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.

Metformin (MTF) occupies a major and fundamental position in the therapeutic management of type 2 diabetes mellitus (T2DM). Gender differences in some effects and actions of MTF have been reported. Women are usually prescribed lower MTF doses compared to men and report more gastrointestinal side effects. The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, most robust meta-analyses have yet to confirm such beneficial effects.

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.

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.

Social jetlag, the misalignment between internal circadian rhythms and socially imposed schedules, is increasingly recognized as a risk factor for metabolic disorders such as obesity, type 2 diabetes (T2D), and cardiovascular disease. Recent evidence implicates the gut microbiota as a key mediator in this relationship, operating through a microbiota–gut–metabolic axis that influences host metabolism, immune function, and circadian regulation. Mechanistic studies reveal that social jetlag disrupts microbial rhythmicity, reduces short-chain fatty acid (SCFA) production, impairs intestinal barrier function, and promotes systemic inflammation, which contribute to insulin resistance and metabolic dysfunction. Clinical and preclinical interventions, including time-restricted feeding (TRF)/time-restricted eating (TRE), probiotics or melatonin supplementation, and fecal microbiota transplantation (FMT), demonstrate the potential to restore microbial and metabolic homeostasis by realigning host and microbial rhythms. This review synthesizes mechanistic insights with emerging human and clinical evidence, highlighting the gut microbiota as a novel target for chronotherapeutic strategies aimed at mitigating the metabolic consequences of circadian disruption. Recognizing and treating circadian–microbiome misalignment may provide a clinically actionable pathway to prevent or reverse chronic metabolic diseases in modern populations.