Search Results (78)

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

Introduction: Overweight and obesity are becoming increasingly prevalent. Incretin-based obesity treatments—glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor agonists (GIP/GLP-1 RAs or dual agonists)—are a major stride in the evolution of obesity management. However, like weight loss with other means, they are associated with an inadvertent significant loss of lean body mass, including muscle. This has led to a resurgence in research for the preservation of lean body mass, the loss of which occurs with weight loss. The purpose of this narrative review is to discuss the mechanisms involved with lean body loss and capture the research landscape of the different classes of pharmacological agents being developed to address this problem. Methodology: We queried PubMed, Medline, and Scopus for randomized controlled trials and phase II or phase III trials using key words to capture the breath of this topic—obesity, weight loss, muscle loss, lean mass, and muscle preservation. Animal studies were excluded. We analyzed the studies conducted to date. Results: Weight loss, regardless of the method used to achieve it, is inadvertently accompanied by lean body mass loss, to varying degrees. There are several mechanisms that govern the loss of lean body mass and, more specifically, the loss of muscle mass; as such, several classes of medications have been explored, targeting different pathways and receptors—including bimagrumab (activin receptor agonist), tesamorelin (growth hormone releasing hormone agonists), and enobosarm (selective androgen receptor modulator). Most of these drugs are in the early phases of research development, but some show great promise. Conclusion: This narrative review attempts to detail the physiology of muscle mass loss when accompanied by weight loss and identify pharmacological targets that can be utilized to minimize it with mechanisms, effects, side effects, and research developmental progress. Full article

Background: Alcohol use disorder (AUD) is associated with chronic heavy or repeated binge alcohol abuse, which can cause alcohol-related brain damage (ARBD) marked by neurobehavioral, cognitive, and motor deficits. The anterior frontal lobe and cerebellar vermis are two of the major targets of ARBD in humans with AUD and in experimental alcohol exposed models. Alcohol’s neurotoxic and neurodegenerative effects include impairments in signaling through insulin and insulin-like growth factor (IGF) pathways that regulate energy metabolism. This human AUD study was inspired by a recent report suggesting that dysfunction of the frontal lobe incretin network in experimental ARBD is linked to known impairments in brain insulin/IGF signaling. Objective: The overarching goal was to investigate whether AUD is associated with dysfunction of the brain’s incretin network, focusing on the cerebellum and frontal lobe. Methods: Fresh frozen postmortem cerebellar vermis and anterior frontal lobe tissues from adult male AUD (n = 6) and control (n = 6) donors were processed for protein extraction. Duplex enzyme-linked immunosorbent assays (ELISAs) were used to assess immunoreactivity to neurofilament light chain (NfL) as a marker of neurodegeneration. A multiplex ELISA was used to measure immunoreactivity to a panel of gut hormones, including incretin polypeptides. Results: AUD was associated with significantly increased NfL immunoreactivity in both the cerebellar vermis and anterior frontal lobe. However, the patterns of AUD-related alterations in gut hormone immunoreactivity differed regionally. AUD reduced pancreatic polypeptide immunoreactivity in the cerebellar vermis, and GIP, GLP-1, leptin, and ghrelin in the frontal lobe. Conclusions: (1) Increased NfL may serve as a useful biomarker of neurodegeneration in AUD. (2) AUD’s adverse effects on neuroendocrine signaling networks differ in the cerebellar vermis and anterior frontal region, although both are significant targets of ARBD. (3) The finding of AUD-associated reductions in frontal lobe GIP and GLP-1 suggests that therapeutic targeting with incretin receptor agonists may help restore energy metabolism and neurobehavioral and cognitive functions linked to their networks. Full article

