients before they develop extensive amyloid and tau tangle burden. Conclusion: Diabetic patients taking metformin have a protector factor to don’t develop dementia or AD, when compared to those who don’t take metformin since they started the treatment before accumulation of amyloid and tau protein in the brain.

Effect of metformin therapy on muscle mass and strength in patients with and without diabetes. Meta-analysis of 15 studies

Aim. To assess the parameters reflecting sarcopenia (body composition, muscle strength, muscle function) in order to determine the effectiveness of metformin in patients with sarcopenia.Material and methods. Systematic searches of clinical trials were carried out in MEDLINE databases through PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ResearchGate from January 1990 to March 2019. For statistical processing, the R language with the RStudio software was used. The following packages were used: googlesheets4, tidyverse, meta, dmetar, metafor. The metaanalysis included 391 patients with both established for the first time and existing long-term type 2 diabetes (T2D), with prediabetes, impaired glucose tolerance (IGT), as well as patients without impaired glucose metabolism. In comparison groups (194 patients who received metformin and 197 patients who received placebo), the effect of metformin on lean body mass (LBM), fat mass, muscle strength and muscle function was assessed, which made it possible to indirectly evaluate the potential effect of metformin on sarcopenia.Results. The use of metformin in patients with different glucose metabolism (type 2 diabetes, IGT, prediabetes) did not lead to significant changes in body composition (on average, LBM increased by 0,9 kg (MD, 0,8815; CI (-0,11; 1,87), p=0,0818), fat mass decreased by 0,7% (MD, -0,6856; CI (-1,54; 0,17), p=0,1170), but muscle strength significantly increased by 0,5 kg (SMD, 0,5241, CI (0,2265; 0,8217), p=0,0006).Conclusion. Meta-analysis has confirmed that the use of metformin has an effect on muscle strength, which makes it possible to consider it for sarcopenia treatment. Unfortunately, a small number of studies have not allowed to analyze the effect of metformin on a number of characteristics: muscle strength, muscle function (walking speed, functional tests). At the moment, a much larger prospective study is needed to form a final opinion on the rationale of metformin therapy in patients with sarcopenia.

The Current and Potential Therapeutic Use of Metformin-The Good Old Drug.

Metformin, one of the oldest oral antidiabetic agents and still recommended by almost all current guidelines as the first-line treatment for type 2 diabetes mellitus (T2DM), has become the medication with steadily increasing potential therapeutic indications. A broad spectrum of experimental and clinical studies showed that metformin has a pleiotropic activity and favorable effect in different pathological conditions, including prediabetes, type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM). Moreover, there are numerous studies, meta-analyses and population studies indicating that metformin is safe and well tolerated and may be associated with cardioprotective and nephroprotective effect. Recently, it has also been reported in some studies, but not all, that metformin, besides improvement of glucose homeostasis, may possibly reduce the risk of cancer development, inhibit the incidence of neurodegenerative disease and prolong the lifespan. This paper presents some arguments supporting the initiation of metformin in patients with newly diagnosed T2DM, especially those without cardiovascular risk factors or without established cardiovascular disease or advanced kidney insufficiency at the time of new guidelines favoring new drugs with pleotropic effects complimentary to glucose control. Moreover, it focuses on the potential beneficial effects of metformin in patients with T2DM and coexisting chronic diseases.

Inhibition of angiotensin-induced aortic aneurysm by metformin in apolipoprotein E–deficient mice

ObjectiveMetformin is associated with a reduced incidence and growth of abdominal aortic aneurysms (AAAs). The aim of the present study was to investigate the inhibitory effects of metformin on AAA development and possible underlying mechanisms in experimentally induced AAAs in mice, along with the possible synergistic effects of metformin and imatinib. MethodsAngiotensin II was used to induce AAAs in apolipoprotein E knockout (ApoE−/−) mice for 28 days. The mice were treated with metformin (n = 11), metformin combined with imatinib (n = 7), or vehicle (n = 12), starting 3 days before angiotensin II infusion. Ultrasound examination was used to analyze aneurysm formation. Cholesterol and blood pressure levels were measured at the start and end of the study. Gene array and quantitative polymerase chain reaction were used to analyze the changes in gene expression in the aorta. Wire myography was used to study vascular function. ResultsMetformin (n = 11) suppressed the formation and progression of AAAs by 50% compared with the vehicle controls (n = 12), with no further effects from imatinib (n = 7). Metformin reduced total cholesterol and mRNA expression of SPP1 (encoding osteopontin), MMP12, and the glycoprotein genes Gpnmb and Clec7a. Furthermore, metformin inhibited blood pressure increases and reduced vascular contractions, as determined by wire myography, and restored the anticontractile function of perivascular adipose tissue. ConclusionMetformin inhibited aneurysm formation and progression and normalized vascular function in ApoE−/− mice with no additional effect of imatinib. This might be mediated by the protective effects on vascular endothelial function and perivascular adipose tissue via reduced expression of genes promoting inflammation, including SPP1, MMP12, Gpnmb, and Clec7a. Clinical relevanceRetrospective studies of the effects of metformin in patients with aneurysm have so far only been performed of those with type 2 diabetes. The present study shows that metformin has effects on nondiabetic mice and revealed the mechanistic effects mediated by the drug that could also be important to study as outcomes in humans. Future clinical trials using metformin are warranted in patients without diabetes with abdominal aortic aneurysms.