Search Results (341)

Background: Since the introduction of the first GLP-1 receptor agonist (GLP-1 RA) in 2005, there has been a steady increase in the number of drugs available in this group, as well as an expansion of their indications and routes of administration. Aim: The aim of the study was to assess the clinical characteristics of patients treated with GLP-1 RA in Poland in 2018–2024, with particular emphasis on the disease entities constituting indications for treatment (like obesity and diabetes), and to analyse the frequency of use of individual drugs during the study period. Methods: A cohort study was conducted based on anonymised medical data from 300 outpatient clinics the largest private healthcare facilities in Poland (Luxmed), on consecutive patients who had at least one prescription for GLP-1 RA. The analysis covered the period from 1 January 2018 to 31 December 2024. Results: The number of patients using GLP-1 RA increased from 212 in 2018 to 12,836 in 2024. Obesity was diagnosed in 78% of all patients, most often in the groups using liraglutide and tirzepatide. The highest percentage of patients with type 2 diabetes was observed in the dulaglutide group (67%), while the lowest was in the tirzepatide group (15%). From 2022, the share of oral semaglutide steadily increased, reaching 50% of all semaglutide applications in 2024 in Poland. Conclusions: In the analysed group, GLP-1 RAs were most commonly used to treat obesity. The oral form of semaglutide was more frequently used in younger females with less aggravating medical history. Full article

Background: Severe hypertriglyceridemia (SHTG) is associated with acute pancreatitis, metabolic dysfunction, and increased cardiovascular risk. Its genetic architecture ranges from rare biallelic variants causing familial chylomicronemia syndrome (FCS) to more prevalent polygenic or multifactorial chylomicronemia syndromes (MCS). Methods: We systematically reviewed scientific literature up to 2025 for studies reporting genetic data, clinical features, or therapeutic outcomes in adults with triglycerides (TG) ≥ 500 mg/dL. Extracted data were synthesized for genotype, polygenic risk score (PRS), TG levels, metabolic comorbidities, hepatic steatosis, pancreatitis, and treatment response. Results: Ten studies (n = 2521) were included. FCS due to biallelic LPL, APOC2, GPIHBP1, or LMF1 variants accounted for <5% of cases and showed extreme TG elevations (>2800 mg/dL) with pancreatitis prevalence (>70%). APOA5, APOC3, and APOB variants were associated with intermediate TG levels and high rates of metabolic dysfunction-associated steatotic liver disease (MASLD). Polygenic hypertriglyceridemia represented ~70–80% of cases, with TG ≈ 2200 mg/dL and pancreatitis prevalence 15–20%, largely modulated by metabolic triggers. MASLD was present in >70% of polygenic cases, supporting a “two-hit” model where hepatic overproduction of TG-rich lipoproteins amplifies TG excess. Interventional trials demonstrated TG reductions with APOC3 antisense therapy (70–80%) and ANGPTL3 inhibition (50–55%), while GLP-1RA significantly reduced hepatic fat (30–35%) and resolved NASH in up to 59% of patients. Conclusions: SHTG displays a genotype–phenotype gradient: FCS is linked to recurrent pancreatitis, whereas polygenic/MCS forms are closely associated with MASLD and metabolic dysfunction. These findings support a precision-medicine approach integrating genetic testing and PRS-guided strategies—prioritizing APOC3/ANGPTL3 inhibitors for FCS and combined TG-lowering plus metabolic therapies for MCS—to reduce pancreatitis recurrence and liver disease. Full article

Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant cardiometabolic benefits, particularly in patients with type 2 diabetes and obesity. Their role in heart failure (HF) is gaining increasing attention, with growing evidence supporting their efficacy in HF with preserved ejection fraction (HFpEF). Recent trials have shown that semaglutide improves symptoms, functional capacity, and weight loss in patients with HFpEF. However, these trials did not demonstrate a reduction in HF hospitalizations or mortality. In contrast, tirzepatide has revealed a significant reduction in cardiovascular death and worsening HF events in patients with obesity-related HFpEF, suggesting broader cardioprotective effects. Concordantly, the benefit of GLP1-RAs in the setting of HF with reduced ejection fraction (HFrEF) remains uncertain. Although their mechanisms suggest potential advantages, particularly for patients with a cardiometabolic phenotype, clinical evidence supporting improvements in major clinical outcomes is lacking. Additionally, concerns regarding risk of increased HF hospitalizations, fluid retention and arrhythmic risk have led to a cautious approach in this population. As HF management continues to evolve, GLP1-RAs emerge as a promising yet complex therapeutic option. This review synthesizes the current evidence, highlights key knowledge gaps, and explores how these medications might be integrated into guideline-directed medical therapy (GDMT) to determine their optimal role across the LVEF spectrum in HF. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed to treat type 2 diabetes mellitus, are now being investigated as agents in oncology. Recent preclinical studies have demonstrated their antitumor activity in several solid malignancies, including pancreatic, colorectal, breast, and prostate. Importantly, GLP-1 RAs modulate key signalling pathways such as PI3K/Akt, PKA, and AMPK, and exert anti-inflammatory effects by reducing cytokine production and macrophage infiltration. Preclinical data support their antineoplastic activity in vitro and in vivo, particularly by inhibiting tumour growth and metastasis. Nevertheless, there are ongoing concerns about tumorigenic effects in certain cancer types. This review critically examines the molecular mechanisms by which GLP-1 RAs influence cancer cell proliferation, apoptosis, angiogenesis, and inflammation, and emphasizes the need for further clinical studies to determine their therapeutic relevance. It also proposes assessing GLP-1 RAs as adjuncts in the management of solid tumours. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance, impaired insulin secretion, and chronic hyperglycemia. Recent studies have identified microRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level, as modulators of pathways involved in T2DM pathophysiology. Dysregulated miRNA expression has been detected in various samples collected from patients with T2DM, implicating these molecules in disease onset and progression. Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published from the earliest available records to 18 August 2025 using the following Boolean search terms: “miRNA AND gliclazide”, “miRNA AND glibenclamide”, “miRNA AND gliquidone”, “miRNA AND glimepiride”, “mirRNA AND metformin”, “miRNA AND pioglitazone”, “miRNA AND rosiglitazone”, “miRNA AND sitagliptin”, “miRNA AND vildagliptin”, “miRNA AND alogliptin”, “miRNA and saxagliptin”, “miRNA AND linagliptin”, “miRNA AND liraglutide”, “miRNA and dulaglutide”, “miRNA AND semaglutide”, “miRNA AND tirzepatide”, “miRNA AND lixisenatide”, “miRNA AND empagliflozin”, “miRNA AND dapagliflozin”, miRNA AND insulin glargine”, “miRNA AND insulin detemir”, “miRNA AND insulin degludec”, “miRNA AND insulin aspart”, “miRNA AND insulin glulisine”, and “miRNA AND insulin lispro”. Additionally, gray literature was searched in ClinicalTrials.gov, the EU Clinical Trials Register (EudraCT), and the ISRCTN Registry to identify unpublished studies. Studies were eligible for inclusion if they were clinical interventional studies assessing the impact of currently available antidiabetic treatments on miRNA expression. Only articles published in English were considered. The risk of bias was evaluated using the RoB2 (Risk of Bias 2) and ROBINS-I (Risk Of Bias In Non-randomized Studies—of Interventions) tools. Study characteristics and major findings were tabulated. Results: A total of 1263 manuscripts was identified initially. After removing duplicates, 726 articles remained for further screening. Ultimately, 17 manuscripts reporting interventional clinical trials on the effects of antidiabetic treatment on miRNA were included, encompassing a total of 1093 patients. Key findings included treatment-associated changes in miRNA expression and their potential utility for the prediction of clinical outcomes. Conclusions: Current evidence supports the hypothesis that antidiabetic treatments modulate miRNA expression, with some findings showing predictive value for metabolic outcomes. However, the available data remain limited and of low grade of certainty, and further large-scale clinical studies are needed to provide deeper insights into these associations. Full article

Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, and depression, are marked by progressive neuronal dysfunction and loss, yet current treatments remain largely symptomatic with limited disease-modifying efficacy. Glucagon-like peptide-1 (GLP-1), an incretin hormone traditionally associated with metabolic regulation, has emerged as a promising neuroprotective agent. Its receptor, GLP-1R, is expressed in key brain regions implicated in cognition, emotion, and motor control, including the hippocampus, frontal cortex, and substantia nigra. GLP-1R agonists (GLP-1RAs) activate multiple intracellular signaling cascades—cAMP/PKA, PI3K/Akt, and MAPK pathways—that collectively promote neuronal survival, enhance synaptic plasticity, reduce oxidative stress, inhibit apoptosis, and modulate neuroinflammation. These agents also regulate autophagy, promote remyelination, and reprogram microglial phenotypes toward anti-inflammatory states. Preclinical models have shown that GLP-1RAs reduce amyloid-β and tau pathology in AD, preserve dopaminergic neurons in PD, protect astrocytes and neural progenitors after ischemic stroke, and alleviate depressive behaviors. Notably, GLP-1RAs such as liraglutide, exenatide, and dulaglutide can cross the blood–brain barrier and have demonstrated safety and potential efficacy in early-phase clinical trials. These studies report attenuation of cortical atrophy, preservation of cerebral glucose metabolism, and improvements in quality of life, though changes in core AD biomarkers remain inconclusive. Ongoing large-scale trials (e.g., EVOKE, ELAD) are further exploring their therapeutic impact. This review consolidates the mechanistic basis and translational potential of GLP-1RAs in age-related neurodegenerative diseases, highlighting both their promise and the challenges that must be addressed in future clinical applications. Full article

