Retrospective Cohort Study To Determine The Effect Of Metformin And Other Factors On Survival Of Diabetic Patients With Pancreatic Adenocarcinoma

Background:Pancreatic cancer is the sixth most common cause of cancer death in China.Epidemiological data shows that the prognosis of pancreatic cancer remains extremely poor with survival rates of 24%and 5%in 1 and 5 years,respectively.Many patients with pancreatic cancer have a history of diabetes and are treated with various antidiabetic regimens.In multiple preclinical and retrospective studies,metformin has been associated with decreased risk of cancer and cancer-related mortality.But the reslts haven’t been proved by randomized controlled trials,further studies should be taken place to determine the effect of metformin on pancreatic cancer.Objective:To determine the effect of metformin and other prognostic factors on survival of diabetic patients with pancreatic adenocarcinoma.Methods:We conducted a retrospective cohort study to examine the survival benefit of metformin in diabetic patients with pancreatic cancer at Sir Run Run Shaw Hospital(SRRSH)from August 1st,2013 to July 31st,2016.A dataset of 87 patients who carried the diagnosis of "Diabetes Mellitus" and "Pancreatic Cancer" at SRRSH were screened for this study.Descriptive analysis includes distribution of pertinent variables(such as age,gender,CA199 level,BMI,smoking history,alcohol consumption,tumor site,tumor size,cancer treatment,diabetic regimen)in each cohort(metformin vs.no metformin).Kaplan-Meier product limit was used to estimate the overall survival curves.Comparison of survival curve between the two groups was made using a log-rank test.Univariate and multivariate Cox proportional hazard regression model was used to evaluate prognostic factors on the survival.Results:Mean age of patients at diagnosis of cancer was 64.48±7.33 years(range 48-82).The majority of the patients were male(59.77%).Overall 6-month,1-year and 3-year survival rates for all stages combined were 58.62%,34.48%and 6.90%,respectively.The use of insulin and metformin in the antidiabetic regimen is 40.23%and 20.69%,respectively.Metformin use wasn’t associated in risk of death(Exp(B):0.837;95%CI:0.242-2.891).Conclusion:Our study suggests that earlier stage,surgery and chemotherapy may improve the outcome in diabetic patients with pancreatic cancer independently of other known prognostic factors.This retrospective,observational cohort study showed no association between the use of metformin and overall survival in patients with pancreatic cancer,which may be associated with small sample size,the low metformin concentrations in the blood and short follow-up time.The effect of metformin on the prognosis of patients with pancreatic cancer with diabetes mellitus can be further clarified by expand the sample size,carrying out multicenter studies,gathering statistics the dose and duration of metformin,prolonging the follow-up time.