Metformin Improves Overall Survival of Colorectal Cancer Patients with Diabetes: A Meta-Analysis.

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diabetes mellitus 5 endocrinologydiseases
hyperglycemia 2 endocrinologydiseases
hyperinsulinemia 2 endocrinologydiseases
metformin 45 endocrinologydiseasesdrugs
obesity 1 endocrinologydiseases

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metformin 459 has a higher risk of colorectal cancer (CRC) incidence and mortality than nondiabetics. The role of metformin in CRC prognosis is still controversial. The meta-analysis aims to investigate whether metformin improves
metformin 556 of metformin in CRC prognosis is still controversial. The meta-analysis aims to investigate whether metformin improves the survival of diabetic CRC patients. Methods. PubMed, EMBASE, and Cochrane Library were searched
metformin 1161 heterogeneity (I2 = 56.1% and p = 0.033) in our meta-analysis. An improved overall survival (OS) for metformin users over nonusers among colorectal cancers with diabetes was noted (HR 0.75; 95% CI 0.65 to 0.87).
metformin 1281 nonusers among colorectal cancers with diabetes was noted (HR 0.75; 95% CI 0.65 to 0.87). However, metformin reveals no benefits for cancer-specific survival (HR 0.79, 95%, CI 0.58 to 1.08). Conclusions. Metformin
metformin 2831 associated with higher cancer mortality, researchers have investigated if antidiabetic medications such as metformin would modify the negative effect. Preclinical studies found that metformin reduces insulin and IGF-1
metformin 2906 antidiabetic medications such as metformin would modify the negative effect. Preclinical studies found that metformin reduces insulin and IGF-1 level in serum and stables blood glucose level through AMPK pathway and thus
metformin 3367 the overall survival (OS) [[16]–[18]]. However, some studies did not find any associations between metformin use and the OS of CRC patients [[19]–[21]].The relationship between metformin use and the prognosis
metformin 3447 associations between metformin use and the OS of CRC patients [[19]–[21]].The relationship between metformin use and the prognosis of CRC patients with diabetes is still controversial according to the current
metformin 3594 with diabetes is still controversial according to the current results. In order to clarify whether metformin improves the survival of diabetic CRC patients, we conducted the meta-analysis.2. Methods2.1. Search
metformin 5109 subgroup and 5-year survival rate or any data that could be used to estimate HRs; (3) diabetes and metformin use being identified prior to colorectal cancer diagnosis. Exclusion criteria were as follows: (1) case
metformin 5266 diagnosis. Exclusion criteria were as follows: (1) case control studies; (2) less than 6 months of metformin use; (3) median follow-up time less than 3 years.Two independent investigators (Li Song and Fanqiang
metformin 5792 and country; (2) mean age, tumor stage, or gender composition; (3) number of patients with or without metformin use; (4) OS or cancer-specific mortality and adjusted HRs with their 95% CIs.2.3. Quality AssessmentNewcastle-Ottawa
metformin 7516 on OS and cancer-specific mortality among colorectal cancer patients with diabetes mellitus who take metformin or other methods to control blood sugar level. The 7 studies were all cohort studies, most of which
metformin 8072 proportional hazard model, logistic regression model, or Kaplan-Meier were employed to analyze the effect of metformin use on CRC patients. Different confounding variables were adjusted in each study (mainly age, tumor
metformin 8262 (mainly age, tumor stage, tumor grade, year of diagnosis, comorbidity, aspirin use, exposure to non metformin ADDs, socioeconomic status, radiation therapy, sex, type of tumor, chemotherapy, ASA score, blood transfusion,
metformin 8819 Survival Outcomes of Colorectal Cancer with DiabetesThe estimated HRs for association between exposure to metformin and colorectal cancer survival were shown in Figure 2 (see Figure 2). The Forest plot in Figure 2 portrays
metformin 9389 survival benefit, while the pooled results (HR 0.79; 95% CI 0.69 to 0.91) revealed an improved OS for metformin users over nonusers among colorectal cancers with diabetes. Of the 7 studies included, 4 reported cancer-specific
metformin 9680 to 1.38 with the pooled results (HR 0.79; 95% CI 0.58 to 1.08) (see Figure 3). Our study shows that metformin use in colorectal cancer patients with diabetes improved OS, reduced cancer-specific mortality, but
