Search Results (487)

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), represents a rapidly expanding global health challenge with substantial public health and economic consequences. Recent advances in antidiabetic therapy—including dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dual GIP/GLP-1 receptor agonists, and sodium–glucose cotransporter-2 (SGLT-2) inhibitors—have transformed diabetes management by providing benefits beyond glycemic control, such as cardiovascular and renal protection, weight reduction, and improved quality of life. As the therapeutic landscape becomes increasingly complex and patient-centered, ensuring the safe and effective use of these agents in real-world settings has emerged as a key concern for pharmacoepidemiology and pharmacovigilance. Community pharmacists, as highly accessible healthcare professionals, play an expanding role in diabetes care through medication optimization, patient education, adherence support, and monitoring of adverse drug reactions in primary care. Evidence from systematic reviews and meta-analyses indicates that pharmacist-led interventions improve glycemic outcomes, enhance self-care behaviors, and facilitate the appropriate adoption of contemporary antidiabetic therapies. This narrative review synthesizes current evidence on novel pharmacological treatments for T2DM and examines the evolving contribution of community pharmacists in translating therapeutic innovation into routine practice. Barriers to implementation and future perspectives for integrating pharmacist-led services into diabetes management and pharmacovigilance frameworks are also discussed. Full article

Background: Salt-sensitive blood pressure (SSBP) represents a prevalent yet underrecognized hypertensive phenotype, in which blood pressure (BP) and volume status are disproportionately influenced by dietary sodium intake. Beyond BP elevation alone, salt sensitivity reflects a convergence of renal sodium handling abnormalities, neurohormonal activation, vascular dysfunction, and inflammatory pathways that link excessive sodium exposure to progressive kidney injury and adverse cardiac remodeling. Given its association with chronic kidney disease (CKD) and the association of heart failure with preserved ejection fraction (HFpEF), improved recognition of SSBP has direct clinical relevance. Objective: This narrative review aims to synthesize current mechanistic and clinical evidence on SSBP, focusing on pathophysiology, cardiorenal interactions, diagnostic challenges, and phenotype-guided therapeutic strategies with practical applicability. Methods: A narrative literature review was conducted using PubMed, Scopus, and Web of Science from inception through January 2026. Experimental, translational, and clinical studies, along with relevant guideline documents, were integrated to provide conceptual and clinical interpretation rather than quantitative analysis. Key Findings: Impaired renal sodium excretion, intrarenal RAAS activation, sympathetic overactivity, endothelial dysfunction, and immune-mediated inflammation contribute to sodium retention, microvascular dysfunction, and fibrotic remodeling across the kidney–heart axis. These pathways are strongly supported by experimental and translational data, but direct interventional clinical validation remains limited for several mechanisms. Clinically, salt-sensitive individuals often exhibit non-dipping BP patterns, albuminuria, salt-induced edema, and a predisposition to HFpEF. Dynamic BP monitoring combined with targeted laboratory assessment improves identification of this phenotype and supports individualized management. Conclusions: Early recognition of SSBP enables targeted interventions beyond uniform sodium restriction. Phenotype-guided strategies integrating lifestyle modification, RAAS blockade, thiazide-like diuretics, mineralocorticoid receptor antagonists, and sodium-glucose co-transporters 2 inhibitors (SGLT2i) may improve cardiorenal outcomes. Emerging precision tools (e.g., wearable blood-pressure sensors, digital sodium tracking technologies, etc.) remain exploratory but may further refine individualized management. Full article

Background and Objectives: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as key agents in the management of type 2 diabetes mellitus (T2DM), with expanding indications in heart failure and chronic kidney disease. This study assessed national trends in SGLT2 inhibitor utilization in Croatia between 2014 and 2024 using data from IQVIA. Materials and Methods: Drug use was quantified in defined daily doses per 1000 inhabitants per day (DDD/1000/day), alongside financial expenditure and prescribing patterns. Results: Since their market introduction in 2014, SGLT2 inhibitor utilization increased from 0.49 to 11.63 DDD/1000/day by 2024. Fixed-dose combinations with metformin accounted for a growing share of prescribing, reflecting a shift toward adherence-friendly regimens. Dapagliflozin was the most prescribed agent, likely due to broad therapeutic versatility and favorable pricing. Despite these trends, SGLT2 inhibitors (monotherapy) seem to be underutilized, accounting for just 12% of non-insulin antidiabetic prescriptions in 2024. Conclusions: These findings highlight the gradual integration of SGLT2 inhibitors into national clinical practice and emphasize the need for targeted educational and policy efforts to overcome therapeutic inertia and align prescribing with evidence-based cardio-renal-metabolic care. Full article

