Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysis

Existing Reviews

Please note, new claims can take a short while to show up.

No claims yet.

Annotation Summary

Term Occurence Count Dictionary
hyperinsulinemia 4 endocrinologydiseases
metabolic syndrome 1 endocrinologydiseases
metformin 67 endocrinologydiseasesdrugs
type 2 diabetes mellitus 4 endocrinologydiseases
diabetes mellitus 5 endocrinologydiseases
diabetic retinopathy 1 endocrinologydiseases
hyperglycemia 3 endocrinologydiseases

Graph of close proximity drug and disease terms (within 200 characters).

Note: If this graph is empty, then there are no terms that meet the proximity constraint.

Review

Having read the paper, please pick a pair of statements from the paper to indicate that a drug and disease are related.

Select Drug Character Offset Drug Term Instance
metformin 1061 ChinaPublication date (collection): 2/2017Publication date (epub): 12/2016AbstractRecent evidence indicates that metformin therapy may be associated with a decreased colorectal adenoma/colorectal cancer risk in type 2 diabetes
metformin 1317 consistent. We therefore performed a systematic review and meta-analysis to assess the association between metformin therapy and risk of colorectal adenomas/colorectal cancer in type 2 diabetes mellitus patients. We searched
metformin 2413 95% CI: 0.62-0.86, p=0.0002). And when the adjusted data were analyzed, colorectal cancer risk for metformin users was decreased with a reduction of 22%, compared with non-metformin users and other treatment users
metformin 2486 colorectal cancer risk for metformin users was decreased with a reduction of 22%, compared with non- metformin users and other treatment users (adjusted OR=0.78, 95% CI: 0.70–0.87, p<0.00001). Our meta-analysis
metformin 2613 treatment users (adjusted OR=0.78, 95% CI: 0.70–0.87, p<0.00001). Our meta-analysis suggested that metformin therapy may be associated with a decreased risk of colorectal adenomas and colorectal cancer in type
metformin 3617 recent studies proposed that the risk of colorectal cancer may be reduced among T2DM patients accepting metformin therapy [[4]–[6]].Metformin is a potent anti-hyperglycemic agent. It can reduce hyperinsulinemia,
metformin 3863 and lower blood glucose concentrations in T2DM patients without causing hyperglycemia [[8]]. Besides, metformin can also reduce glucose uptake from the intestinal tract, improve insulin sensitivity and utilization
metformin 4018 intestinal tract, improve insulin sensitivity and utilization by adipose tissue and skeletal muscle. Now metformin has been recommended as the first line oral therapy for newly diagnosed T2DM by many professional diabetes
metformin 4181 for newly diagnosed T2DM by many professional diabetes organizations.Some researchers indicated that metformin may be a potential protective factor of colorectal adenomas and colorectal cancer in T2DM patients.
metformin 4339 colorectal adenomas and colorectal cancer in T2DM patients. Kim et al [[9]] and Cho et al [[10]] found that metformin was independently associated with decreased colorectal adenomas incidence. Besides, Tseng et al [[11]]
metformin 4463 independently associated with decreased colorectal adenomas incidence. Besides, Tseng et al [[11]] found that metformin can reduce colorectal cancer risk (adjusted RR=0.73, 95% CI: 0.58-0.92, p=0.0115). Similar results were
metformin 4681 reported in other studies [[5], [12], [13]]. However, some other studies found no relation between metformin therapy and colorectal adenomas or colorectal cancer [[5], [9], [14], [15]], thus the results were still
metformin 5036 researchers have performed systematic reviews and meta-analysis to assess the relationship between metformin use and cancer risk, however, results refer to colorectal cancer were not consistent [[16], [17]], and
metformin 5183 refer to colorectal cancer were not consistent [[16], [17]], and the review of association between metformin therapy and colorectal adenomas risk has not been published until now. In summary, it is still inconclusive
metformin 5316 adenomas risk has not been published until now. In summary, it is still inconclusive whether use of metformin could protect T2DM patients from colorectal adenomas and colorectal cancer.To explore associations between
metformin 5433 protect T2DM patients from colorectal adenomas and colorectal cancer.To explore associations between metformin therapy and colorectal cancer and adenomas risk, we identified available studies to make a quantitative
metformin 5604 identified available studies to make a quantitative meta-analysis for the purpose of more cognition of using metformin in T2DM patients. This investigation is important to identify the existing knowledge on the effects
metformin 5717 T2DM patients. This investigation is important to identify the existing knowledge on the effects of metformin therapy in T2DM patients.RESULTSSearch resultsWe identified 759 unique papers after searching PubMed,
metformin 6804 selecting studies for meta-analysisTable 1Characteristics for publications included in the meta-analysis of metformin and colorectal adenomaFirst authoryearStudy typeRegionPeriodTreatmentControlAdjusted OR/RR, 95%CInNnNYong