Background: Obesity management is evolving with the integration of dual GIP/GLP-1 receptor agonists (Tirzepatide) into comprehensive Digital Weight-Loss Services (DWLSs). This model leverages virtual, app-based multidisciplinary care (MDT) to deliver continuous, supervised treatment, distinguishing it from traditional, intermittent clinic-based care. While clinical trials demonstrate high efficacy, real-world data are necessary to evaluate long-term adherence and identify predictive markers for patient persistence in these scalable care models. Specifically, there is a knowledge gap regarding the specific behavioral factors that govern 12-month persistence in these comprehensive, medicated DWLS settings. This study retrospectively assessed the 12-month effectiveness and adherence of a Tirzepatide-supported DWLS and identified demographic, clinical, and behavioral predictors of weight loss and program attrition. Methods: Data from 19,693 patients enrolled in the Juniper UK DWLS were analyzed. Adherence was defined by a minimum of 10 medication orders and 12-month weight submission. Weight loss in the full cohort was evaluated using the Last Observation Carried Forward (LOCF) method. Binary logistic and multiple linear regression models identified predictors of adherence and weight loss, respectively, using a comprehensive set of demographic, clinical (e.g., BMI, comorbidities), and behavioral variables. Results: The 12-month adherence rate was 27%. The adherent sub-cohort (n = 5322) achieved a mean weight loss of 22.60 (±7.46) percent, compared to 13.62 (±10.85) percent in the full cohort (LOCF). This difference in 12-month mean weight loss was statistically significant (p < 0.001). Consistent weekly weight tracking and health coach communication were the strongest positive predictors of long-term adherence and weight loss. Conversely, hyper-engagement, specifically intensive tracking frequency and high weight loss velocity in the first month, was a significant inverse predictor of 12-month adherence. Reporting side effects was positively correlated with adherence, suggesting a reporting bias among engaged patients. Conclusions: The DWLS model facilitates the maximum therapeutic effectiveness for adherent patients. However, patient persistence remains the primary translational challenge. As consistent weekly engagement (tracking, coaching) is the strongest predictor of success, clinical strategies should prioritize promoting sustainable, moderate behavioral pacing (i.e., emphasizing consistent weekly engagement over intensive daily tracking and rapid early weight loss) to mitigate attrition risk and optimize the public health effectiveness of medicated DWLSs. Full article

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) play central roles in metabolic and cardiovascular regulation. GLP-1 receptor agonists (GLP-1RAs) are established therapies for type 2 diabetes mellitus (T2DM) and obesity because of their insulinotropic effects, weight reduction, and proven cardiovascular benefit in trial level. In contrast, GIP was historically overlooked due to reduced β-cell responsiveness in T2DM. The development of dual GIP/GLP-1 receptor agonists has reshaped this view. Tirzepatide, the first-in-class co-agonist, an antidiabetic medication to treat type 2 diabetes and for weight loss, provides superior glycemic control and weight loss compared with selective GLP-1RAs in clinical trials, demonstrating synergistic actions between the two incretin pathways. This review summarizes key physiology, pathophysiology, and therapeutic evidence in incretin biology. We describe secretion patterns, receptor distributions, and distinct actions of GIP and GLP-1, as well as alterations in incretin signaling in T2DM and obesity. Cardiovascular protective mechanisms are outlined, including improvements in lipid metabolism, reductions in blood pressure, enhanced endothelial nitric oxide activity, suppression of macrophage inflammation, decreased foam-cell formation, and stabilization of atherosclerotic plaques. At the therapeutic level, emerging directions—such as dual and triple agonists—and unresolved questions regarding long-term vascular effects of GIP and the potential for genotype-guided incretin therapy are also discussed. Collectively, these findings highlight an emerging shift toward integrated incretin-axis modulation as a therapeutic strategy for metabolic and cardiovascular disease. Full article

Background: Abdominal wall hernias represent a significant global surgical burden, with over 20 million repairs performed annually. The convergence of rising obesity and diabetes rates with complex hernia management has necessitated innovative preoperative optimization strategies that address both metabolic dysfunction and mechanical challenges. Objectives: This comprehensive review synthesizes current evidence on emerging pharmacologic and procedural optimization strategies for patients undergoing abdominal wall hernia repair, with particular emphasis on glucagon-like peptide-1 (GLP-1) receptor agonists, botulinum toxin A (BTA) injections, progressive preoperative pneumoperitoneum (PPP) and biomechanical calculated repair. Methods: We conducted an extensive literature review incorporating recent clinical trials, observational studies, and meta-analyses, focusing on metabolic optimization with GLP-1 receptor agonists, mechanical preparation techniques, and their comparative effectiveness in reducing perioperative complications and hernia recurrence. Results: GLP-1 and GLP-1/GIP agonists demonstrate substantial metabolic benefits including weight reduction (10–20%), improved glycemic control, reduced systemic inflammation, and decreased postoperative complications in surgical populations. Recent evidence suggests reduced surgical site infection, thromboembolic events, and wound dehiscence in GLP-1 receptor agonists users. However, concerns regarding delayed gastric emptying and aspiration risk require careful perioperative management. BTA and PPP remain valuable techniques for mechanical optimization in loss-of-domain hernias, though modern biomechanically calculated repair (BCR) approaches using cyclic load analysis may reduce their necessity in many cases. The GRIP/CRIP concept demonstrates superior outcomes with 5–7% five-year recurrence rates compared to 15% with conventional approaches. Emerging evidence highlights collagen metabolism dysfunction as a fundamental determinant of hernia recurrence, prompting development of collagen-focused prehabilitation programs incorporating nutritional supplementation, aquatic exercise, and targeted physical conditioning. Conclusions: A paradigm shift toward integrated, personalized preoperative optimization is emerging, combining metabolic conditioning with mechanical preparation based on individual patient phenotypes and hernia complexity. Future research should focus on comparative effectiveness trials, optimal timing protocols, and multimodal strategies to maximize surgical outcomes while minimizing complications. Full article