Background/Objectives: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are essential antidiabetic medications. However, their side effects warrant careful consideration. The search for novel SGLT2 inhibitors with high affinity remains an ongoing endeavor. Medicine food homology (MFH) herbs show promise for drug development due to their nutritional and medicinal value. Methods: This study aims to address the shortcomings of existing virtual screening models for SGLT2 inhibitors by optimizing feature selection and integrating multidimensional molecular fingerprints. Subsequently, an integrated virtual screening pipeline is constructed to identify potential SGLT2 inhibitors from eight selected MFH herbs. Results: The results indicate that the optimal model (LightGBM and RF) achieved an accuracy of 0.97 and an AUC of 0.98. Following rigorous filtering, a total of 44 potential SGLT2 inhibitors were identified, among which, Isoononin (from Gancao) and Ononin (from Huangqi, Gegen, and Gancao) exhibit favorable drug likeness and safety. Molecular docking demonstrate that both compounds can effectively bind to the SGLT2 active site, establishing stable hydrophobic interactions with critical residues such as Phe98 and Phe453. Furthermore, molecular dynamics simulations confirm the stability of the interactions between the two compounds and SGLT2. Conclusions: This study significantly enhances the accuracy and stability of SGLT2 inhibitor virtual screening models by addressing deficiencies in structural characterization and feature selection. It provides candidate molecules for the development of novel SGLT2 inhibitors and offers new scientific evidence for the application of MFH herbs in the prevention and treatment of chronic metabolic diseases. Full article

Background/Objectives: Canagliflozin (CFZ) is the first sodium glucose co-transporter 2 (SGLT-2) inhibitor and is characterized by poor water solubility and permeability, resulting in low oral bioavailability. In this study, a CFZ nanosuspension (CFZ-NS) was converted into a solid form to improve the physical stability of CFZ nanocrystals (CFZ-NCs) and to enable formulation as a tablet dosage form. Methods: To achieve adequate redispersibility of dried CFZ-NCs, fluid bed granulation and spray-drying methods were employed, and the effects of critical process parameters were investigated. The stability of spray-dried nanocrystal tablets (NCs-SD-TAB) was evaluated over a three-month period under storage conditions of 25 ± 2 °C with 60 ± 5% relative humidity (RH) and 40 ± 2 °C with 75 ± 5% RH. Results: The highest redispersibility index (94%) was obtained using the spray-drying method. Tablets prepared with spray-dried NCs-SD-TAB exhibited a significantly higher in vitro dissolution rate under non-sink conditions compared with control tablets prepared using unprocessed CFZ with the same excipients, as well as the marketed product. NCs-SD-TAB showed an approximately three-fold increase in drug release at 15 min in 0.1 N HCl, with a pH 4.5 acetate buffer and pH 6.8 phosphate buffer, which simulate gastrointestinal pH conditions, relative to the marketed product. Conclusions: Overall, these results indicate that nanocrystal technology represents a promising approach for CFZ as an improved oral drug-delivery system, primarily due to its solubility enhancement capabilities. Full article

Background/Objectives: Sodium-glucose cotransporter 2 (SGLT2) inhibitors provide well-established cardiovascular and renal benefits in heart failure (HF), type 2 diabetes (T2DM), and chronic kidney disease (CKD). Although emerging trials suggest potential value after acute myocardial infarction (AMI), SGLT2 inhibitors currently have no formal indication for AMI, and real-world prescribing patterns in this setting remain uncharacterized. This study aimed to evaluate in-hospital and post-discharge prescribing patterns and clinical predictors of SGLT2 inhibitor initiation among AMI patients eligible for therapy based on guideline-supported indications. Methods: We conducted a retrospective cohort study including 244 consecutive AMI patients hospitalized between January 2023 and July 2024. A total of 180 (73.7%) met guideline-based eligibility criteria for SGLT2 inhibitors. Four multivariable logistic regression models were developed to identify independent predictors of SGLT2 inhibitor prescription. Results: A total of 117 patients (65%) received SGLT2 inhibitors and 63 (35%) remained untreated. Receivers were more frequently male (81% vs. 65%) and exhibited lower left ventricular ejection fraction (LVEF) (38.2 ± 6.7% vs. 42.4 ± 8.3%), larger ventricular volumes, and higher Killip class at presentation. HF patients with preserved ejection fraction (HFpEF) were markedly undertreated (25.9%) compared with mid-range (HFmrEF) (69.8%) or reduced (HFrEF) (73.7%). Across all models, HFpEF was a strong negative predictor of prescribing (OR 0.071–0.081, p < 0.001), while male sex and markers of clinical severity were associated with higher likelihood of initiation. Many untreated patients had T2DM or CKD despite guideline-based eligibility. No serious adverse events attributable to SGLT2 inhibitors were reported. Conclusions: In this real-world AMI cohort, SGLT2 inhibitors were prescribed primarily in relation to established indications for HF, T2DM, and CKD, yet their use remained highly variable in the absence of a dedicated recommendation for AMI. Significant therapeutic gaps were observed in HFpEF and high-risk cardiometabolic profiles, underscoring the need for clearer guidance and standardized pathways to support consistent initiation in eligible patients after MI. Full article

