Type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD) are not merely coexisting epidemics but co-evolving manifestations of a shared cardiometabolic continuum. Despite advances in glycemic, lipid, and blood pressure control, residual cardiovascular risk remains high, underscoring the limitations of siloed approaches. In this perspective, we argue for reframing T2D and CVD as interconnected conditions driven by inflammation, adipose tissue dysfunction, and organ crosstalk. Beyond metformin, which remains foundational, several glucose-lowering drug classes are now evaluated not only for glycemic control but also for their cardiovascular and renal impact. Landmark trials and recent meta-analyses confirm that sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists improve cardiorenal outcomes. More recently, tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, has shown unprecedented efficacy in weight and glucose management, with potential to further transform cardiometabolic risk reduction. Yet enthusiasm for these therapies must be tempered by heterogeneity of response, treatment costs, and inequitable access. Integrated care models, supported by multidisciplinary teams, digital health tools, and value-based reimbursement, are essential to close the gap between trial efficacy and real-world outcomes. Attention to sex, age, ethnicity, and comorbidity profiles is critical to ensure equity, as is the adaptation of strategies to low- and middle-income countries where the burden of cardiometabolic disease is rapidly rising. Ultimately, advancing cardiometabolic medicine requires not only novel therapies but also a unifying framework that integrates biology, behavior, economics, and health systems to deliver the right treatment to the right patient at the right time.

The transition from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) reflects a paradigm shift in hepatology and highlights the need for a more pathophysiologically based classification. The aim of this review is to critically examine the conceptual evolution from NAFLD to MASLD, highlighting the implications for pathogenesis, diagnosis, risk stratification, and therapeutic strategies within the broader context of systemic metabolic dysfunction. Unlike the exclusion-based NAFLD definition, MASLD is grounded in positive diagnostic criteria and recognizes hepatic steatosis as a manifestation of metabolic disease. This reclassification improves clinical risk assessment and aligns hepatic care with cardiometabolic management. MASLD is closely linked to insulin resistance, lipotoxicity, chronic inflammation, and gut dysbiosis, which contribute to cardiovascular disease, chronic kidney disease, type 2 diabetes, and hepatocellular carcinoma. Non-invasive tools (e.g., FIB-4, elastography, ELF score) and emerging biomarkers (e.g., miR-122, CK-18, FGF21) support early diagnosis and personalized approaches. Therapeutically, MASLD management includes lifestyle modification, antidiabetic agents (GLP-1 receptor agonists, SGLT2 inhibitors), PPAR agonists, and novel drugs such as resmetirom. This evolving framework demands integrated, multidisciplinary strategies to address the systemic burden and clinical heterogeneity of MASLD.

Metformin, a 60-year-old biguanide and cornerstone of type 2 diabetes therapy, continues to challenge and inspire modern pharmaceutical science. Despite its chemical simplicity, metformin displays highly complex pharmacokinetic and pharmacodynamic behavior driven by transporter dependence, luminal activity, and formulation-sensitive exposure. Originally regarded as limited by low permeability and incomplete absorption, metformin has emerged as a paradigm for gut-targeted therapy, controlled- and delayed-release systems, and personalized pharmaceutics. Growing evidence has repositioned the intestine, rather than systemic plasma exposure, as a major site of action, highlighting the central role of organic cation transporters and multidrug efflux systems in determining efficacy, variability, and gastrointestinal tolerability. Beyond metabolic control, insights into transporter regulation, pharmacogenetics, microbiome interactions, and manufacturing quality have expanded metformin’s relevance as a model compound for contemporary drug development. Advances in formulation design, quality-by-design manufacturing, and regulatory control have further reinforced its clinical robustness, while repurposing efforts in oncology, immunometabolism, and regenerative medicine underscore its translational potential. This review integrates mechanistic pharmacology, formulation science, and clinical translation to position metformin not merely as an antidiabetic agent, but as a didactic model illustrating the evolution of pharmaceutics from molecule-centered design to system-oriented, precision-driven therapy.

New onset diabetes after transplantation (NODAT) is one of the most common and serious complications of solid organ transplantation. The incidence of NODAT is estimated to range from 2% to 53%. Patients who develop new onset diabetes after transplantation are significantly more frequently exposed to a higher risk of death and cardiovascular incidents as well as other adverse effects, such as decreased patient survival, higher infection rates and early graft loss. Identifying high-risk patients, undertaking preventive action and applying appropriate treatment can limit the development of new onset diabetes after transplantation and improve a patient’s long-term prognosis. New onset diabetes after transplantation (NODAT) is one of the most common and serious complications of solid organ transplantation. The incidence of NODAT is estimated to range from 2% to 53%. Patients who develop new onset diabetes after transplantation are significantly more frequently exposed to a higher risk of death and cardiovascular incidents as well as other adverse effects, such as decreased patient survival, higher infection rates and early graft loss. Identifying high-risk patients, undertaking preventive action and applying appropriate treatment can limit the development of new onset diabetes after transplantation and improve a patient’s long-term prognosis.

