Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer.
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SUBMITTER: Garrett CR
PROVIDER: S-EPMC3326682 | biostudies-other | 2012 Apr
REPOSITORIES: biostudies-other
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Project description:BackgroundObservational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study.Methods2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n=84); women with diabetes with no metformin use (n=128); and women without diabetes (n=1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile.ResultsAfter adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40-1.38, p=0.67) and to women without diabetes (HR 1.00; 95% CI 0.61-1.66, p=0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38-1.55, p=0.47) and for overall survival was 0.86 (95% CI 0.49-1.52; p=0.60).ConclusionsIn postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.
| S-EPMC3769471 | biostudies-literature
Project description:BackgroundExisting literature suggests that metformin, the most commonly used biguanide, may lower colorectal cancer risk. Because most colorectal cancers originate in precancerous adenomas, we examined whether metformin use lowered colorectal adenoma risk after polypectomy in patients with type-2 diabetes.MethodsRetrospective cohort study of 40- to 89-year-old Kaiser Permanente Northern California patients who had type 2 diabetes, and ≥1 adenoma detected at baseline colonoscopy during 2000 to 2009 and a repeat colonoscopy 1 to 10 years from baseline adenoma diagnosis through 2012. Cox models evaluated the association between metformin use during follow-up and subsequent adenoma diagnoses, controlling for age, race/ethnicity, sex, body mass index, and repeat examination indication.ResultsStudy included 2,412 patients followed for a median of 4.5 years; cumulatively, 1,117 (46%) patients had ≥1 adenoma at repeat colonoscopy. Compared with patients not receiving diabetes medications (n = 1,578), metformin-only use (n = 457) was associated with lower adenoma recurrence risk [adjusted HR, 0.76; 95% confidence interval (CI), 0.65-0.89], and the association was stronger with increasing total metformin dose [quartile (Q) 1: HR, 0.90; 95% CI, 0.72-1.12; Q2: HR, 0.89; 95% CI, 0.70-1.12; Q3: HR, 0.80; 95% CI, 0.63-1.01; Q4: HR, 0.50; 95% CI, 0.42-0.60, Ptrend < 0.001]. Findings were unchanged in sensitivity analyses, including evaluating only outcomes during the 3- to 10-year period from baseline.ConclusionOur study suggests a potential benefit of metformin use in lowering the risk of subsequent adenomas after polypectomy in patients with type 2 diabetes.ImpactMetformin may lower colorectal cancer risk by reducing the formation of precancerous lesions, reinforcing the potential additional benefits of its use.
| S-EPMC4633388 | biostudies-literature
Project description:BackgroundMetformin has been associated with improved colorectal cancer survival, but investigations are limited by small numbers of patients and confounding by diabetic severity. We examined the association between metformin use and overall survival (OS) in patients with diabetes and colorectal cancer in a large population of U.S. veterans, while adjusting for measures of diabetic severity.MethodsPatients diagnosed with colorectal cancer from January 2001 to December 2008 were identified from the Veterans Affairs Central Cancer Registry. Multivariable models were used to examine the adjusted association of OS with diabetes and use of antidiabetic medications.ResultsThere were 21,352 patients diagnosed with colorectal cancer identified (n = 16,355 nondiabetic patients, n = 2,038 diabetic patients on metformin, n = 2,136 diabetic patients on medications other than metformin, n = 823 diabetic patients not on antidiabetic medication). Diabetic patients had a significantly worse OS than nondiabetic patients, but metformin users had only a 10% increase in death (HRadj 1.10; 95% CI, 1.03-1.17, P = 0.004), as compared with 22% for users of other antidiabetic medications (HRadj 1.22; 95% CI, 1.15-1.29, P < 0.0001). Among colorectal cancer patients with diabetes, metformin users had a 13% improved OS versus patients taking other antidiabetic medications (HRadj 0.87; 95% CI, 0.79-0.95, P = 0.003), while diabetic patients not on any antidiabetic medications did not differ with respect to OS (HRadj 1.02; 95% CI, 0.90-1.15, P = 0.76).ConclusionsAmong diabetics with colorectal cancer, metformin use is associated with improved survival, despite adjustments for diabetes severity and other risk factors.ImpactThese data lend further support to the conduct of randomized studies of possible anticancer effects of metformin among patients with colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(10); 1418-25. ©2016 AACR.
| S-EPMC5050110 | biostudies-literature
Project description:Background: Metformin use reportedly reduces cancer risk and improves survival in lung cancer patients. This study aimed to investigate the effect of metformin use in patients with diabetes mellitus (DM) and lung cancer receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Methods: A nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. From January 1, 2004, to December 31, 2012, a total of 373 metformin and 1260 non-metformin lung cancer cohorts with type 2 DM and EGFR-TKI treatment were studied. Results: Metformin use was significantly associated with a reduced risk of death (hazard ratio: 0.73, 95% confidence interval [CI]: 0.62-0.85, P < .001), as well as a significantly longer median progression-free survival (9.2 months, 95% CI: 8.6-11.7, vs 6.4 months, 95% CI: 5.9-7.2 months, P < .001) and median overall survival (33.4 months, 95% CI: 29.4-40.2, vs 25.4 months, 95% CI: 23.7-27.2 months, P < 0.001). Conclusions: In conclusion, metformin may potentially enhance the therapeutic effect and increase survival in type 2 DM patients with lung cancer receiving EGFR-TKI therapy.
