Search Results (1,148)

A total of 640 one-day-old Cobb 500 MV × Cobb 500 FF mixed broilers were randomly assigned to one of four experimental treatments with four replicates per treatment and 40 birds per replicate for 32 days. The treatments consisted of a basal diet (control group), basal diet + 0.02% zinc bacitracin (AGP group), basal diet + 0.2% G. lucidum powder (GLP; 0.2% GLP group), and basal diet + 0.3% GLP (0.3% GLP group). The results showed that dietary 0.2% GLP supplementation increased body weight compared to the control and 0.3% GLP groups, and decreased feed conversion ratio (FCR) compared to the control group, during 19–32 days (p < 0.05). The feed intake was lower (p < 0.05) in both dietary GLP supplementation groups and the AGP group during 1–8 and 1–32 days compared to the control group. Additionally, the FCR was lower in the dietary GLP supplementation group (0.2%) and the AGP group (p < 0.05) compared to the control group. Moreover, the caeca of broiler chickens in the AGP and 0.2% GLP groups had a higher abundance of lactic acid bacteria (LAB). Supplementation of feed additives (AGP and GLP) increased the relative weight of the thymus, with no effect on the bursa of Fabricius and spleen. However, AGP supplementation decreased the serum IgM concentration, while supplementing a higher dose of GLP (0.3%) increased the ash content in the tibia. The findings indicate that 0.2% GLP is the recommended supplementation dose as a natural growth promoter to replace AGP in apparently normal chickens. Full article

Glucagon-like peptide-1 (GLP-1) receptor agonists are currently available for the management of type 2 diabetes mellitus. They have been shown to help with diabetic kidney diseases through multiple mechanisms. In this review, we will shed light on the different mechanisms of action through which GLP-1 receptor agonists may achieve their roles in renal protection in diabetics, both in animal and human studies, as well as review the renal outcomes when using these drugs and their safety profile in diabetic patients. Full article

This study investigated the effects of Fructus Aurantii extract (FAE) on growth performance, nutrient apparent digestibility, serum parameters, fecal microbial composition, and short-chain fatty acids (SCFAs) in finishing pigs. In total, 75 Duroc × Landrace × Yorkshire pigs (equally divided by sex), with an initial body weight of 79.49 ± 4.27 kg, were randomly assigned to three treatment groups. The pigs were fed either a basic diet (CON) or a basal diet supplemented with 500 mg/kg of FAE (FAE500) and 1000 mg/kg of FAE (FAE1000). The FAE1000 group exhibited a significantly higher final body weight (FBW) (p < 0.05), and the average daily feed intake (ADFI) showed an increasing tendency in the FAE500 and FAE1000 groups (p = 0.056) compared to the CON group. Additionally, the inclusion of FAE resulted in the significantly higher apparent digestibility of crude ash (Ash), gross energy (GE), and crude protein (CP) (p < 0.05), with a tendency to the increased digestibility of dry matter (DM) (p = 0.053). Dietary FAE supplementation led to elevated serum levels of reduced glutathione (GSH) and decreased levels of serum L-lactic dehydrogenase (LDH), along with a tendency to increase serum glucose (GLU) levels (p = 0.084). The FAE500 group demonstrated higher serum concentrations of motilin (MTL) and gastrin (GAS) (p < 0.05), and a tendency for reduced serum glucagon-like peptide-1 (GLP-1) level (p = 0.055) compared to the CON group. Furthermore, alpha diversity analysis revealed that the FAE500 group significantly increased the Chao 1 and Observed_species indexes (p < 0.05). Similarly, beta diversity analysis indicated that FAE feeding altered the fecal microbial structure (p = 0.083). Notably, compared with the control group, CF231, Pediococcus, and Mogibacterium displayed higher relative abundance in the feces of the FAE500 group, whereas Tenericutes showed a reduction in relative abundance (p < 0.05). Additionally, the relative abundance of Tenericute was negatively correlated with the digestibility of DM, GE, Ash, and CP (p < 0.05). Serum MTL and GAS levels correlated positively with the Coprococcus, Dorea, Pediococcus, and Mogibacterium relative abundances (p < 0.05). Collectively, dietary FAE supplementation could enhance growth performance by boosting beneficial bacteria in feces, stimulating gastrointestinal hormone secretion, and improving nutrient digestibility. Full article