metformin 10426 substantial impact on the pooled-effect estimates.4. DiscussionOur meta-analysis evaluates whether metformin would affect the prognosis of diabetic colorectal cancer patients. Seven cohort studies were included
metformin 10573 diabetic colorectal cancer patients. Seven cohort studies were included in our analysis. We found that the metformin group has a prolonged OS over nonusers with a pooled HR of 0.75 (95% CI 0.65 to 0.87). Four out of seven
metformin 10763 0.87). Four out of seven studies conducted a pooled analysis of cancer-specific mortality. However, metformin reveals no benefits for colorectal cancer patients with diabetes mellitus in further analysis (HR 0.79,
metformin 10930 diabetes mellitus in further analysis (HR 0.79, 95% CI 0.58 to 1.08).The association among diabetes, metformin , and colorectal cancer has been widely explored. In Luo et al.'s [[9]] and Guraya's [[26]] meta-analyses,
metformin 11289 Similarly, diabetic CRC patients tend to have a worse prognosis [[10]]. Many studies have found that metformin , a basic antidiabetic medication, could reduce CRC incidence [[27], [28]]. Metformin decreases insulin
metformin 11781 plays a critical role in cancer progression [[29]]. The inhibition of mTOR provides a rationale for metformin to suppress tumor growth. Moreover, metformin antitumor mechanisms include its cytotoxic effect on cancer
metformin 11827 [[29]]. The inhibition of mTOR provides a rationale for metformin to suppress tumor growth. Moreover, metformin antitumor mechanisms include its cytotoxic effect on cancer stem cells and synergist effect with chemotherapeutic
metformin 12044 chemotherapeutic drugs [[30], [31]].Our meta-analysis shows that CRC patients with diabetes will benefit from metformin in terms of OS but not CRC-specific survival (CS). In a previous meta-analysis of six cohort studies
metformin 12170 but not CRC-specific survival (CS). In a previous meta-analysis of six cohort studies by Mei et al., metformin group had a better OS (HR 0.56, 95% CI 0.41–0.77) and a better CS (HR 0.66, 95% CI 0.50–0.87) than
metformin 12427 confirmed in another pooled analysis by He et al., but they did not analyze the relationship between metformin and CRC-specific mortality [[28]]. Compared with the two previous studies, we exclude meeting abstracts
metformin 12797 which may explain the result difference among the three meta-analyses. In our analysis, the result that metformin decreases only all-cause mortality but not CRC-specific mortality could be explained by metformin decreasing
metformin 12895 that metformin decreases only all-cause mortality but not CRC-specific mortality could be explained by metformin decreasing diabetes-specific and cardiovascular-specific mortality in CRC patients [[33]].Our analysis
metformin 13302 conducted, showing that removing any of the seven studies would not affect the association between metformin and OS of diabetic CRC patients.Our study has several limitations. First, we did not analyze whether
metformin 13416 OS of diabetic CRC patients.Our study has several limitations. First, we did not analyze whether non metformin antidiabetic medications influence the survival of diabetic CRC patients. Given that diabetic patients
metformin 13601 Given that diabetic patients may take more than one medication to control blood glucose level or use metformin and insulin or insulin analogs at the same time, there may exist some cofounding factors. Compared with
metformin 13715 insulin or insulin analogs at the same time, there may exist some cofounding factors. Compared with metformin users, more nonmetformin users may take insulin to control glucose level. Diabetic patients using insulin
metformin 13740 analogs at the same time, there may exist some cofounding factors. Compared with metformin users, more non metformin users may take insulin to control glucose level. Diabetic patients using insulin are considered to be
metformin 14292 the meta-analysis did not give details about how long or how many pills a day the participants take metformin . Therefore, we could not evaluate whether a dose-dependent benefit exists. Third, tumor stage is an
metformin 14635 studies included stage I~IV patients. Most researches do not provide more specific data about how much metformin affects diabetic patients with early, advanced, or metastatic stages, respectively, so the analysis