| S-EPMC6696848 | biostudies-literature
Project description:BackgroundType 2 diabetes increases risk of developing colorectal cancer, but the association of preexisting diabetes with colorectal cancer survival remains unclear.MethodsWe analyzed survival by diabetes status at cancer diagnosis among 4,038 patients with colorectal cancer from two prospective U.S. cohorts. Cox proportional hazards regression was used to calculate HRs and 95% confidence intervals (CI) for overall and cause-specific mortality, with adjustment for tumor characteristics and lifestyle factors.ResultsIn the first 5 years after colorectal cancer diagnosis, diabetes was associated with a modest increase in overall mortality in women (HR, 1.22; 95% CI, 1.00-1.49), but not in men (HR, 0.83; 95% CI, 0.62-1.12; P heterogeneity by sex = 0.04). Beyond 5 years, diabetes was associated with substantially increased overall mortality with no evidence of sex heterogeneity; in women and men combined, the HRs were 1.45 (95% CI, 1.09-1.93) during >5-10 years and 2.58 (95% CI, 1.91-3.50) during >10 years. Compared with those without diabetes, patients with colorectal cancer and diabetes had increased mortality from other malignancies (HR, 1.78; 95% CI, 1.18-2.67) and cardiovascular disease (HR, 1.93; 95% CI, 1.29-2.91). Only women with diabetes for more than 10 years had increased mortality from colorectal cancer (HR, 1.33; 95% CI, 1.01-1.76).ConclusionsAmong patients with colorectal cancer, preexisting diabetes was associated with increased risk of long-term mortality, particularly from other malignancies and cardiovascular disease.ImpactOur findings highlight the importance of cardioprotection and cancer prevention to colorectal cancer survivors with diabetes.
| S-EPMC8026573 | biostudies-literature
Project description:AimsThe relationship between metformin therapy and the risk of coronavirus disease (COVID-19) has not been reported among patients with type 2 diabetes mellitus (DM). We aimed to investigate whether metformin therapy was associated with the incidence of COVID-19 among type 2 DM patients in South Korea.MethodsThe National Health Insurance Service-COVID-19 cohort database, comprising COVID-19 patients from 1 January 2020 to 4 June 2020, was used for this study. Among them, adult patients with type 2 DM were included in this study. Metformin users were defined as those who had been prescribed continuous oral metformin for over a period of???90 days, and the control group was defined as all other patients.ResultsOverall, 27,493 patients with type 2 DM (7204, metformin user group; 20,289, control group) were included. After propensity score matching, 11,892 patients (5946 patients in each group) were included in the final analysis. In the logistic regression analysis, the odds of metformin users developing COVID-19 was 30% lower than that of the control group [odds ratio (OR): 0.70, 95% confidence interval (CI): 0.61-0.80; P?<?0.001]. However, in the multivariate model, metformin use was not associated with hospital mortality when compared with that of the control group (OR: 1.26, 95% CI: 0.81-1.95; P?=?0.301).ConclusionsMetformin therapy might have potential benefits for the prevention of COVID-19 among patients with type 2 DM in South Korea. However, it did not affect the hospital mortality of type 2 DM patients diagnosed with COVID-19.
| S-EPMC7882044 | biostudies-literature
Project description:BackgroundSeveral studies suggest that metformin has the potential effect of reducing cancer risk. However, its survival benefit in patients with colorectal cancer (CRC) and diabetes is unknown. The aim of our study is to address the effect of metformin on outcomes for CRC based on a systematic review and meta-analysis.Methods and findingsWe searched EMBASE and MEDLINE databases from inception through August, 2013, using search terms related to metformin, diabetes, colorectal cancer, and prognostic outcome. The outcome measures were hazard ratios (HRs) with 95% CIs comparing CRC survival in diabetic patients using metformin and without using metformin. The primary end points were overall survival (OS) and CRC specific survival (CS). A total of six cohort studies including 2,461 patients met full eligibility criteria. The pooled HR favoring metformin users was 0.56 for OS (95% CI, 0.41 to 0.77) and 0.66 for CRC-specific survival (95% CI, 0.50 to 0.87). Thus metformin therapy reduced the risk of all cause of death by 44% and the risk of CRC specific death by 34% in CRC patients compared to those in non-users. However, evidence of heterogeneity and possible publication bias was noted for OS.ConclusionsPatients with CRC and diabetes treated with metformin appear to have an improved survival outcome. Prospective study should be warranted to examine the association between metformin exposure intensity as well as some other confounding variables and survival outcome in diabetic CRC patients.