Aim. Assessment of the effect of the physical activity level in diabetic patients on the occurrence of hypo­glycaemia. Material and methods. The survey was conducted in a group of 422 diabetic patients: 209 patients with type 1 diabetes mellitus (129 women, 80 men, mean age 30 ± 11 years, mean duration of diabetes 12 ± 8 years, HbA1c: 7.5 ± 1.4%) and 213 patients with type 2 diabetes mellitus (119 women, 94 men, mean age 60 ± 12 years, mean duration of diabetes 10 ± 9 years, HbA1c: 8 ± 1.5%). Patients filled in the questionnaire covering data on diabetes control and physical activity (based on the International Physical Activity Question­naire — IPAQ). Results. Overall the number of patients with hypogly­caemia was significantly higher in patients with high physical activity (65%) when compared to low activity (43%; p < 0.01). Patients with moderate activity did not differ from remaining groups. In type 1 diabetes mellitus number of episodes was significantly lower in low activity group (4%) when compared to high activity (61%; p < 0.001) and moderate activity (17%; p < 0.001). Also significant difference was found be­tween high and moderate activity (p < 0.001). In type 2 diabetes mellitus the relation was similar. 23% patients with hypoglycaemia in high activity; 11% in modera­te activity (p < 0.005) and 5% in low activity group (p < 0.001 vs. high and moderate activity respectively). Conclusions. The incidence of hypoglycaemia increases along with increasing physical activity. This indicates the necessity of an increased education in patients planning physical activity. (Clin Diabetol 2018; 7, 2: 108–113) Aim. Assessment of the effect of the physical activity level in diabetic patients on the occurrence of hypo­glycaemia. Material and methods. The survey was conducted in a group of 422 diabetic patients: 209 patients with type 1 diabetes mellitus (129 women, 80 men, mean age 30 ± 11 years, mean duration of diabetes 12 ± 8 years, HbA1c: 7.5 ± 1.4%) and 213 patients with type 2 diabetes mellitus (119 women, 94 men, mean age 60 ± 12 years, mean duration of diabetes 10 ± 9 years, HbA1c: 8 ± 1.5%). Patients filled in the questionnaire covering data on diabetes control and physical activity (based on the International Physical Activity Question­naire — IPAQ). Results. Overall the number of patients with hypogly­caemia was significantly higher in patients with high physical activity (65%) when compared to low activity (43%; p < 0.01). Patients with moderate activity did not differ from remaining groups. In type 1 diabetes mellitus number of episodes was significantly lower in low activity group (4%) when compared to high activity (61%; p < 0.001) and moderate activity (17%; p < 0.001). Also significant difference was found be­tween high and moderate activity (p < 0.001). In type 2 diabetes mellitus the relation was similar. 23% patients with hypoglycaemia in high activity; 11% in modera­te activity (p < 0.005) and 5% in low activity group (p < 0.001 vs. high and moderate activity respectively). Conclusions. The incidence of hypoglycaemia increases along with increasing physical activity. This indicates the necessity of an increased education in patients planning physical activity. (Clin Diabetol 2018; 7, 2: 108–113)

Cardiac allograft vasculopathy (CAV) is the leading complication limiting the long-term survival of heart transplant (HTx) patients. The goal of this study was to assess carbohydrate metabolism disorders in relation to CAV intensification in heart transplant patients according to the ISHLT grading scheme. This retrospective study involved 477 HTx recipients undergoing angiographic observation for up to 20 years after transplantation. The patients were assigned to 4 groups on the basis of their carbohydrate metabolism status: without diabetes, with type 2 diabetes prior to HTx, with new-onset diabetes after transplantation, and with transient hyperglycemia. In the study, 62.7% (n=299) of the patients manifested no diabetes after HTx, while 14.3% (n=68) of patients had type II diabetes prior to HTx and 18.4% (n=88) developed new-onset diabetes after transplantation. In total, 1442 coronary angiograms were taken in the specified control periods. CAV incidence increased over time after transplantation, reaching 11% after 1 year, 57% after 10 years, and 50% after 20 years. The longest survival time was observed for patients who had developed type II diabetes prior to HTx, but the difference was not statistically significant. The multivariate analysis failed to identify an independent risk factor for developing cardiac allograft vasculopathy. Despite the relatively high rates of CAV and carbohydrate metabolism disorders in heart transplant patients, our retrospective analysis revealed no statistically significant link between these 2 diseases.