Background: Patients with type 2 diabetes mellitus (T2DM) and inflammatory bowel disease (IBD) face elevated risk of hepatobiliary complications. The biliary safety of GLP-1 and dual GLP-1/GIP receptor agonists in this population is uncertain. Methods: We conducted a retrospective cohort study using the TrinetX LIVE global health research network. Adults (≥18 years) with coexisting T2DM and IBD were assigned to exposure (semaglutide or tirzepatide) or comparator (no GLP-1/GIP therapy) cohorts. The index was first prescription (or matched date). Primary outcomes—cholelithiasis, cholecystitis, choledocholithiasis, and cholangitis—were identified by ICD-10 codes. Propensity score matching (1:1 greedy nearest neighbor; caliper 0.1 SD) balanced demographics, comorbidities, GI surgeries, and antidiabetic medications. Results: After propensity score matching, 32,052 patients were included (16,026 per cohort), achieving excellent covariate balance with standardized mean differences < 0.1 for nearly all variables. GLP-1/GIP agonist use was associated with significantly lower risks of multiple biliary complications. Cholelithiasis occurred in 3.5% of GLP-1/GIP users compared with 6.3% of nonusers (risk ratio [RR] 1.81, 95% CI 1.64–2.00; hazard ratio [HR] 1.27, 95% CI 1.14–1.41; p < 0.001). Cholecystitis similarly occurred less frequently among users (0.8% vs. 2.2%; RR 2.74, 95% CI 2.24–3.34; HR 1.85, 95% CI 1.50–2.27; p < 0.001). Choledocholithiasis was also reduced in the GLP-1/GIP cohort (0.6% vs. 1.5%; RR 2.72, 95% CI 2.14–3.46; HR 1.90, 95% CI 1.48–2.44; p < 0.001). Cholangitis events were rare in both groups (0.1% vs. 0.2%) with no significant difference on survival analysis (HR 1.07, 95% CI 0.58–1.97; p = 0.08). Conclusions: In adults with T2DM and IBD, GLP-1 and dual GLP-1/GIP receptor agonists are associated with substantially reduced risks of gallstone-related complications. These real-world data support the gastrointestinal safety of GLP-1–based therapy in a high-risk population and suggest possible biliary protective effects warranting prospective, agent-specific studies. Full article

Background and Objectives: GLP-1 receptor agonists (GLP-1 RAs; ATC A10BJ) and dual GLP-1/GIP agonist (ATC A10BX16) have expanded rapidly due to strong evidence in type 2 diabetes, obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Their high acquisition costs and accelerating uptake make them key drivers of pharmaceutical expenditure. This study quantified national utilization and expenditure trends for antihyperglycemic drugs in Croatia (2017–2024), with a focus on GLP-1 RA and dual GLP-1/GIP agonists. Materials and Methods: Aggregate national data on dispensed medicines, valued at wholesale pharmacy prices, were obtained from HALMED’s annual ATC/DDD reports. Utilization was expressed as defined daily doses per 1000 inhabitants per day (DDD/1000/day). We analyzed the total A10 and key subclasses. The dual GLP-1/GIP agonist was only marketed in 2024. Compound annual growth rates (CAGR) were calculated. Results: The total antihyperglycemic utilization increased from 66.9 to 96.8 DDD/1000/day (a 44.7% rise), while the total A10 expenditure increased from EUR 54.2 million to EUR 96.5 million, indicating that expenditure growth outpaced utilization growth. GLP-1 receptor agonist expenditure increased from EUR 5.2 million (2018) to EUR 28.6 million (2024) (CAGR 33.0%), reaching 29.8% of total A10 expenditure in 2024. Expenditure for GLP-1-based agents grew faster than their DDD volume because per-DDD acquisition costs are substantially higher than for SGLT-2 inhibitors. These growth patterns are consistent with trajectories reported in higher-uptake EU health systems, suggesting convergence rather than an outlier position for Croatia. Conclusions: Croatia experienced a rapid shift towards GLP-1 RA-based antihyperglycemic pharmacotherapy, with GLP-1-based therapies exerting a disproportionate budget impact. For payers, these surveillance data support budget forecasting and negotiation of pricing and reimbursement conditions; clinicians can use them to benchmark and optimize evidence-aligned prescribing; and policymakers can apply them to monitor the diffusion and fiscal impact of high-cost therapies. Routine national ATC/DDD analysis, complemented by HZZO claims and primary-care datasets, is essential for guiding future pricing, reimbursement and formulary decisions. Full article