Background and Objectives: Heart failure frequently coexists with CKD, compounding prognosis via cardio-renal interplay. Sodium glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular and renal benefits in randomized trials, but data remain limited in real-world lower-resource settings. Materials and Methods: We conducted a retrospective single-center cohort study at a tertiary university hospital in western Romania, including adults with chronic HF and LVEF ≤ 45%, monitored between 2021–2024. Patients were stratified based on receipt of SGLT2 inhibitors. The primary endpoint was a composite of cardiovascular death, HF hospitalization, or ≥40% sustained decline in eGFR/initiation of KRT. Annual eGFR slope was analyzed to assess renal trajectory. Results: Among 240 patients, treatment with SGLT2 inhibitors was associated with a lower risk of the composite cardio-vasculo-renal endpoint compared with no treatment (adjusted HR 0.70, 95% CI 0.50–0.98). The reduction was primarily driven by fewer heart failure hospitalizations. Decline in kidney function was slower among SGLT2 inhibitor-treated patients in longitudinal mixed-effects analyses. Conclusions: In this retrospective cohort, SGLT2 inhibitor use was associated with fewer cardio-renal events and a slower decline in kidney function. Given the observational design and residual confounding risk, these findings should be considered hypothesis-generating but provide implementation-relevant signals supporting further prospective evaluation. Full article

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) coexist in 40–60% of cases and mutually reinforce each other through adverse electrical, cellular, and functional remodelling. There is considerable overlap in signs and symptoms, and diagnosis may be challenging due to nonspecific clinical presentations and chronic course. AF is clearly linked with worsening morbidity and mortality in HFpEF with higher rates of HF hospitalizations, HF progression, stroke, systemic embolism, and all-cause death. Optimal management of HFpEF-AF patients requires aggressive treatment of comorbidities and risk factor modification. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated consistent benefit with respect to HF hospitalizations, symptoms and exercise haemodynamics, and potential to reduce AF burden. Gastric inhibitory polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) agonists, mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and statins may provide benefit in selected phenotypes, though evidence remains heterogeneous. A rhythm control strategy in the early clinical course of HFpEF might be a reasonable strategy to improve symptoms and delay both AF and HFpEF disease progression. Catheter ablation appears to improve exercise haemodynamics and quality of life, and observational data suggest it may reduce mortality and HF hospitalization, though current evidence is inconsistent and not yet definitive. Emerging device-based and molecular therapies could represent promising avenues for future research. Overall, early detection of AF, comprehensive risk-factor modification, and tailored rhythm-control strategies are central to improving outcomes in the HFpEF-AF overlap syndrome. Full article

