***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase ( AMPK ) . Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels . We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes . RESEARCH DESIGN AND METHODS In an observational cohort study using record-linkage data bases and based in Tayside , Scotl and , U.K. , we identified people with type 2 diabetes who were new users of metformin in 1994–2003 . We also identified a set of diabetic comparators , individually matched to the metformin users by year of diabetes diagnosis , who had never used metformin . In a survival analysis we calculated hazard ratios for diagnosis of cancer , adjusted for baseline characteristics of the two groups using Cox regression . RESULTS Cancer was diagnosed among 7.3 % of 4,085 metformin users compared with 11.6 % of 4,085 comparators  , with median times to cancer of 3.5 and 2.6 years , respectively ( P < 0.001 ) . The unadjusted hazard ratio ( 95 % CI ) for cancer was 0.46 ( 0.40–0.53 ) . After adjusting for sex , age , BMI , A1C , deprivation , smoking , and other drug use , there was still a significantly reduced risk of cancer associated with metformin : 0.63 ( 0.53–0.75 ) . CONCLUSIONS These results suggest that metformin use may be associated with a reduced risk of cancer . A r and omized trial is needed to assess whether metformin is protective in a population at high risk for cancer OBJECTIVE The Treatment Options for type 2 Diabetes in Adolescents and Youth ( TODAY ) trial demonstrated that combination therapy with metformin plus rosiglitazone provided superior durability of glycemic control compared with metformin alone , with significantly lower treatment failure rates ( 38.6 vs. 51.7 % ) , and metformin plus lifestyle was intermediate . Herein we describe the temporal changes in measures of β-cell function and insulin sensitivity over a 4-year period among the three treatments . RESEARCH DESIGN AND METHODS TODAY participants ( 699 ) were tested periodically with an oral glucose tolerance test to determine insulin sensitivity ( 1/fasting insulin [ 1/IF ] ) , insulinogenic index ( △ I30/ △ G30 ) or C-peptide index ( △ C30/ △ G30 ) , and β-cell function relative to insulin sensitivity ( oral disposition index [ oDI ] ) . RESULTS During the first 6 months , metformin plus rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and oDI versus metformin alone and versus metformin plus lifestyle ; these improvements were sustained over 48 months of TODAY . Irrespective of treatment , those who failed to maintain glycemic control had significantly lower β-cell function ( ∼50 % ) , higher fasting glucose concentration , and higher HbA1c at r and omization compared with those who did not fail . CONCLUSIONS The beneficial change in insulin sensitivity and the result ant lower burden on β-cell function achieved in the first 6 months with metformin plus rosiglitazone appear to be responsible for its superior glycemic durability  over metformin alone and metformin plus lifestyle . However , initial β-cell reserve and HbA1c at r and omization are independent predictors of glycemic durability . Therefore , efforts to preserve β-cell function before significant loss occurs and to reduce HbA1c may be beneficial in the treatment of youth with type 2 diabetes Locally advanced rectal cancer is commonly treated with chemoradiation prior to total mesorectal excision ( TME ) . Studies suggest that metformin may be an effective chemopreventive agent in this disease as well as a possible adjunct to current therapy . In this study , we examined the effect of metformin use on pathologic complete response ( pCR ) rates and outcomes in rectal cancer . The charts of 482 patients with locally advanced rectal adenocarcinoma treated from 1996 to 2009 with chemoradiation and TME were review ed . Median radiation dose was 50.4 Gy ( range 19.8–63 ) . Nearly , all patients were treated with concurrent 5‐fluorouracil‐based chemotherapy ( 98 % ) followed by adjuvant chemotherapy ( 81.3 % ) . Patients were categorized as nondiabetic ( 422 ) , diabetic not taking metformin ( 40 ) , or diabetic taking metformin  ( 20 ) . No significant differences between groups were found in clinical tumor classification , nodal classification , tumor distance from the anal verge or circumferential extent , pretreatment carcinoembryonic antigen level , or pathologic differentiation . pCR rates were 16.6 % for nondiabetics , 7.5 % for diabetics not using metformin , and 35 % for diabetics taking metformin , with metformin users having significantly higher pCR rates than either nondiabetics ( P = 0.03 ) or diabetics not using metformin ( P = 0.007 ) . Metformin use was significantly associated with pCR rate on univariate ( P = 0.05 ) and multivariate ( P = 0.01 ) analyses . Furthermore , patients taking metformin had significantly increased disease‐free ( P = 0.013 ) and overall survival ( P = 0.008 ) compared with other diabetic patients . Metformin use is associated with significantly higher pCR rates as well as improved survival . These promising data warrant further prospect i ve study BACKGROUND Recent studies have suggested an effect of metformin on mortality for patients with both diabetes and colorectal cancer ( crc ) . However , the literature is contradictory , with both positive and negative effects being identified . We set out to determine the effect of metformin with respect to prognosis in crc patients . METHODS After a retrospective chart review of crc patients treated at the Cancer Centre of Southeastern Ontario , Kaplan-Meier analyses and Cox proportional hazards regression models were used to compare overall survival ( os ) in patients with and without diabetes . RESULTS We identified 1304 crc patients treated at the centre . No significant differences between the diabetic and nondiabetic groups were observed with respect to tumour pathology , extent of metastatic disease , time or toxicity of chemotherapy , and the os rate ( 1-year os : 85.6 % vs. 86.4 % , p = 0.695 ; 2-year os : 73.6 % vs. 77.0 % , p = 0.265 ) . In subgroup analysis , diabetic patients taking metformin  survived significantly longer than their counterparts taking other diabetes treatments ( os for the metformin group : 91 % at 1 year ; 80.5 % at 2 years ; os for the group taking other treatments , including diet control : 80.6 % at 1 year , 67.4 % at 2 years ) . Multivariate analysis suggests that patients with diabetes taking treatments other than metformin experience worse survival ( p = 0.025 ) . CONCLUSIONS Our results suggest that crc patients with diabetes , excluding those taking metformin  , might have a worse crc prognosis . Taking metformin appears to have a positive association with prognosis . The protective nature of metformin needs further evaluation in prospect i ve analyses 
    Output:
    
Our findings suggest that metformin intake is associated with improved survival outcomes in terms of OS and CS in CRC patients with diabetes , particular for OS in stage II and stage III patients .