metformin 7431 [[9]]2015cohortKorea2002-20128015153890.866(0.453-1.623)Table 2Characteristics for publications included in the meta-analysis of metformin and colorectal cancerFirst authoryearStudy typeRegionPeriodTreatmentControlAdjusted OR/RR/HR,95%CIAdjust
metformin 7660 Factors/CovariatesnNnNAgeSexSmokingDeprivationAlcohol useBMIHbA1COther diseaseother drugCCI scorediabetes duration metformin durationT-stageGillian Libby[[4]]2009cohortUK1994-20034040857640850.60(0.38-0.94)✓✓✓✓✓✓✓Meei-Shyuan
metformin 9454 [10]], provided sufficient data to be included in the meta-analysis to evaluate the association between metformin therapy and the risk of colorectal adenomas among T2DM patients. Table 1 shows characteristics of five
metformin 9897 site adenomas and was analyzed separately.A pooled estimate of OR and 95% CI of association between metformin therapy and colorectal adenomas among the five studies is shown in Figure 2. Metformin therapy was found
metformin 10236 heterogeneity was found (I2=34%, p=0.17) (Figure 2).Figure 2Forest plot of the association between metformin therapy and colorectal adenomasSubgroup analysis was conducted based on the type of study design. A
metformin 10930 heterogeneity was found (I2=0%, p=0.89) (Supplementary Figure 2).For we only have five studies refer to metformin therapy and colorectal adenomas risk, the number is too small to conduct the Begg's and Egger's test.
metformin 11411 cohort studies [[4], [5], [11]–[13], [18]–[22]] and one RCT [[28]]) reported the association between metformin therapy and colorectal cancer risk. Table 2 shows characteristics of all observational studies meeting
metformin 11957 summary unadjusted odds ratio with the random effects model was 0.73 (95% CI: 0.62-0.86, p=0.002) for metformin users (metformin exposure more than 1 year) compared with non-metformin users or other treatment users.
metformin 11974 odds ratio with the random effects model was 0.73 (95% CI: 0.62-0.86, p=0.002) for metformin users ( metformin exposure more than 1 year) compared with non-metformin users or other treatment users. High between-study
metformin 12029 CI: 0.62-0.86, p=0.002) for metformin users (metformin exposure more than 1 year) compared with non- metformin users or other treatment users. High between-study heterogeneity was found (I2=90%, p<0.00001) (Figure
metformin 12192 heterogeneity was found (I2=90%, p<0.00001) (Figure 3).Figure 3Forest plot of the association between metformin therapy and colorectal cancer - unadjusted odds ratiosWhen the adjusted data estimates from all observational
metformin 12366 adjusted data estimates from all observational studies were analyzed, the colorectal cancer risk for metformin users was decreased with a reduction of 22%, compared with non-metformin users or other treatment users
metformin 12439 colorectal cancer risk for metformin users was decreased with a reduction of 22%, compared with non- metformin users or other treatment users (adjusted OR=0.78, 95% CI: 0.70–0.87, p<0.00001), the between-study
metformin 12656 heterogeneity was decreased (I2=71%, p<0.00001) (Figure 4).Figure 4Forest plot of the association between metformin therapy and colorectal cancer - adjusted odds ratiosSubgroup analysis was conducted based on the type
metformin 14263 distribution of the points, suggesting a lack of publication bias (Figure 5).Figure 5Funnel plot of metformin therapy and colorectal cancer included in meta-analysisDISCUSSIONThis meta-analysis suggests that metformin
metformin 14371 metformin therapy and colorectal cancer included in meta-analysisDISCUSSIONThis meta-analysis suggests that metformin therapy may be associated with a decreased risk of colorectal adenomas (unadjusted OR=0.80, 95% CI:
metformin 14611 colorectal cancer (adjusted OR=0.70, 95% CI: 0.72-0.89, p<0.0001) among T2DM patients, compared with non- metformin users and other diabetic drug users. The degree of heterogeneity among studies may cause by the difference
metformin 14838 design, populations or comparators. However, almost all of the results showed a protective effect of metformin .Our results are consistent with previous observations suggesting a protective role of metformin for
metformin 14934 of metformin.Our results are consistent with previous observations suggesting a protective role of metformin for colorectal cancer [[16], [17], [29]]. In 2011, Zhang et al [[17]] found the metformin therapy was
metformin 15024 protective role of metformin for colorectal cancer [[16], [17], [29]]. In 2011, Zhang et al [[17]] found the metformin therapy was associated with a significantly lower risk of colorectal cancer (OR=0.63, 95% CI: 0.47-0.84,
metformin 15371 CI: 0.74–0.92, p=0.0009). However, Andrea DeCensi et al [[16]] found an inverse association between metformin use and colon cancer incidence, although not significant (SRR=0.64, 95% CI: 0.38-1.08). Similarly the
metformin 15591 study of P.D. Home [[28]], which was included in our search results, also showed no association between metformin treatment and colorectal cancer risk. These conflicting results may cause by methodological problems