Background/Objectives: Glucagon-like peptide-1 (GLP-1) receptor is currently one of the most explored targets exploited for the management of diabetes and obesity, with many aspects of its mechanisms behind cardiovascular protection yet to be fully elucidated. Research dedicated towards the development of oral GLP-1 therapy and non-peptide ligands with broader clinical applications is crucial towards unveiling the full therapeutic capacity of this potent class of medicines. Methods: This study describes the virtual screening of a natural product database consisting of 695,133 compounds for positive GLP-1 allosteric modulation. The database, obtained from the Coconut website, was filtered according to a set of physicochemical descriptors, then was shape screened against the crystal ligand conformation. This filtered database consisting of 26,325 compounds was used for virtual screening against the GLP-1 allosteric site. Results: The results identified ten best hits with the XP score ranging from −9.6 to −7.6 and MM-GBSA scores ranging from −50.8 to −32.4 and another 58 hits from docked pose filter and a second round of XP docking and MM-GBSA calculation followed by molecular dynamics. The analysis of results identified hits from various natural products (NPs) classes, to whom attributed antidiabetic and anti-obesity effects have been previously reported. The results also pointed to β-lactam antibiotics that may be evaluated in drug repurposing studies for off-target effects. The calculated ADMET properties for those hits revealed suitable profiles for further development in terms of bioavailability and toxicity. Conclusions: The current study identified several NPs as potential GLP-1 positive allosteric modulators and revealed common structural scaffolds including peptidomimetics, lactams, coumarins, and sulfonamides with peptidomimetics being the most prominent especially in indole and coumarin cores. Full article

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used to treat obesity and diabetes but are linked to a variety of gastrointestinal (GI) adverse events (AEs). Real-world data on GLP-1 RA-related GI AEs and outcomes are limited. This study assessed GI AEs and adverse outcomes using the US FDA Adverse Event Reporting System (FAERS). Methods: This retrospective pharmacovigilance study used the US FDA FAERS database (2007–2023). We searched GLP-1 RA medications, AEs, and adverse outcomes. Demographic, treatment indication, and AE data were collected. Descriptive analysis involved frequencies and percentages, while reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and multivariate logistic regression were used to analyze GLP-1 RA-related GI AEs and outcomes. Results: From 2007 to 2023, a total of 187,757 AEs were reported with GLP-1 RAs, and 16,568 were GLP-1 RA-associated GI AEs in the US. Semaglutide was linked to higher odds of nausea (IC₀₂₅: 0.151, β_Coeff: 0.314), vomiting (IC₀₂₅: 0.334, β_Coeff: 0.495), and delayed gastric emptying (IC₀₂₅: 0.342, β_Coeff: 0.453). Exenatide was associated with pancreatitis (IC₀₂₅: 0.601, β_Coeff: 0.851) and death (ROR: 4.50, IC₀₂₅: 1.101). Overall, semaglutide had a broader range of notable adverse effects; by comparison, dulaglutide and liraglutide use was associated with fewer significant GI AEs. Conclusions: Analysis of the FAERS data reveals that GLP-1 RAs, particularly semaglutide and exenatide, are significantly associated with specific GI AEs, such as nausea, vomiting, delayed gastric emptying, and pancreatitis. Clinicians should be aware of these potential risks to ensure optimal monitoring and patient safety. This study demonstrated the utility of pharmacovigilance data in identifying safety signals, which can inform future pharmacoepidemiological investigations to confirm causal relationships. Clinicians should be aware of these potential risks to ensure optimal monitoring and patient safety. Full article

Numerous compounds involved in the regulation of the cardiovascular system are also engaged in the control of metabolism. This review gives a survey of literature showing that arginine vasopressin (AVP), which is an effective cardiovascular peptide, exerts several direct and indirect metabolic effects and may play the role of the link adjusting blood supply to metabolism of tissues. Secretion of AVP and activation of AVP receptors are regulated by changes in blood pressure and body fluid osmolality, hypoxia, hyperglycemia, oxidative stress, inflammation, and several metabolic hormones; moreover, AVP turnover is regulated by insulin. Acting on V1a receptors in the liver, AVP stimulates glycogenolysis, reduces synthesis of glycogen, and promotes fatty acid synthesis and acetyl CoA carboxylase activity. Stimulating V1b receptors in the pancreatic islands, AVP promotes release of insulin and glucagon-like peptide-1 (GLP-1) and potentiates stimulatory effects of glucose and ACTH on secretion of insulin. Simultaneously, insulin increases AVP secretion by neurons of the paraventricular nucleus and the supraoptic nucleus. There is strong evidence that secretion of AVP and its metabolic effectiveness are significantly altered in metabolic and cardiovascular diseases. Both experimental and clinical data indicate that inappropriate interactions of AVP and insulin play an important role in the development of insulin resistance in obesity and diabetes mellitus. Full article