Background: Alzheimer’s disease (AD) features progressive cognitive decline and amyloid-beta (Aβ) accumulation. Insulin resistance in type 2 diabetes mellitus (T2DM) is increasingly recognised as a mechanistic link between metabolic dysfunction and neurodegeneration. Although sodium–glucose cotransporter-2 inhibitors (SGLT2is) have established glycaemic and cardioprotective benefits, their neuroprotective role remains less well defined. Objectives: This systematic review examines animal studies on the neuroprotective effects of SGLT2i in T2DM and AD models. Methods: A literature search was conducted across the Web of Science, Scopus, and PubMed databases, covering January 2014 to November 2024. Heterogeneity was assessed with I², and data were pooled using fixed-effects models, reported as standardised mean differences with 95% confidence intervals. We focus on spatial memory performance as measured by the Morris Water Maze (MWM) test, including escape latency and time spent in the target quadrant, as the primary endpoints. The secondary endpoints of Aβ accumulation, oxidative stress, and inflammatory markers were also analysed and summarised. Results: Twelve studies met the inclusion criteria for this review. A meta-analysis showed that SGLT2i treatment significantly improved spatial memory by reducing the escape latency in both T2DM and AD models. In addition, SGLT2i yielded a significant improvement in spatial memory, as indicated by an increased target quadrant time for both T2DM and AD. Furthermore, SGLT2i reduced Aβ accumulation in the hippocampus and cortex, which met the secondary endpoint; the treatment also lessened oxidative stress and inflammatory markers in animal brains. Conclusions: Our findings indicate that SGLT2is confer consistent neuroprotective benefits in experimental T2DM and AD models. Full article

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors), initially developed for glycemic control in type 2 diabetes, have demonstrated robust cardiovascular and renal benefits. Emerging evidence suggests that these agents may also affect valvular pathobiology, particularly in degenerative aortic stenosis (AS), through anti-inflammatory and antifibrotic mechanisms. Objectives: This study evaluated whether SGLT2 inhibitor use is associated with improved clinical outcomes in degenerative AS, including all-cause mortality and the need for SAVR or TAVR, recognizing that these endpoints represent surrogate rather than direct measures of valve hemodynamic progression. Methods: A retrospective cohort analysis was conducted using TriNetX, a federated electronic medical record-based research network. Diagnoses are captured using ICD-9/ICD-10-CM codes and medications using ATC codes. Adults with non-rheumatic AS were stratified by SGLT2 inhibitors use. Propensity score matching (1:1) was performed to balance baseline characteristics between treated and untreated groups (n = 10,912 per group). Primary outcomes included all-cause mortality, TAVR, and SAVR during follow-up. Echocardiographic parameters (AVA, Vmax, mean gradient) were not systematically available. Results: After adjustment for comorbidities, SGLT2 inhibitor use was independently associated with lower all-cause mortality (6.15% vs. 9.34% HR 0.595; 95% CI 0.552–0.641; p < 0.001), TAVR (2.81% vs. 2.89% HR 0.835; 95% CI 0.746–0.934; p = 0.002), SAVR (1.28% vs. 1.90% HR 0.514; 95% CI 0.442–0.599; p < 0.001), cardiac arrest (0.82% vs. 1.21% HR 0.71; 95% CI 0.582–0.867; p < 0.001), and end-stage kidney disease (0.40% vs. 1.0% HR 0.292; 95% CI 0.222–0.384; p < 0.001). Although these associations may suggest slower disease progression, interpretation is limited by the lack of systematic echocardiographic follow-up. Conclusions: In addition to their established benefits in heart failure and renal protection, SGLT2 inhibitors may have valve-preserving effects in degenerative AS. Because true hemodynamic progression could not be evaluated, these results should be viewed as associations with surrogate clinical endpoints. Prospective studies with standardized imaging are required to determine whether SGLT2 inhibition can directly alter the course of this currently untreatable disease Full article

Background: Systemic inflammation plays a central role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Hematologic inflammatory indices-such as the Systemic Immune-Inflammation Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR)-have emerged as accessible markers of chronic inflammation, yet longitudinal comparisons across oral antidiabetic therapies remain limited. This study uniquely integrates longitudinal correlation and network analyses in a large real-world T2DM cohort, allowing assessment of the temporal stability and class-specific inflammatory patterns across four oral antidiabetic therapies. Methods: This retrospective, longitudinal study analyzed 13,425 patients with T2DM treated with Biguanidines, Dipeptidyl Peptidase-4 (DPP-4) inhibitors, Sodium–Glucose Cotransporter-2 (SGLT-2) inhibitors or Thiazolidinediones (TZDs) between 2020 and 2024. Data were retrieved from the Probel^® Hospital Information System and included baseline, early (30–180 days), and late (180–360 days) follow-up laboratory results. Systemic inflammatory indices were computed from hematologic parameters, and correlations among inflammatory and biochemical markers were assessed using Spearman’s coefficients. Results: At baseline, all hematologic indices were strongly intercorrelated (SII–NLR r = 0.83, p < 0.001; SII–PLR r = 0.73, p < 0.001), with moderate associations to C-reactive protein (CRP; r ≈ 0.3–0.4) and weak or no correlations with Ferritin (r ≈ −0.1). These relationships remained stable throughout follow-up, confirming reproducibility of systemic inflammatory coupling. Longitudinally, SII and NLR showed modest early increases followed by significant declines at one year (p < 0.05), while PLR and MLR remained stable. Class-specific differences were observed: SGLT-2 inhibitors and TZDs demonstrated stronger and more integrated anti-inflammatory networks, whereas Biguanidines and DPP-4 inhibitors exhibited moderate coherence. Principal Component Analysis (PCA) explained 62.4% of total variance and revealed distinct clustering for TZD and SGLT-2 groups, reflecting class-specific inflammatory modulation. Conclusions: Systemic inflammatory indices (SII, NLR, PLR) provide reproducible and accessible measures of low-grade inflammation in T2DM. Despite overall inflammation reduction with treatment, drug-specific patterns emerged-SGLT-2 inhibitors and TZDs showed greater anti-inflammatory coherence, while Biguanidines and DPP-4 inhibitors maintained moderate effects. Full article