metformin 15866 limit the statistical power to obtain significant results. For example, only 50 participants in the metformin group and 55 participants in the comparison group were included in the RCT study [[28]].Metformin also
metformin 16086 a protective effect in many other cancers. A meta-analysis conducted by Wu et al [[30]] showed that metformin therapy was associated with a significant reduced risk of prostate cancer among cohort studies (RR=0.92,
metformin 16302 95% CI: 0.87-0.96, p<0.001). Zhu et al [[32]] confirmed that compared with other antidiabetic drugs, metformin was significantly associated with a 16% reduction of lung cancer risk in T2DM patients (RR=0.84, 95%
metformin 16479 risk in T2DM patients (RR=0.84, 95% CI: 0.73-0.97, p=0.019). And a study by Tseng et al [[33]] proved metformin use is associated with a decreased risk of kidney cancer in patients with T2DM patients (HR=0.279, 95%
metformin 16649 patients with T2DM patients (HR=0.279, 95% CI: 0.254-0.307, p<0.0001). These studies confirmed that metformin therapy may serve as a protective factor in decreasing cancer risk.Evidences from previous studies indicate
metformin 16772 serve as a protective factor in decreasing cancer risk.Evidences from previous studies indicate that metformin may interfere with carcinogenesis through direct (insulin-independent) and indirect (insulin-dependent)
metformin 17239 hyperinsulinemia, then may reduce cancer risk among T2DM patients. Meanwhile, cell experiments show that metformin can reduce cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis
metformin 17378 increasing reactive oxygen species, which induce DNA damage and apoptosis [[37]]. Studies also found metformin can active the intracellular adenosine monophosphate-activated protein kinase (AMPK), which leads to
metformin 18364 (colorectal adenoma and colorectal cancer), which provided a stronger evidence of protective effect of metformin among T2DM patients.However, our study also has several limitations. Firstly, the selection of populations
metformin 18676 Secondly, the description of drug dose and length is unclear among studies. Most studies usually classify metformin as two groups: metformin users vs. non-users or other treatment user. And few studies collected metformin
metformin 18701 drug dose and length is unclear among studies. Most studies usually classify metformin as two groups: metformin users vs. non-users or other treatment user. And few studies collected metformin dose data. There might
metformin 18782 metformin as two groups: metformin users vs. non-users or other treatment user. And few studies collected metformin dose data. There might have a dose–response relationship between metformin use and cancer incidence
metformin 18859 few studies collected metformin dose data. There might have a dose–response relationship between metformin use and cancer incidence for T2DM patients, and we can't calculate it, which may be another large source
metformin 19107 studies. Thirdly, different adjustments may influence the summary estimation of the association between metformin treatment and colorectal adenomas/colorectal cancer risk. Furthermore, the protective effect of metformin
metformin 19213 metformin treatment and colorectal adenomas/colorectal cancer risk. Furthermore, the protective effect of metformin may be overestimated due to the association between insulin using and higher risk of colorectal cancer
metformin 19439 Future studies need to take all these factors into account and provide more precise results estimate for metformin therapy on colorectal cancer incidence.In conclusion, our meta-analysis indicates that metformin is
metformin 19536 for metformin therapy on colorectal cancer incidence.In conclusion, our meta-analysis indicates that metformin is associated with a reduction in risk of colorectal adenoma and colorectal cancer incidence in individuals
metformin 19920 cancer (due to their metabolic condition), the candidates for drug therapy may better be treated with metformin . And further prospective studies, especially large-scale clinical studies and cell experiments are needed
metformin 20095 studies and cell experiments are needed to confirm the relationship between colorectal cancers and metformin treatment.MATERIALS AND METHODSOur meta-analysis was in accordance with the Systematic Reviews and Meta-Analysis
metformin 20743 resistance“) and (“therapy” or “treatment” or “therapeutics” or “therapeutics” or “ metformin ” or “biguanides“) and ((“colorectal” or “colon” or “rectal” or “rectum“) or (“neoplasm”
metformin 21428 original article; (2) report randomized or observational studies; (3) study patients with T2DM ; (4) have metformin therapy as the first treatment (metformin exposure more than 1 year) compared with non-metformin user
metformin 21470 observational studies; (3) study patients with T2DM ; (4) have metformin therapy as the first treatment ( metformin exposure more than 1 year) compared with non-metformin user (never use metformin) and other treatments