Isoflavones are composed of phytoestrogens (genistein and daidzein), which can be metabolized by cats. These compounds can promote the maintenance of lean body mass and control food intake. These effects are desirable in neutered animals, as they are predisposed to obesity. The objective of this study was to evaluate the effects of dietary supplementation of 1.0% isoflavone on the metabolizable energy intake, serum concentrations of satiety-related hormones and peptides, and body composition of neutered cats. Sixteen neutered adult cats were blocked by gender and divided into two groups (n = 8): the control group (CG) received a commercial diet, while the isoflavone group (IG) received the same diet supplemented by 1% of isoflavone for 99 days. Computed tomography was performed on the first and last experimental days to assess the animals’ body composition. Satiety challenges were conducted on days 19 and 44. In the last day of the study, blood samples were collected to determine the concentration of insulin, ghrelin, leptin, peptide YY, and GLP-1. A statistical analysis was conducted using R software 3.5.2, considering both the interaction and individual effects of group and time (p < 0.05). The average intake of genistein in the IG was 0.75 ± 0.10 mg/kg body weight, and daidzein intake was 51.73 ± 7.05 mg/kg. No significant individual or interaction effects were observed for any of the analyzed variables. Therefore, the inclusion of 1.0% isoflavone in the diet did not affect the energy requirements, satiety responses, or body composition of neutered adult cats. Full article

Background: SGLT-2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1RA) have demonstrated nephro- and cardioprotective effects, but their neuroprotective properties, especially concerning stroke severity, and mechanisms are not unambiguous. We aimed to study the influence of SGLT-2i with different selectivity and GLP-1RA on brain damage volume and neurological status in non-diabetic and diabetic rats and to investigate the underlying mechanisms. Methods: Non-diabetic Wistar rats were divided into five groups (n = 10 each) and received empagliflozin, canagliflozin, or dulaglutide as study drugs and metformin as comparison drug. Control animals were administered 0.9% NaCl for 7 days before stroke. At 48 h after stroke, we assessed neurological deficit, neuronal and astroglial damage markers, and brain damage volume. We also modeled type 2 DM in Wistar rats using the high-fat diet+nicotinamide/streptozotocin method and established similar treatment groups. After 8 weeks, rats were subjected to stroke with further neurological deficit, neuroglial damage markers, and brain necrosis volume measurement. Results: In non-diabetic rats, all the drugs showed an infarct-limiting effect; SGLT-2i and dulaglutide were more effective than metformin. DULA improved neurological status compared with MET and SGLT-2i treatment. All the drugs decreased neurofilament light chains (NLCs) level and neuronal damage markers, but none of them decreased the glial damage marker S100BB. In DM, similarly, all the drugs had infarct-limiting effects. Neurological deficit was most pronounced in the untreated diabetic rats and was reduced by all study drugs. All the drugs reduced NLC level; dulaglutide and empagliflozin, but not canagliflozin, also decreased S100BB. None of the drugs affected neuron-specific enolase. Conclusions: SGLT-2i and GLP-1RA are neuroprotective in experimental stroke. GLP-1RA might be more effective than SGLT-2i as in non-diabetic conditions it influences both brain damage volume and neurological status. All study drugs decrease neuronal damage, while GLP-1RA and highly selective SGLT-2i EMPA, but not low-selective CANA, also have an impact on neuroglia in diabetic conditions. Full article