Background/Objectives: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have revolutionised obesity and type 2 diabetes management through effective weight loss and metabolic regulation. However, their increasing use has led to reports of adverse aesthetic and functional effects, particularly affecting facial and ocular tissues. Methods: A comprehensive literature review was conducted in October 2025 across PubMed, Embase, and Medline using the terms “GLP-1 receptor agonist,” “Ozempic face,” “facial lipoatrophy,” “ocular surface disease,” “orbital fat,” and related combinations. Studies reporting facial, periorbital, orbital, or ocular surface changes associated with GLP-1 or GLP-1/GIP receptor agonists were included. Reference lists were screened to identify additional sources. Results: Evidence suggests that GLP-1 and dual GLP-1/GIP receptor agonists may contribute to rapid facial volume loss, dermal fat atrophy, and periocular hollowing—collectively termed “Ozempic face.” The mechanism is multifactorial, involving both weight-loss-related fat depletion and potential modulation of adipocyte differentiation. Ocular surface improvements have been observed in some studies. Radiologic data demonstrate preferential superficial midface fat loss, informing potential aesthetic correction strategies. Conclusions: GLP-1-based therapies, while clinically effective, can result in perceptible adnexal and periocular changes with aesthetic and functional implications. Awareness of these effects is crucial for multidisciplinary management. Future prospective studies are warranted to clarify mechanisms and guide individualised reconstructive and rejuvenative interventions. Full article

Alcohol’s chronic neurotoxic and degenerative effects mediate alcohol-related brain damage (ARBD), which is marked by neurobehavioral, cognitive, and motor deficits. Major underlying abnormalities include impairments in signaling through the insulin and insulin-like growth factor (IGF) pathways, which regulate energy metabolism. This study examined the potential role of dysregulated incretin network-related mechanisms as mediators of ARBD and evaluated a non-invasive serum exosome (S-EV)-based approach for detecting brain abnormalities. Frontal lobe tissue and S-EVs isolated from Long–Evans adolescent rats maintained for 2 weeks on control or 24% ethanol (caloric) containing liquid diets (n = 8/group) were analyzed using multiplex magnetic bead-based enzyme-linked immunosorbent assays (ELISAs). ARBD was associated with significantly reduced insulin, C-peptide, glucagon, ghrelin, leptin, GIP, and amylin levels in the frontal lobe and/or S-EV samples. In contrast, chronic ethanol exposure had no significant effects on PP, PYY, or GLP-1, and it did not increase proinflammatory cytokine expression. Chronic ethanol feeding broadly affected (primarily inhibiting) the expression of metabolic hormones linked to insulin/IGF signaling. The reductions in GIP and amylin suggest potential targets for therapeutic intervention to enhance brain energy metabolism via insulin networks. On the other hand, the findings suggest that GLP-1 receptor agonists may have limited efficacy in remediating the effects of ARBD. Finally, the results support the use of non-invasive S-EV assays to detect and guide treatment for metabolic brain dysfunction in ARBD. Full article