Background: Oral semaglutide is the first oral GLP-1 receptor agonist approved for treating patients with type 2 diabetes mellitus (T2DM). This real-world retrospective study evaluated its effectiveness and tolerability in patients requiring a third-line antidiabetic agent due to poor glucoregulation. Methods: Adult patients with T2DM who were taking oral semaglutide and were monitored at tertiary diabetes centers in Croatia were identified through electronic medical records between October 2022 and December 2024. Patients’ data were included in the analysis if they had been on oral semaglutide for at least six months. Results: A total of 163 patients (72 females and 91 males) were recruited, with 96.9% classified as overweight or obese. Among them, 145 had a BMI greater than 30 (mean BMI: 34.18 ± 4.60). The addition of oral semaglutide to their treatment regimen resulted in significant reductions in BMI, HbA1c, and both postprandial and fasting blood glucose levels, as well as in AST and ALT levels (all p < 0.05). There was also an increase in HDL levels (p = 0.007). The side effects observed were consistent with those previously recognized. Conclusions: This study demonstrates that oral semaglutide is safe and effective for glycemic and extraglycemic management in a real-world setting when used as a third-line agent. The best outcomes in terms of weight and HbA1c reduction can be expected when it is introduced early, ideally within the first five years of diabetes duration, and particularly in patients who are insulin naive. Full article

Background: Acute kidney injury (AKI) remains a serious complication among individuals with type 2 diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed and often regarded as kidney-protective, yet post-marketing reports have linked them to AKI. Tirzepatide, a newer dual GIP/GLP-1 agonist, shows well-documented metabolic benefits, but its renal safety in real-world use is not well characterized. Methods: We conducted a disproportionality analysis of the U.S. FDA Adverse Event Reporting System (FAERS) from January 2022 to September 2025. Reporting odds ratios (RORs) and proportional reporting ratios (PRRs) were used to compare AKI reporting between tirzepatide and semaglutide. Results: Among 133,872 reports (92,807 tirzepatide; 41,065 semaglutide), AKI was listed in 432 (0.47%) and 440 (1.07%) cases, respectively. The ROR for tirzepatide versus semaglutide was 0.44 (95% CI, 0.38–0.50), suggesting a lower reporting frequency for AKI with tirzepatide. Conclusions: In this real-world pharmacovigilance analysis, semaglutide but not tirzepatide showed a disproportionality signal for AKI. While causality cannot be confirmed, clinicians should ensure hydration and renal monitoring when initiating GLP-1 RAs, particularly semaglutide. Semaglutide showed a higher AKI reporting rate than tirzepatide, though these findings should be interpreted cautiously given reporting bias and potential confounders. Both agents appear safe, with low AKI frequency in practice. Further studies should determine if differences reflect biological or reporting effects. These findings support the need for larger epidemiologic studies to define risk modifiers and optimize clinical safety strategies. Full article