Background/Objectives: Type 2 diabetes and weight loss are associated with detrimental skeletal health. Incretin-based therapies (GLP-1 receptor agonists, and dual GIP/GLP-1 receptor agonists) are used clinically to treat diabetes and obesity. The potential effects of semaglutide and tirzepatide on bone metabolism in type 2 diabetic mice remain uncertain. Methods: Combined streptozotocin and high fat feeding were employed in female C57BL/6J mice to promote hyperglycemia. Mice were administered for 4 weeks with a saline vehicle (sc., once-daily), semaglutide (40 μg/kg/d, sc., every three days), or tirzepatide (10 nmol/kg, sc., once-daily). Bone strength was assessed by three-point bending. Femur microarchitecture was determined by micro-CT, and bone formation and resorption parameters were measured by histomorphometric analysis. Serum was collected to measure bone resorption (C-telopeptide fragments of type I collagen, CTX) and formation (procollagen type 1 N-terminal propeptide, P1NP) biomarkers, respectively. The expression of bone metabolism-related genes was evaluated in the bone using RT-PCR. Results: Glucose levels significantly reduced after 4 weeks of semaglutide and tirzepatide treatment (both p < 0.05) compared with vehicle treatment. Tirzepatide led to more weight loss than semaglutide. Compared to saline-treated diabetic mice, the mean femur length was shorter in the tirzepatide group. After treatment with tirzepatide or semaglutide, cortical bone and trabecular bone parameters did not change significantly compared to saline-treated diabetic mice, except that cortical thickness was lower in the semaglutide group compared to the saline group (p = 0.032). Though CTX and P1NP levels decreased, however, the change in CTX and P1NP levels did not differ among the four groups during the 4 weeks of treatment (all p > 0.05). Semaglutide affected RANKL and OPG mRNA expression and increased the ratio of OPG/RANKL. No significant difference was found in the quantity of Col1a1, RANKL, OPG, and RUNX2 between tirzepatide- and saline-treated diabetic mice. Conclusions: The 4-week treatment with semaglutide and tirzepatide had a neutral effect on bone mass compared with the controls, and most of the bone microarchitecture parameters were also comparable between groups in diabetic mice. A better understanding of incretin-based therapies on bone metabolism in patients with diabetes requires further evaluation in large clinical trials. Full article

Chronic respiratory disorders are the third leading cause of mortality globally. Consequently, there is a continuous pursuit of effective therapies beyond those currently available. The therapeutic potential of the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide/GLP-1 (GIP/GLP-1) receptor agonists extends beyond the regulation of glycemia, including glucometabolic, cardiovascular, and renal effects, rendering them viable candidates, due to their mechanisms of action, for the possible treatment of respiratory disorders. This manuscript aims to provide a comprehensive evaluation of the evidence on potential direct (cellular) and indirect (metabolic) actions of GLP-1 and GIP/GLP-1 receptor agonists within the pulmonary systems. In addition, it examines their efficacy in addressing prevalent respiratory disorders, specifically chronic obstructive pulmonary disease (COPD), asthma, pneumonia, obstructive sleep apnea, pulmonary hypertension, lung cancer, and lung transplantation. Finally, the manuscript seeks to identify potential avenues for further focused research in this field. Full article

Introduction: Diabetes mellitus (DM) has a millennia-long history, with early references dating back to ancient Egypt and India. However, it was not until the 20th century that the connection between diabetes and insulin was fully understood. The sequencing of insulin in the 1950s initiated the convergence of biotechnology and diabetes management, leading to the development of recombinant human insulin in 1982. This marked the start of peptide-based therapies in DM. Recombinant peptides for DM treatment: Numerous recombinant peptides have been developed since, starting with modified insulin molecules, with the aim of bettering DM management through fine-tuning the glycemic response to insulin. Peptide-based therapies in DM have expanded substantially beyond insulin to include agonists of Glucagon-like peptide-1 receptor and Glucose-dependent insulinotropic polypeptide receptor, glucagon receptor antagonists, and even peptides exerting multiple receptor agonist effects, for better metabolic control. Insulin pumps, continuous glucose monitoring, and automated insulin delivery systems: The development of modern delivery systems combined with real-time glucose monitoring has significantly advanced diabetes care. Insulin pumps evolved from early large devices to modern sensor-augmented pumps with automated shutoff features and hybrid closed-loop systems, requiring minimal user input. The second-generation systems have demonstrated superior outcomes, proving highly effective in diabetes management. Islet cell transplantation, organoids, and biological pancreas augmentation represent innovative approaches to diabetes management. Islet cell transplantation aims to restore insulin production by transplanting donor beta cells, though challenges persist regarding graft survival and the need for immunosuppression. Organoids are a promising platform for generating insulin-producing cells, although far from clinical use. Biological pancreas augmentation relies on therapies that promote beta-cell (re)generation, reduce stress, and induce immune tolerance. Further biotechnology-driven perspectives in DM will include metabolic control via biotechnology-enabled tools such as custom-designed insulin hybrid molecules, machine-learning algorithms to control peptide release, and engineering cells for optimal peptide production and secretion. Full article