Background: Obesity confers substantial cardiometabolic risk. Tirzepatide, a once-weekly dual GIP/GLP-1 receptor agonist, produces dose-dependent weight loss in trials, but real-world patient-reported experiences are under-described. We evaluated real-world self-efficacy and experiences with tirzepatide in community settings. Methods: Explanatory sequential mixed-methods study of adults aged 18–59 years using tirzepatide for weight management. We collected a quantitative survey (demographics; medication use; 20-item Weight Efficacy Lifestyle Questionnaire [WEL]) followed by purposive semi-structured interviews. Associations between WEL and participant characteristics were tested a priori (two-tailed α = 0.05). Results: Among 120 participants (50.8% male; mean age 42 ± 13 years), 91.7% reported weight loss and 85.8% had <6 months’ exposure. WEL total was 91 ± 34. Higher WEL was observed in females, employed participants, those with insurance coverage versus self-pay, during early months of therapy, and among those with prior weight-loss attempts (all p < 0.05). Interviews (n = 15) indicated high satisfaction, improved sleep/energy, mood, and confidence; gastrointestinal effects were usually mild/transient. Interpretation: In routine care, tirzepatide use was associated with high eating self-efficacy and positive patient-reported outcomes. Variation by coverage and duration suggests value in pairing pharmacotherapy with behavioral support and addressing affordability to sustain benefits. Full article

Therapeutic innovation in cardiovascular medicine is rapidly overcoming the limitations of conventional strategies, providing more targeted, durable, and multidimensional solutions. Key advances include next-generation lipid-lowering agents such as PCSK9 inhibitors, inclisiran, and bempedoic acid, as well as metabolic drugs like SGLT2 inhibitors, GLP-1 receptor agonists, and dual GIP/GLP-1 agonists, which offer cardiovascular and renal benefits beyond glucose control. At the same time, gene therapies, RNA-based interventions, genome editing tools, and nanocarriers are paving the way for precision medicine tailored to individual patient profiles. In parallel, digital innovations, including artificial intelligence, remote monitoring, and telehealth platforms, are transforming care delivery by enhancing adherence, enabling earlier intervention, and refining risk stratification. Collectively, these developments signify a paradigm shift toward a more personalized, proactive, and systems-based model of cardiovascular care. Full article

Lipedema is a chronic, progressive adipose tissue disorder that affects up to 10% of women and is characterized by disproportionate lower-limb fat accumulation, pain, edema, and resistance to conventional weight-loss approaches. Its pathophysiology involves a complex interplay of adipocyte hypertrophy, chronic inflammation, extracellular matrix fibrosis, mitochondrial dysfunction, and sex steroid imbalance, highlighting the need for disease-modifying therapies. This narrative review synthesizes mechanistic, translational, and clinical evidence linking metabolic, inflammatory, and fibrotic pathways to lipedema and tirzepatide’s potential therapeutic relevance. Tirzepatide, a dual GLP-1 (Glucagon-Like Peptide-1)/GIP (Glucose-Dependent Insulinotropic Polypeptide) receptor agonist, has demonstrated unprecedented efficacy in obesity and diabetes, alongside pleiotropic actions on inflammation, fibrosis, and adipose remodeling. Mechanistic studies reveal favorable effects on macrophage polarization, cytokine signaling, extracellular matrix turnover, and thermogenesis, suggesting potential relevance to lipedema biology. Translational evidence from related fibro-inflammatory conditions such as steatohepatitis and heart failure further supports its antifibrotic and immunomodulatory plausibility. Although direct clinical evidence in lipedema is lacking, the convergence of mechanistic pathways provides a strong rationale to investigate tirzepatide as a disease-modifying candidate. If future clinical studies confirm these mechanisms, tirzepatide could represent a novel metabolic–hormonal therapy capable of modifying the natural course of lipedema. 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

Obesity is a multifactorial metabolic disease characterized by chronic low-grade inflammation, extracellular matrix (ECM) dysfunction, and systemic metabolic dysregulation. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are key regulators of ECM remodeling and inflammation in obesity. This narrative review aimed to synthesize and critically discuss current evidence on the effects of bariatric surgery and pharmacological therapies, including GLP-1 and dual GLP-1/GIP receptor agonists, on MMP activity and metabolic outcomes. Literature from PubMed and Scopus and Web of Science (2015–2024) was analyzed, focusing on studies evaluating MMPs, inflammation, and metabolic parameters. Bariatric surgery consistently reduces MMP-9 levels and normalizes MMP-2 activity, contributing to improved ECM integrity, reduced inflammation, and enhanced insulin sensitivity. Pharmacological therapies achieve substantial weight loss and glycemic control, but evidence regarding their direct effects on MMP activity remains limited. This review highlights bariatric surgery as the most effective strategy for modulating obesity-related MMP dysregulation and emphasizes the need for further research into the mechanistic effects of modern pharmacotherapy on ECM remodeling. Full article