This retrospective cohort study aimed to analyze overall and cause-specific mortality risk in people with type 2 diabetes mellitus (T2DM) in Lithuania. Information on the diagnosis of T2DM and glucose-lowering medication was obtained from the National Health Insurance Fund database, causes of death–from death certificates. Sex, age, and calendar period-standardized mortality ratios (SMRs) were calculated. In addition, 89,512 patients were followed-up between 2010 and 2017, contributing to the observation period of 592,321 person-years. Overall mortality risk was increased for both sexes (overall SMR = 1.35, 95% confidence interval (CI) 1.34–1.37). Greatest mortality risk was in the age group of 40–49 years at diabetes diagnosis (SMR = 1.68, 95% CI 1.60–1.76) and among those who had died before the age of 50 (SMR = 22.04, 95% CI 18.82–25.81). Patients treated with insulin only had the highest SMR (2.43, 95% CI 2.32–2.55). Mortality risk increased with increasing diabetes duration and was higher in women in all these groups. The highest cause-specific SMRs were infection-related causes (SMR = 1.44), particularly septicemia (SMR = 1.78), diseases of the circulatory system (SMR = 1.42), especially ischemic heart (SMR = 1.46) and cerebrovascular diseases (SMR = 1.38), as well as diseases of the digestive system (SMR = 1.35). Cancer mortality risk was elevated for women (SMR = 1.13), but not for men (SMR = 0.93). In conclusion, people with T2DM had an excess mortality risk, which was higher in women compared to men, younger people, in those who were diagnosed with T2DM at a younger age, had longer diabetes duration, and who required treatment with insulin.

A retrospective cohort design was used with the objective to evaluate cancer risk among people with type 2 diabetes mellitus (T2DM) in Lithuania. The cohort was established by identifying all patients with the first diagnosis of T2DM in the National Health Insurance Fund database during 2000–2012. Cancer cases were identified by record linkage with the Lithuanian Cancer Registry. Standardized incidence ratios (SIRs) were calculated. Of the 127,290 people that were included, 5959 cases of cancer in men and 6661 cancer cases in women with T2DM were observed. A statistically significant increase in risk for all cancer sites was observed in women, SIR 1.16 (95% CI 1.14–1.19), but not in men, SIR 1.00 (95% CI 0.98–1.03). Among males, a significant increase of liver (SIR 2.11, 95% CI 1.79–2.49]), pancreas (SIR 1.77, 95% CI 1.57–1.99), kidney (SIR 1.46 95% CI 1.31–1.62), thyroid (SIR 1.83, 95% CI 1.32–2.54), colorectal (SIR 1.23, 95% CI 1.14–1.31]), skin melanoma (SIR 1.40, 95% CI 1.11–1.76), and non–melanoma skin (SIR 1.14, 95% CI 1.05–1.23) cancer was observed. For females with T2DM, a significant increase in risk of cancer of the liver (SIR 1.45, 95% CI 1.17–1.79), pancreas (SIR 1.74, 95% CI 1.56–1.93), kidney (SIR = 1.43, 95% CI 1.28–1.60), thyroid (SIR = 1.40, 95% CI 1.22–1.62), breast (SIR = 1.24, 95% CI 1.17–1.31), and corpus uteri (SIR 2.07, 95% CI 1.93–2.21) was observed. In conclusion, people with T2DM in Lithuania had an increased risk of site-specific cancer.

We assessed gastric cancer risk in type 2 diabetes mellitus patients. Gastric cancer patients with diabetes between 2001–2012 were identified. Four groups were analysed: combination therapy with metformin users; insulin and other medication users; metformin and insulin users; and sulfonylurea users. Standardised incidence ratios (SIRs) for gastric cancers as a ratio of the observed number of cancer cases in people with diabetes to the expected number of cancer cases in the underlying general population were calculated. A total of 99,992 patients with diabetes were analysed and 337 gastric cancer cases in patients with diabetes were observed when compared to the expected number of 400.54 gastric cancer cases, according to the cancer rates of the general population (SIR 0.84, 95% confidence interval (CI): 0.76–0.94). Lower risk of gastric cancer was found both in male and female patients with diabetes, however, risk among females was insignificantly lower. Higher gastric cancer risk was found in the group of diabetic patients treated with sulfonylureas (SIR 1.31, 95% CI: 1.04–1.65) and significantly lower risk than expected from the general population was found in the group of metformin users (SIR 0.75, 95% CI: 0.66–0.86). Type 2 diabetes mellitus was not associated with increased risk of gastric cancer. Metformin might decrease the risk of gastric cancer in patients with diabetes, while sulfonylureas may increase gastric cancer risk.