The objective of this study was to evaluate the effects of dietary addition of lactic acid and glutamine, and their interactions, on growth performance, nutrient digestibility, digestive enzyme activity, intestinal barrier functions, microflora, and expressions of intestinal development-related genes of weaning piglets. Ninety-six 24-day-old weaning piglets (Duroc × Landrace × Yorkshire, weaned at 21 ± 1 d and fed the basal diet for a 3 d adaptation period) with initial body weight of 7.24 ± 0.09 kg were randomly assigned to one of four dietary treatments with six replicates per treatment and four pigs per replicate in a 2 × 2 factorial treatment arrangements: (1) CON (a 2-period basal diet; control), (2) LS (supplemented with 2% lactic acid), (3) GS (supplemented with 1% glutamine), and (4) LGS (supplemented with 2% lactic acid and 1% glutamine). The study lasted for 28 d. On days 25–28, fresh fecal samples were collected to evaluate apparent total tract digestibility (ATTD) of nutrients. After 28 d, one weaning pig per pen was euthanized, and physiological samples obtained. Results showed that the supplementation of lactic acid improved the ADFI of the pigs (p < 0.05), while the pigs fed the glutamine diet had a greater ADFI and higher G/F (p < 0.05), and there were significant interactive effects between lactic acid and glutamine on the ADFI and G/F of the pigs (p < 0.05). The ATTD of CP and ash for pigs fed with lactic acid was significantly enhanced, and pigs fed the glutamine diet had greater ATTD of CP and ash (p < 0.05), while there were significant interactive effects between lactic acid and glutamine on the ATTD of CP and ash of the pigs (p < 0.05). Pigs fed with lactic acid exhibited greater activity of α-amylase and lipase (p < 0.05); moreover, the activity of lipase in the pigs showed a significant interactive effect between lactic acid and glutamine (p < 0.05). There was a greater villus height and villus height to crypt depth ratio in pigs fed with lactic acid (p < 0.05), and the villus height to crypt depth ratio of pigs fed with glutamine was greater (p < 0.05). There were greater GLUT2, IGF-1, TGF-β2, OCLN, and ZO-1 mRNA levels in pigs fed with lactic acid (p < 0.05), and the supplementation of glutamine increased SGLT1, GLUT2, PepT1, IGF-1, IGF-1R, TGFβ-2, GLP-2, and OCLN mRNA levels (p < 0.05), Additionally, expressions of SGLT1, GLUT2, PepT1, IGF-1, IGF-1R, TGFβ-2, GLP-2, CLDN-2, OCLN, and ZO-1 mRNA levels of pigs showed a positive interactive effect between lactic acid and glutamine (p < 0.05). Supplementation of lactic acid significantly increased the populations of Bifidobacterium in cecal digesta, Lactobacillus in colonic digesta, and the content of butyric acid in colonic digesta (p < 0.05). In addition, there were significant interactive effects between lactic acid and glutamine on populations of Bifidobacterium in cecal digesta, Lactobacillus in colonic digesta, and the content of acetic acid, butyric acid, and total VFAs in cecal digesta of the pigs (p < 0.05). Collectively, the current results indicate that dietary supplementation with lactic acid and glutamine had a positive synergistic effect on weaning pigs, which could improve growth performance through promoting the development of the small intestine, increasing digestive and barrier function, and regulating the balance of microflora in pigs, and which might be a potential feeding additive ensemble to enhance the health and growth of weaning piglets in the post-antibiotic era. Full article