Type 2 diabetes mellitus (T2DM) involves chronic hyperglycemia, insulin resistance, low-grade inflammation, and oxidative stress that drive cardiometabolic and renal damage despite current therapies. Sodium–glucose cotransporter (SGLT) inhibitors have reshaped the treatment landscape, but residual risk and safety concerns highlight the need for new agents that combine glucose-lowering efficacy with redox–inflammatory modulation. LASSBio-1986 is a synthetic N-acylhydrazone (NAH) derivative designed as a gliflozin-like scaffold with the potential to interact with SGLT1/2 while also influencing oxidative and inflammatory pathways. Here, we integrated in silico and in vivo approaches to characterize LASSBio-1986 as a multifunctional antidiabetic lead in murine models of glucose dysregulation. PASS and target class prediction suggested a broad activity spectrum and highlighted transporter- and stress-related pathways. Molecular docking indicated high-affinity binding to both SGLT1 and SGLT2, with a modest energetic preference for SGLT2, and ADME/Tox predictions supported favorable oral drug-likeness. In vivo, intraperitoneal LASSBio-1986 improved oral glucose tolerance and reduced glycemic excursions in an acute glucose challenge model in C57BL/6 mice, while enhancing hepatic and skeletal muscle glycogen stores. In a dexamethasone-induced insulin-resistance model, LASSBio-1986 improved insulin sensitivity, favorably modulated serum lipids, attenuated thiobarbituric acid-reactive substances (TBARS), restored reduced glutathione (GSH) levels, and rebalanced pro- and anti-inflammatory cytokines in metabolic tissues, with efficacy broadly comparable to dapagliflozin. These convergent findings support LASSBio-1986 as a preclinical, multimodal lead that targets SGLT-dependent glucose handling while mitigating oxidative and inflammatory stress in models relevant to T2DM. Chronic disease models, formal toxicology, and pharmacokinetic studies, particularly with oral dosing, will be essential to define its translational potential. Full article

Berberine (BBR), a protoberberine alkaloid with a long history of medicinal use, has consistently demonstrated benefits in glucose–lipid metabolism and inflammatory balance across both preclinical and human studies. These diverse effects are not mediated by a single molecular target but by BBR’s capacity to restore network coordination among metabolic, immune, and microbial systems. At the core of this regulation is an AMP-activated Protein Kinase (AMPK)-centered mechanistic hub, integrating signals from insulin and nutrient sensing, Sirtuin 1/3 (SIRT1/3)-mediated mitochondrial adaptation, and inflammatory pathways such as nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-κB) and NOD-, LRR- and Pyrin Domain-containing Protein 3 (NLRP3). This hub is dynamically regulated by system-level inputs from the gut, mitochondria, and epigenome, which in turn strengthen intestinal barrier function, reshape microbial and bile-acid metabolites, improve redox balance, and potentially reverse the epigenetic imprint of metabolic stress. These interactions propagate through multi-organ axes, linking the gut, liver, adipose, and vascular systems, thus aligning local metabolic adjustments with systemic homeostasis. Within this framework, BBR functions as a negentropic modulator, reducing metabolic entropy by fostering a coordinated balance among these interconnected systems, thereby restoring physiological order. Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub–axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling. Full article

