***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 : To compare the risks of short-term and long-term use of an etonogestrel-containing and ethinylestradiol-containing vaginal ring and combined oral contraceptive pills ( OCPs ) in a routine clinical study population . METHODS : This was a prospect i ve , controlled , noninterventional cohort study performed in the United States and five European countries with the following two cohorts : new users of the vaginal ring and new users of combined OCPs ( starters , switchers , or restarters ) . The study population included 33,295 users of the vaginal ring or combined OCPs recruited by 1,661 study centers . Follow-up of study participants occurred for 2 to 4 years . Main clinical outcomes of interest were cardiovascular outcomes , particularly venous and arterial thromboembolism . These outcomes were vali date d by attending physicians and further adjudicated by an independent board . Comprehensive follow-up ensured low loss to follow-up . Statistical analyses were based on Cox regression models . Primary statistical variable was the venous thromboembolic hazard ratio ( HR ) for the vaginal ring compared with combined OCPs . RESULTS : Study participants were followed-up for 66,489 woman-years . Loss to follow-up was 2.9 % . The venous thromboembolism incidence rates for the vaginal ring users and combined OCPs users were 8.3 and 9.2 per 10,000 woman-years , respectively . Cox regression analysis yielded crude and adjusted HRs for the vaginal ring users compared with combined OCPs users of 0.9 and 0.8 for venous thromboembolism ( 95 % confidence intervals [ CIs ] 0.5–1.6 and 0.5–1.5 ) and 0.8 and 0.7 ( 95 % CIs 0.2–2.5 and 0.2–2.3 ) for arterial thromboembolism , respectively . CONCLUSION : Vaginal ring use and combined OCP use were associated with a similar venous and arterial thromboembolic risk during routine clinical use . LEVEL OF EVIDENCE : 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 There is growing evidence that patients with type 2 diabetes mellitus have increased  cancer risk . We examined the association between diabetes , cancer , and cancer-related mortality  and hypothesized that insulin sensitizers lower cancer-related mortality . Participants in the Diabetes Cardiovascular Risk and Evaluation : Targets and Essential Data for Commitment of Treatment study , a nationwide cross-sectional and prospect i ve epidemiological study , were recruited from German primary care practice s. In the cross-sectional study , subjects with type 2 diabetes mellitus had a higher prevalence of malignancies ( 66/1308 , 5.1 % ) compared to nondiabetic subjects ( 185/6211 , 3.0 % ) ( odds ratio , 1.64 ; 95 % confidence interval , 1.12 - 2.41 ) before and after adjustment for age , sex , hemoglobin A(1c ) , smoking status , and body mass index . Patients on  metformin had a lower prevalence of malignancies , comparable with that among nondiabetic patients , whereas those on any other oral combination treatment had a 2-fold higher risk for malignancies even after adjusting for possible confounders ; inclusion of metformin in these regimens decreased the prevalence of malignancies . In the prospect i ve analyses , diabetic patients in general and diabetic patients treated with insulin ( either as monotherapy or in combination with other treatments ) had a 2- and 4-fold , respectively , higher mortality rate than nondiabetic patients , even after adjustment for potential confounders ( incidence of cancer deaths in patients with type 2 diabetes mellitus [ 2.6 % ] vs the incidence of cancer deaths in patients without type 2 diabetes mellitus [ 1.2 % ] ) . Our results suggest that diabetes and medications for diabetes , with the exception of the insulin sensitizer metformin , increase cancer risk and mortality Background : Experimental studies have suggested that metformin may decrease the incidence of colorectal cancer in patients with type II diabetes . However , previous observational studies have reported contradictory results , which are likely due to important method ologic limitations . Thus , the objective of this study was to assess whether the use of metformin is associated with the incidence of colorectal cancer in patients with type II diabetes . Methods : A cohort study of patients newly treated with non-insulin antidiabetic agents  was assembled using the United Kingdom Clinical Practice Research Data link . A nested case – control analysis was conducted , where all incident cases of colorectal cancer occurring during follow-up were identified and r and omly matched with up to 10 controls . Conditional logistic regression was used to estimate adjusted rate ratios ( RR ) of colorectal cancer associated with ever use , and cumulative duration of use of metformin . All models accounted for latency and were adjusted for relevant potential confounding factors . Results : Overall , ever use of metformin was not associated with the incidence of colorectal cancer [ RR : 0.93 ; 95 % confidence interval ( CI ) , 0.73–1.18 ] . Similarly , no dose – response relationship was observed in terms of cumulative duration of use . Conclusions : The use of metformin was not associated with the incidence of colorectal cancer in patients with type II diabetes . Impact : The results of this study do not support the launch of metformin r and omized controlled trials for the chemoprevention of colorectal cancer . Cancer Epidemiol Biomarkers Prev ; 22(10 ) ; 1877–83 . © 2013 AACR Aims /hypothesis