| S-EPMC3960145 | biostudies-literature
Project description:ContextPrediabetes is prevalent and significantly increases lifetime risk of progression to type 2 diabetes. This review summarizes the evidence surrounding metformin use for type 2 diabetes prevention.Evidence acquisitionArticles published between 1998 and 2017 examining metformin use for the primary indication of diabetes prevention available on MEDLINE.Evidence synthesisForty articles met inclusion criteria and were summarized into four general categories: (1) RCTs of metformin use for diabetes prevention (n=7 and n=2 follow-up analyses); (2) observational analyses examining metformin use in heterogeneous subgroups of patients with prediabetes (n=9 from the Diabetes Prevention Program, n=1 from the biguanides and the prevention of the risk of obesity [BIGPRO] trial); (3) observational analyses examining cost effectiveness of metformin use for diabetes prevention (n=11 from the Diabetes Prevention Program, n=1 from the Indian Diabetes Prevention Program); and (4) real-world assessments of metformin eligibility or use for diabetes prevention (n=9). Metformin was associated with reduced relative risk of incident diabetes, with the strongest evidence for use in those at highest risk (i.e., aged <60 years, BMI ≥35, and women with histories of gestational diabetes). Metformin was also deemed cost effective in 11 economic analyses. Recent studies highlighted low rates of metformin use for diabetes prevention in real-world settings.ConclusionsTwo decades of evidence support metformin use for diabetes prevention among higher-risk patients. However, metformin is not widely used in real-world practice, and enhancing the translation of this evidence to real-world practice has important implications for patients, providers, and payers.
| S-EPMC6613947 | biostudies-literature
Project description:Accumulating evidence suggests that metformin reduces the incidence and mortality of colorectal cancer (CRC). However, underlying mechanisms have not been fully clarified. The aim of this study was to examine the pathological characteristics of resected CRC from patients treated with metformin for type 2 diabetes mellitus (DM). In total, 267 patients with DM underwent curative colectomy for Stage I-III CRC and 53 (19.9%) patients had been treated medically including metformin. Pathological N-stage was significantly lower in metformin-treated patients (P < .05) with prolonged disease-free survival (DFS) (P < .05). Immunohistochemistry showed that the densities of CD3(+) and CD8(+) tumor-infiltrating lymphocytes (TILs) in the invasive front area were significantly higher in 40 patients treated with metformin compared with propensity score matched cases without metformin (P < .05). The density of tertiary lymphoid structures (TLS) in tumor stroma was markedly increased in metformin-treated patients (P < .001). In those tumors, there were more CD68(+) tumor-associated macrophages (TAM) infiltrated (P < .05), while the ratio of CD163(+) M2-phenotype was markedly reduced (P < .001). Stromal fibrosis tended to be suppressed by metformin intake (P = .051). These findings suggested that metformin drastically changes the characteristics of infiltrating immune cells in CRC and reprograms the tumor microenvironment from immunosuppressive to immunocompetent status, which may lead to suppression of microscopic tumor spread and improve the outcomes of patients with CRC and type 2 DM.
| S-EPMC7648042 | biostudies-literature
Project description:AimsTo compare the risks of all-cause mortality, hepatic outcomes, major adverse cardiovascular events between metformin users and nonusers for patients with diabetes and cirrhosis.MethodsFrom the Taiwan's National Health Insurance Research Database, we selected propensity-score matched metformin users and nonusers from the cohorts of type 2 diabetes mellitus with compensated (n = 26 164) or decompensated liver cirrhosis (n = 15 056) between 1 January 2000 and 31 December 2009, and followed them until 31 December 2010. Cox proportional hazards models with robust sandwich standard error estimates were used to assess risk of investigated outcomes for metformin users.ResultsThe incidence rates of mortality during follow-up were 3.8 and 3.3 per 100 patient-years (adjusted hazard ratio [aHR] 1.13, 95% confidence interval 1.01-1.25) for metformin users and nonusers, respectively. The incidence rates of cirrhotic decompensation during follow-up were 5.9 and 4.9 per 100 patient-years (aHR 1.15, 95% confidence interval 1.04-1.27) for metformin users and nonusers. The risk of death (P for trend <.01) and cirrhotic decompensation (P for trend <.0001) associated with metformin use was significant for those taking metformin for >40 defined daily doses in 90 days or >1000 mg/d. The outcomes of metformin use vs nonuse for type 2 diabetes mellitus with decompensated liver cirrhosis were not statistically different, except that metformin users had higher risk of mortality (aHR 1.15).ConclusionMetformin use was associated with higher risks of mortality and cirrhotic decompensation in patients with compensated liver cirrhosis. Prospective studies are required to confirm our results.
| S-EPMC9292486 | biostudies-literature