metformin 21525 have metformin therapy as the first treatment (metformin exposure more than 1 year) compared with non- metformin user (never use metformin) and other treatments (insulin, sulfonylurea, thiazolidinedione etc.); (5)
metformin 21551 the first treatment (metformin exposure more than 1 year) compared with non-metformin user (never use metformin ) and other treatments (insulin, sulfonylurea, thiazolidinedione etc.); (5) provide relative risk (RR),
metformin 23867 used a random-effects model to estimate the pooled effect across studies for the association between metformin therapy and the risk of colorectal adenomas/colorectal cancer. For the random-effects model accounts
metformin 24230 adjusted data taken directly from the study or estimated by crude numbers for the association between metformin therapy and colorectal adenomas/colorectal cancer. Heterogeneity among studies was evaluated using I2
Select Disease Character Offset Disease Term Instance
diabetes mellitus 99 Title: OncotargetMetformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysisFeifei LiuLijing YanZhan WangYuanan LuYuanyuan ChuXiangyu
diabetes mellitus 1395 the association between metformin therapy and risk of colorectal adenomas/colorectal cancer in type 2 diabetes mellitus patients. We searched the literature published before Aug 31, 2016 in four databases: PubMed, Embase
diabetes mellitus 2726 therapy may be associated with a decreased risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients.INTRODUCTIONAccording to WHO, over 220 million people are suffering from diabetes disease.
diabetes mellitus 3064 to 472 million (9 % of the adult population) by 2025, and around 40-50% of them will develop type 2 diabetes mellitus (T2DM) [[1]]. Many studies have provided strong evidences that population with diabetes disease is at
diabetes mellitus 20593 search terms and combinations were used in keyword and subject heading search: (“diabetes” or “ diabetes mellitus ” or “DM” or “insulin resistance“) and (“therapy” or “treatment” or “therapeutics”
diabetic retinopathy 22042 of diabetes; (3) included patients with type 1 diabetes; (4) researched subjects with complication ( diabetic retinopathy etc.), hereditary colorectal syndromes, history of colorectal cancer, chronic inflammatory bowel disease,
hyperglycemia 3469 associated with T2DM [[2]] for metabolic syndromes, especially insulin resistance, hyperinsulinemia and hyperglycemia independently [[3]]. However, recent studies proposed that the risk of colorectal cancer may be reduced
hyperglycemia 3833 improve insulin resistance [[7]], and lower blood glucose concentrations in T2DM patients without causing hyperglycemia [[8]]. Besides, metformin can also reduce glucose uptake from the intestinal tract, improve insulin
hyperglycemia 16984 (insulin-dependent) mechanisms. Metabolic syndromes in T2DM patients such as insulin resistance, hyperinsulinemia and hyperglycemia are risk factors of several cancers [[2], [35], [36]]. Metformin can reduce blood glucose directly and
hyperinsulinemia 3448 cancer was also associated with T2DM [[2]] for metabolic syndromes, especially insulin resistance, hyperinsulinemia and hyperglycemia independently [[3]]. However, recent studies proposed that the risk of colorectal
hyperinsulinemia 3709 accepting metformin therapy [[4]–[6]].Metformin is a potent anti-hyperglycemic agent. It can reduce hyperinsulinemia , improve insulin resistance [[7]], and lower blood glucose concentrations in T2DM patients without causing
hyperinsulinemia 16963 indirect (insulin-dependent) mechanisms. Metabolic syndromes in T2DM patients such as insulin resistance, hyperinsulinemia and hyperglycemia are risk factors of several cancers [[2], [35], [36]]. Metformin can reduce blood
hyperinsulinemia 17134 [[2], [35], [36]]. Metformin can reduce blood glucose directly and can lower insulin resistance and hyperinsulinemia , then may reduce cancer risk among T2DM patients. Meanwhile, cell experiments show that metformin can
metabolic syndrome 3396 pancreatic and breast cancer, high incidence of colorectal cancer was also associated with T2DM [[2]] for metabolic syndrome s, especially insulin resistance, hyperinsulinemia and hyperglycemia independently [[3]]. However, recent
type 2 diabetes mellitus 92 Title: OncotargetMetformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysisFeifei LiuLijing YanZhan WangYuanan LuYuanyuan ChuXiangyu
type 2 diabetes mellitus 1388 assess the association between metformin therapy and risk of colorectal adenomas/colorectal cancer in type 2 diabetes mellitus patients. We searched the literature published before Aug 31, 2016 in four databases: PubMed, Embase
type 2 diabetes mellitus 2719 metformin therapy may be associated with a decreased risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients.INTRODUCTIONAccording to WHO, over 220 million people are suffering from diabetes disease.
type 2 diabetes mellitus 3057 increase to 472 million (9 % of the adult population) by 2025, and around 40-50% of them will develop type 2 diabetes mellitus (T2DM) [[1]]. Many studies have provided strong evidences that population with diabetes disease is at

You must be authorized to submit a review.