Studies on the link between diabetes and bladder cancer in Asians are rare . We investigated the association between diabetes and incidence of bladder cancer by using a large national insurance data base . Methods A r and om sample of 1,000,000 individuals covered by the National Health Insurance was recruited . A total of 495,199 men and 503,748 women for all ages and 187,609 men and 189,762 women ≥40 years old and without bladder cancer at recruitment were followed from 2003 to 2005 . Cox regression evaluated the adjusted relative risk for all ages and for age ≥40 years old . Results The results were similar for all ages and for age ≥40 years . In Cox models , patients with diabetes consistently showed a significantly higher relative risk ranging from 1.36 to 1.51 after adjustment for age , sex and other potential confounders . Age , male sex , nephropathy , urinary tract diseases ( infection and stone ) and statin use were associated with bladder cancer , but occupation , hypertension , stroke , ischaemic heart disease , peripheral arterial disease , eye disease , dyslipidaemia and medications ( oral glucose-lowering agents including sulfonylurea , metformin , acarbose and thiazolidinediones , insulin , fibrates , ACE inhibitors/angiotensin receptor blockers and calcium channel blockers ) were not . Chronic obstructive pulmonary disease and living in regions other than Metropolitan Taipei were associated with lower risk . Conclusions Patients with diabetes have a higher risk of bladder cancer . The association with urinary tract diseases suggests a complex scenario in the link between bladder cancer and diabetes at different disease stages INTRODUCTION The prevalence of type 2 diabetes in Thail and is 9.8 percent which is double the number forecast by World Health Organization . There is inadequate information to statistically represent all Thai diabetic patients for their causes of death . OBJECTIVE To determine the clinical characteristics that predicted death and causes of death in Thai diabetic patients . MATERIAL AND METHOD This prospect i ve cohort was a 3-year follow-up study of the Thai Diabetes Registry project done between April , 2003 , and February , 2006 , which registered 9,419 diabetic patients attending 11 diabetic clinics in tertiary medical centers in Bangkok and major provinces of Thail and . The dead or alive status ( 99.5 % ) was determined . The causes of death were defined by review ing the medical records . RESULTS Of the 9,370 diabetic patients registered , 425 patients  died , 1.84 percent per year . There was an increased risk of death associated with age , type of healthcare plan , lower education , insulin use , smoking , history of coronary artery disease and cerebrovascular disease , serum creatinine and high HbA1c . Lipid-lowering medication and metformin decreased the risk of death . Cardiovascular disease , infection and cancer were the prevalent causes of death . CONCLUSION The present study showed risk factors that influenced death and causes of death in Thai diabetics BACKGROUND In the 2.8 years of the Diabetes Prevention Program ( DPP ) r and omised clinical trial ,  diabetes incidence  in high-risk adults was reduced by 58 % with intensive lifestyle intervention and by 31 % with metformin , compared with placebo . We investigated the persistence of these effects in the long term . METHODS All active DPP participants were eligible for continued follow-up . 2766 of 3150 ( 88 % ) enrolled for a median additional follow-up of 5.7 years ( IQR 5.5 - 5.8 ) . 910 participants were from the lifestyle , 924 from the metformin , and 932 were from the original placebo groups .  On the basis of the benefits from the intensive lifestyle intervention in the DPP , all three groups were offered group-implemented lifestyle intervention . Metformin treatment was continued in the original metformin group ( 850 mg twice daily as tolerated ) , with participants unmasked to assignment , and the original lifestyle intervention group was offered additional lifestyle support . The primary outcome was development of diabetes according to American Diabetes Association criteria . Analysis was by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT00038727 . FINDINGS During the 10.0-year ( IQR 9.0 - 10.5 ) follow-up since r and omisation to DPP , the original lifestyle group lost , then partly regained weight . The modest weight loss with metformin was maintained . Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years ( 95 % CI 4.1 - 5.7 ) in the intensive lifestyle intervention group , 7.8 ( 6.8 - 8.8 ) in the metformin group , and 11.0 ( 9.8 - 12.3 ) in the placebo group . Diabetes incidence rates in this follow-up study were similar between treatment groups : 5.9 per 100 person-years ( 5.1 - 6.8 ) for lifestyle , 4.9 ( 4.2 - 5.7 ) for metformin , and 5.6 ( 4.8 - 6.5 ) for placebo . Diabetes incidence in the 10 years since DPP r and omisation was reduced by 34 % ( 24 - 42 ) in the lifestyle group and 18 % ( 7 - 28 ) in the metformin group compared with placebo . INTERPRETATION During follow-up after DPP , incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group , but the cumulative incidence of diabetes remained lowest in the lifestyle group . Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases 
    Output:
    
The apparent reductions in all-cause mortality and diseases of ageing associated with metformin use suggest that metformin could be extending life and healthspans by acting as a geroprotective agent