Asthma and obesity are two common chronic diseases of growing clinical and social importance. One of the recognised phenotypes of asthma is obesity-related asthma, which is characterised by a more severe course, resistance to glucocorticosteroids, increased inflammation and poorer symptom control. This article discusses the complex pathophysiological mechanism of this phenotype, considering the role of chronic inflammation, immune dysregulation and metabolic disorders resulting from obesity. The potential role of glucagon-like peptide-1(GLP-1) receptor analogues as an innovative therapeutic option in the treatment of asthma in obese individuals, both with and without type 2 diabetes mellitus (T2DM), is also analysed. A literature review indicates that glucagon-like peptide-1 receptor analogue (GLP-1RA) drugs, in addition to their hypoglycaemic and weight-reducing effects, also exhibit anti-inflammatory activity in the respiratory system and may reduce the frequency of asthma exacerbations and improve asthma control. The article reviews current data from experimental and clinical studies, emphasising the need for further research on the use of GLP-1RA as an adjunct to conventional asthma therapy in the context of the obese asthma phenotype. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a transformative therapy for obesity and type 2 diabetes (T2D) in pediatric populations. This review synthesizes current evidence on efficacy, safety, and knowledge gaps in children and adolescents. Methods: A structured review of randomized controlled trials, extension studies, and mechanistic investigations evaluating GLP-1RAs in pediatric obesity and T2D was conducted. Outcomes of interest included body weight, BMI, body composition, glycemic control, and adverse events. Results: In adolescents, liraglutide and semaglutide consistently produce clinically meaningful reductions in BMI, body weight, and waist circumference, with modest improvements in systolic blood pressure and minimal effects on lipid levels or HbA1c. A newer trial in children 6 to <12 years showed liraglutide reduced BMI compared with placebo, with GI events consistent with prior safety profiles. Weight loss tends to include both fat and lean components; rapid weight loss may impair muscle strength or bone density if resistance exercise and adequate protein intake are not ensured. Risks include micronutrient gaps, misuse, and uncertain long-term effects on growth and puberty. These important considerations remain largely unaddressed in pediatric studies, and adult data can’t be directly extrapolated to children due to developmental, hormonal, and physiological differences. Conclusions: GLP-1 RAs are a promising adjunct to lifestyle therapy for pediatric obesity, but pediatric-specific protocols are needed to safeguard musculoskeletal health, ensure nutritional adequacy, and minimize misuse. Critical gaps remain in pediatric pharmacokinetics, dosing strategies, and long-term developmental safety. Further research is essential to develop evidence-based guidelines for safe and effective pediatric anti-obesity therapy. Full article

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in type 2 diabetes (T2D) management for their glycemic and weight benefits. However, their appetite-suppressing effects may influence dietary intake and nutrient adequacy, yet real-world evidence is scarce. Objective: To evaluate dietary intake and adherence to the Mediterranean diet in adults with T2D treated with GLP-1RAs compared to those receiving other oral hypoglycemic agents. Methods: In this cross-sectional study, 103 adults with T2D (mean age 66 ± 8 years; 65% male) attending a diabetes clinic in Turin, Italy, were enrolled between February and June 2025. Dietary habits were assessed using a validated food frequency questionnaire, and adherence to the Mediterranean diet was evaluated via the Mediterranean Diet Score (MDS). Anthropometric, biochemical, and lifestyle data were collected. Results: Fifty-two participants (50.5%) were treated with GLP-1RAs (semaglutide 55.8%, dulaglutide 40.4%). No significant differences in energy intake, macronutrient distribution, or MDS were observed between groups. Overall, diets were characterized by low carbohydrate intake (~44% of energy), inadequate fiber (≈11 g/1000 kcal), and high fat intake (≈39–40% of energy), with saturated fat below 10%. None of the GLP-1RA users met fiber recommendations. Subgroup analysis by treatment duration (<1 year, 1–2 years, >2 years) revealed no significant differences in dietary patterns. Conclusions: Patients with T2D, regardless of pharmacological treatment, exhibited poor adherence to dietary guidelines. These findings highlight the need for structured nutritional counseling alongside GLP-1RA therapy to optimize metabolic outcomes and prevent nutritional deficiencies. Full article

The bidirectional relationship between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) represents a critical intersection in metabolic medicine. Therefore, the present review examines the most recent data regarding molecular mechanisms linking OSA and T2DM, analyzing key biomarkers including hypoxia-inducible factors (HIF 1α), inflammatory mediators, adipokines, microRNAs, hormones, and neuropeptides that serve as both diagnostic indicators and potential therapeutic targets. Key molecular findings from the scientific literature report elevated HIF-1α promoting insulin resistance, decreased SIRT1 levels, dysregulated microRNA-181a and microRNA-199a, increased inflammatory cytokines (TNF-α, IL-6, CRP), and altered adipokine profiles with reduced adiponectin and elevated leptin and resistin. Current clinical evidence reveals significant therapeutic potential for modern antidiabetic medications in the management of OSA. GLP-1 receptor agonists, particularly tirzepatide, received FDA approval as the first medication for moderate-to-severe OSA in obese adults, showing a 55–63% AHI reduction. SGLT2 inhibitors also demonstrate promising results through weight loss and cardiovascular protection mechanisms. This integrated approach represents the evolution toward comprehensive OSA management beyond traditional mechanical ventilation strategies. Future research should focus on developing personalized treatment algorithms based on individual molecular biomarker profiles, investigating combination therapies, and exploring novel targets, including chronotherapy agents. Full article