Canagliflozin (CFZ), a sodium–glucose cotransporter 2 (SGLT2) inhibitor, is extensively utilized in the management of type 2 diabetes. Among its various polymorphic forms, the hemi-hydrate (Hemi-CFZ) has been selected as the active pharmaceutical ingredient (API) for CFZ tablets due to its superior solubility. However, during the production, storage, and transportation of CFZ tablets, Hemi-CFZ can undergo transformations into anhydrous (An-CFZ) and monohydrate (Mono-CFZ) forms under the influence of environmental factors such as temperature, humidity, and pressure, which may adversely impact the bioavailability and clinical efficacy of CFZ tablets. Therefore, it is imperative to develop rapid, accurate, non-destructive, and non-contact methods for quantifying An-CFZ and Mono-CFZ content in CFZ tablets to control polymorphic impurity levels and ensure product quality. This research evaluated the feasibility and reliability of using near-infrared spectroscopy (NIR) combined with partial least squares regression (PLSR) for simultaneous quantitative analysis of An-CFZ and Mono-CFZ in CFZ tablets, elucidating the quantifying mechanisms of the quantitative analysis model. Orthogonal experiments were designed to investigate the effects of different pretreatment methods and ant colony optimization (ACO) algorithms on the performance of quantitative models. An optimal PLSR model for simultaneous quantification of An-CFZ and Mono-CFZ in CFZ tablets was established and validated over a concentration range of 0.0000 to 10.0000 w/w%. The resulting model, Y_{An-CFZ/Mono-CFZ} = 0.0207 + 0.9919 X, achieved an R² value of 0.9919. By analyzing the relationship between the NIR spectral signals selected by the ACO algorithm and the molecular structure information of An-CFZ and Mono-CFZ, we demonstrated the feasibility and reliability of the NIR-PLSR approach for quantifying these polymorphic forms. Additionally, the mechanism of PLSR quantitative analysis was further explained through the variance contribution rates of latent variables (LVs), the correlations between LVs loadings and tablets composition, and the relationships between LV scores and An-CFZ/Mono-CFZ content. This study not only provides a robust method and theoretical foundation for monitoring An-CFZ and Mono-CFZ content in CFZ tablets throughout production, processing, storage, and transportation, but also offers a reliable methodological reference for the simultaneous quantitative analysis and quality control of multiple polymorphic impurities in other similar drugs. Full article

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel obstruction, clarifying agent- and dose-specific gastrointestinal safety is clinically important. We aimed to re-evaluate the risk of intestinal obstruction across individual GLP-1 receptor agonists and SGLT2 inhibitors, with particular attention to dose stratification. We systematically searched eight databases through 21 January 2025 to identify randomized controlled trials (RCTs) comparing GLP-1 receptor agonists or SGLT2 inhibitors with placebo or active comparators in adults. The primary outcome was incident intestinal obstruction (small or large bowel). A frequentist random-effects network meta-analysis estimated odds ratios (ORs) with 95% confidence intervals (CIs) across drugs and dose tiers; Bayesian models and surface under the cumulative ranking (SUCRA) metrics were used for sensitivity analyses and treatment ranking. Risk of bias and certainty of evidence were assessed with standard Cochrane and GRADE-adapted tools. Fifty RCTs (47 publications; 192,359 participants) met inclusion criteria. Overall, canagliflozin use was associated with a higher incidence of intestinal obstruction than control therapies (OR 2.56, 95% CI 1.01–6.49), corresponding to an absolute risk difference of 0.15% and a number needed to harm of 658. High-dose canagliflozin (300 mg/day) showed the clearest signal (OR 3.42, 95% CI 1.08–10.76). In contrast, liraglutide was associated with a lower risk of intestinal obstruction (OR 0.44, 95% CI 0.24–0.81), with an absolute risk reduction of 0.34% and a number needed to treat of 295. No other GLP-1 receptor agonist or SGLT2 inhibitor demonstrated a statistically significant increase in obstruction risk. Frequentist and Bayesian analyses yielded concordant estimates and rankings. From a randomized-trial perspective, intestinal obstruction risk is not elevated for most GLP-1 receptor agonists and SGLT2 inhibitors. A dose-dependent safety signal was observed only for high-dose canagliflozin, whereas liraglutide may confer a protective effect. These findings refine gastrointestinal safety profiles for modern antidiabetic agents and may inform perioperative bowel management, drug selection, and dose optimization in patients at risk for ileus or adhesive obstruction. Full article