metformin 14748 affects diabetic patients with early, advanced, or metastatic stages, respectively, so the analysis of metformin effect in different tumor stages is impossible. Fourth, the two studies with most participants did not
metformin 14891 is impossible. Fourth, the two studies with most participants did not show the protective effect of metformin among CRC patients, even though sensitivity analysis was conducted. Zanders et al. [[20]] and Mc Menamin
metformin 15224 this topic. Moreover, some confounding variables such as physical activity, BMI, and exposure to non metformin ADDs were not well adjusted for included studies. Finally, all the studies included were observational
metformin 15455 have methodical shortcomings and are prone to time-related biases. This may overestimate the effect of metformin among diabetic CRC patients.In conclusion, our meta-analysis shows that metformin, the commonly used
metformin 15537 overestimate the effect of metformin among diabetic CRC patients.In conclusion, our meta-analysis shows that metformin , the commonly used antidiabetic medication, prolongs the overall survival of diabetic CRC patients,
metformin 16030 1Flow diagram of studies included in the meta-analysis.Figure 2Forest plot of the association between metformin use and colorectal cancer OS.Figure 3Forest plot of the association between metformin use and cancer-specific
metformin 16116 association between metformin use and colorectal cancer OS.Figure 3Forest plot of the association between metformin use and cancer-specific mortality.Figure 4Funnel plot analysis to detect publication bias.Figure 5Sensitivity
metformin 17263 tumor stage, 3: tumor grade, 4: year of diagnosis, 5: comorbidity, 6: aspirin use, 7: exposure to non metformin ADDs, 8: socioeconomic status, 9: radiation therapy, 10: sex, 11: type of tumor, 12: chemotherapy, 13:
Select Disease Character Offset Disease Term Instance
diabetes mellitus 1549 not affect the CRC-specific survival. Metformin may be a good choice in treating CRC patients with diabetes mellitus in clinical settings.1. IntroductionColorectal cancer (CRC) is the third most commonly diagnosed cancer
diabetes mellitus 2130 diagnosis and timely and proper treatment, while heavy alcohol consumption [[3]], obesity [[4], [5]], and diabetes mellitus [[6]–[8]] are recognized as negative prognostic factors. Diabetic population has a higher risk of
diabetes mellitus 7489 These studies provided data on OS and cancer-specific mortality among colorectal cancer patients with diabetes mellitus who take metformin or other methods to control blood sugar level. The 7 studies were all cohort studies,
diabetes mellitus 10829 cancer-specific mortality. However, metformin reveals no benefits for colorectal cancer patients with diabetes mellitus in further analysis (HR 0.79, 95% CI 0.58 to 1.08).The association among diabetes, metformin, and colorectal
diabetes mellitus 15814 Metformin may be a better choice than other antidiabetic medications when treating CRC patients with diabetes mellitus . However, further studies, especially well-designed cohort studies or RCTs, are expected.Figure 1Flow
hyperglycemia 3086 level through AMPK pathway and thus reverses the tumor promoting effect driven by hyperinsulinemia and hyperglycemia [[10], [12]–[15]]. In clinical settings, some studies showed a protective role in terms of decreasing
hyperglycemia 11079 explored. In Luo et al.'s [[9]] and Guraya's [[26]] meta-analyses, the increased CRC risk is due to hyperglycemia , hyperinsulinemia, and high IGF-1 levels, which are common in diabetic patients [[13]–[15]]. Similarly,
hyperinsulinemia 3065 stables blood glucose level through AMPK pathway and thus reverses the tumor promoting effect driven by hyperinsulinemia and hyperglycemia [[10], [12]–[15]]. In clinical settings, some studies showed a protective role in
hyperinsulinemia 11094 Luo et al.'s [[9]] and Guraya's [[26]] meta-analyses, the increased CRC risk is due to hyperglycemia, hyperinsulinemia , and high IGF-1 levels, which are common in diabetic patients [[13]–[15]]. Similarly, diabetic CRC
obesity 2106 patients include early diagnosis and timely and proper treatment, while heavy alcohol consumption [[3]], obesity [[4], [5]], and diabetes mellitus [[6]–[8]] are recognized as negative prognostic factors. Diabetic

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