Background: Emerging evidence supports cannabidiol (CBD) as a promising therapeutic compound for various health conditions, despite its approval as a medication (product for medical purposes) remaining restricted to a limited range of clinical indications. Simultaneously, the regulation of cannabis-derived products for medicinal and recreational use has expanded their global market availability to meet local community demands. This scenario presents a complex challenge for clinicians, researchers, and industry, as the global appeal of therapeutic uses of CBD is growing more rapidly than the scientific evidence supporting its safety and effectiveness. Outcomes: A narrative review was conducted to discuss the best evidence regarding the pharmacological profile of CBD, its efficacy, and safety within the context of regulation and perspectives on the development of new cannabinoid-based drugs. Key articles addressing the various facets of this issue were selected for comprehensive analysis. Conclusions: Clinicians and researchers may face unique challenges in understanding the pharmacological profile of CBD and the prospects for developing its clinical indications, given the heterogeneity of clinical terminologies and the quality and composition of cannabis-based medical products available on the market. More basic and clinical research that complies with regulatory agencies’ testing guidelines, such as good manufacturing practices (GMPs), good laboratory practices (GLPs), and good clinical practices (GCPs), is needed to obtain approval for CBD or any other cannabinoid as a therapeutic for broader clinical indications. Full article

Cannabinoids are emerging as promising treatments for inflammatory diseases such as ulcerative colitis. Specifically, cannabinoid 2 (CB2) receptors, which are upregulated during inflammation, have been distinctively linked to anti-inflammatory and analgesic effects. HU308, a synthetic cannabinoid developed to activate CB2 receptors selectively, aims to minimize unwanted off-target side effects. This study evaluated the effectiveness of both cannabidiol (CBD) and HU308 in mouse models of dextran sodium sulphate (DSS)-induced colitis, which mimic the acute and chronic phases of ulcerative colitis. Mice were treated with DSS in drinking water (four percent for the acute model and one to two percent for the chronic model) to induce colitis, as indicated by increased disease activity index (DAI) scores and inflammatory markers. Treatment with 60 mg/kg of CBD, but not lower doses, significantly reduced colitis symptoms, such as inflammation, cytokine levels, and MPO activity, while also normalizing glucagon-like peptide-1 (GLP-1) levels. HU308 showed comparable efficacy to high-dose CBD (60 mg/kg) but at a much lower dose (2.5 mg/kg), without observable toxicity. HU308 effectively normalized DAI scores, colon inflammation, ammonia levels, and GLP-1 expression in both colitis models. These results suggest that both CBD and HU308 are promising treatments for ulcerative colitis. However, HU308 demonstrates enhanced therapeutic potential by achieving similar outcomes at a fraction of the dose required for CBD, reducing the risk of off-target side effects. The ability of HU308 to modulate GLP-1, a biomarker of gut endocrine function, further underscores its promise as a novel treatment option. Full article

The increasing prevalence of both type 2 diabetes mellitus and heart failure has underscored the urgent need for optimized therapeutic strategies that address the complex interplay between these conditions. Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a popular class of glucose-lowering agents due to their favorable glycemic effects, safety profile, and potential cardiovascular benefits. However, the impact of DPP-4 inhibitors on heart failure outcomes in patients with diabetes remains contentious, with conflicting evidence from clinical trials and observational studies. This review critically examines current evidence on the use of DPP-4 inhibitors in patients with coexisting diabetes and heart failure, focusing on pharmacodynamics, safety, and efficacy outcomes. We explore the physiological mechanisms by which DPP-4 inhibitors may influence heart failure risk, including modulation of inflammation, oxidative stress, and myocardial fibrosis. Clinical trials such as SAVOR-TIMI 53, EXAMINE, and TECOS are evaluated to provide a comprehensive analysis of DPP-4 inhibitors’ effects on hospitalization for heart failure, mortality, and cardiovascular events in diabetic patients. While some trials suggest an increased risk of HF hospitalizations with specific DPP-4 inhibitors (e.g., saxagliptin), others report neutral effects, raising questions about the class effects versus individual drug characteristics within this group. Additionally, we address discrepancies in outcomes related to patient demographics, HF phenotype, and comorbid conditions that may influence DPP-4 inhibitors’ risk–benefit profile. Comparative insights into alternative glucose-lowering therapies such as SGLT2 inhibitors and GLP-1 receptor agonists are also provided, highlighting potential implications for treatment selection in this high-risk population. In summary, this review synthesizes available evidence on DPP-4 inhibitors’ impact in diabetic patients with heart failure, aiming to guide clinicians in making informed therapeutic decisions. While DPP-4 inhibitors remain a viable option in diabetes management, caution is warranted in patients with advanced heart failure, and future research is essential to refine patient-specific guidelines. Full article