Background/Objectives: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown blood pressure (BP) reduction in type 2 diabetes (T2D). However, head-to-head comparisons in hypertensive patients remain limited. This study assessed the effects of SGLT2i and GLP-1RA on systolic BP (SBP), diastolic BP (DBP), antihypertensive regimen modifications, and adverse events in Saudi patients with both conditions. Methods: A retrospective cohort study was conducted between January 2022 and April 2024 using records from two hospitals. Adults with T2D and hypertension who initiated SGLT2i or GLP-1RA and had ≥2 BP readings were included. BP changes were analyzed with ANOVA; adverse events and treatment discontinuation were assessed with Chi-square and Kaplan–Meier analysis. Results: Of 505 patients, 291 (57.6%) received SGLT2i and 214 received GLP-1RA. Both classes significantly reduced SBP (p < 0.001), and DBP decreased significantly only in the SGLT2i group (p < 0.001). Antihypertensive regimen reduction occurred in 6.9% of patients, most commonly among SGLT2i users (74.3%), while 76.8% remained on the same regimen; the remaining patients had other modifications such as dosage adjustments or changes in individual agents. Adverse events occurred in 6.3% of patients with no group differences. Therapy discontinuation was higher with GLP-1RA (12.6%) versus SGLT2i (2.4%, p < 0.001). Conclusions: Both SGLT2i and GLP-1RA might be considered in patients with T2D and hypertension, with SGLT2i potentially offering additional benefits for DBP reduction and simplifying antihypertensive regimens, which could support clinical decision-making in real-world practice. Full article

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked with type 2 diabetes mellitus (T2D) and obesity. Despite its growing prevalence, effective pharmacological interventions remain limited, with antidiabetic agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) showing emerging promise. This study aimed to evaluate the impact of different antidiabetic therapies on hepatic steatosis, fibrosis, and cardiometabolic risk factors in patients with T2D and MASLD from Romania. Materials and Methods: We conducted a prospective observational study involving 256 patients with T2D and MASLD followed up for 6 months. Assessed parameters included anthropometry, glycemic indices, lipid profile, renal function, liver enzymes, and non-invasive evaluation of hepatic steatosis and fibrosis. Patients were 53% women, had a median age of 63 years, a median BMI of 32.2 kg/m², a median baseline CAP of 281 dB/m, a FibroScan of 8.9 kPa, and an HbA1c of 8.0%. Results: CAP decreased significantly from 281 to 245 dB/m, p < 0.0001; FibroScan from 8.9 to 8.0 kPa, p < 0.0001. The largest changes were observed in the GLP-1 RA subgroup (CAP −50 dB/m, FibroScan −1.0 kPa, weight −8.0 kg, HbA1c −0.7%), and in the SGLT2i subgroup (CAP −30.5 dB/m, FibroScan −0.7 kPa, weight −4.0 kg, HbA1c −0.5%). In regression analysis, independent factors associated with CAP improvement included GLP-1 RA therapy (β = 44.5, 95% CI 38.3–50.6, p < 0.0001), SGLT2i therapy (β = 23.4, 95% CI 15.7–31.1, p < 0.0001), and ≥10% weight loss (β = 23.2, 95% CI 12–34.4, p < 0.0001). For FibroScan improvement, GLP-1 RA (β = 1.0, 95% CI 0.8–1.2, p < 0.0001) and SGLT2i (β = 0.5, 95% CI 0.3–0.7, p < 0.0001) therapies were both significant. Conclusions: Antidiabetic therapy, particularly GLP-1 RA, was significantly associated with improvement in hepatic steatosis, fibrosis, and cardiometabolic risk in T2D patients with MASLD beyond the weight reduction effect. However, weight loss and lipid modulation enhance these benefits, supporting the development of integrated therapeutic strategies for this high-risk population. Full article

The aim was to assess the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RA) treatment on the progression of ascending aorta dilatation in patients with type 2 diabetes mellitus (T2DM). A total of 127 T2DM patients with subclinical ascending aortic dilatation (35–45 mm) were prospectively enrolled. Fifty-seven initiated GLP-1 RA therapy (liraglutide, semaglutide, or dulaglutide), while 70 continued on standard care. Ascending aortic diameter was measured by computed tomography angiography (CTA) at baseline and 24 months, alongside circulating markers of vascular remodeling: matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), C-reactive protein (CRP), and osteoprotegerin (OPG). Progression of aortic dilatation was significantly lower in the GLP-1 RA group compared with controls (+0.36 ± 0.20 mm vs. +1.05 ± 0.28 mm; p < 0.001). Therapy correlated with decreased MMP-9 and CRP (p < 0.01) and increased TIMP-1 and OPG (p < 0.05). The use of GLP-1 RA was an independent predictor of low progression, even in multivariate models after adjusting for demographic, metabolic, and biomarker data. GLP-1 RA therapy was associated with reduced progression of ascending aortic dilatation in T2DM, supporting a potential vasoprotective role beyond glucose lowering. Full article