We evaluated the effect of antihyperglycemic therapy on the survival of patients with lung cancer (LC). The analysis included patients with LC and concomitant type 2 diabetes. 15,929 patients were classified into five groups: metformin users, insulin users, metformin and insulin users, sulphonylurea users and non-diabetic group. A multivariate analysis showed that exposure to either metformin or to insulin was associated with a lower risk of LC-specific mortality, and this approached statistical significance (HR 0.82, 95% CI 0.72–92 for metformin and HR 0.65, 95% CI 0.44–95 for insulin). When deaths from all causes were considered, only metformin exposure was associated with a significantly lower risk of death (HR 0.82, 95% CI 0.73–0.92). Users of sulphonylurea were at a higher risk of LC-specific and overall mortality (HRs 1.19, 95% CI 0.99–1.43 and 1.22, 95% CI 1.03–1.45). Our study shows a positive effect of metformin on the survival of patients with LC. Moreover, our results show that exposure to insulin was associated with a lower risk of LC-specific mortality, but not with deaths from all causes. The study results suggested that users of sulphonylurea may be at a higher risk of LC-specific and overall mortality.

The aim of this study was to examine the association between type 2 diabetes (T2DM), use of glucose-lowering medications and endometrial cancer (EC) risk. Methods: The risk of EC incidence among women with T2DM in Lithuania was assessed using a retrospective cohort study design. Female patients who were registered with T2DM between 1 January 2000 and 31 December 2012 were identified in the National Health Insurance Fund database. EC cases (ICD-10 code C54) were identified from the Lithuanian Cancer Registry. Standardized incidence ratios (SIRs) were calculated by dividing the observed numbers of EC among patients with T2DM by the expected number of EC, calculated using national rates. Results: A total of 77,708 diabetic women were included in the analysis, and 995 cases of EC were identified. A significantly increased EC risk in diabetic women was found as compared to the general population (SIR = 1.69, 95% CI 1.59–1.80). The greatest EC risk was found among younger patients at T2DM diagnosis, and the risk declined gradually with increasing age but persisted in being significantly increased among all age groups. The risk for EC increased with increasing duration of diabetes, and the highest EC risk was observed more than 10 years after T2DM diagnosis. A significantly higher EC risk than expected from the general population was found in all patient groups by glucose-lowering medication combinations. The lowest EC risk was observed in diabetic women who were users of “oral only” (without metformin) (SIR = 1.42, 95% CI 1.10–1.83) and “metformin only” (SIR = 1.69, 95% CI 1.49–1.92) medications. A two times greater EC risk was observed among the remaining glucose-lowering medication categories. In contrast, use of insulin only was not related to a higher EC incidence risk (SIR = 0.45, 95% CI 0.23–0.86); however, the risk estimation was based on nine cases. Conclusions: Our study shows a significantly increased EC risk in diabetic women as compared to the general population. In this study, a significantly higher EC risk was found in all patient groups by glucose-lowering medication combinations, except for insulin only users.

Background: We assessed the association between the use of metformin and other antihyperglycemic medications on overall survival in diabetic patients with pancreatic cancer. Methods: Patients with pancreatic cancer and diabetes between 2000 and 2015 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database. Cohort members were classified into six groups according to type 2 diabetes mellitus treatment: sulfonylurea monotherapy; metformin monotherapy; insulin monotherapy; metformin and sulfonylurea combination; metformin and other antihyperglycemic medications; all other combinations of oral antihyperglycemic medications. Survival was calculated from the date of cancer diagnosis to the date of death or the end of follow-up (31 December 2018). Results: Study group included 454 diabetic patients with pancreatic cancer. We found no statistically significant differences in overall survival between patients by glucose-lowering therapy. However, highest mortality risk was observed in patients on insulin monotherapy, and better survival was observed in the groups of patients using antihyperglycemic medication combinations, metformin alone, and metformin in combination with sulfonylurea. Analysis by cumulative dose of metformin showed significantly lower mortality risk in the highest cumulative dose category (HR 0.76, 95% CI 0.58–0.99). Conclusions: Our study showed that metformin might have a survival benefit for pancreatic cancer patients, suggesting a potentially available option for the treatment.