Combined Treatment Research Articles

Synergistic effects of thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy in breast cancer management: an orthotopic mouse model study.

Liposome formulations of the cancer drug doxorubicin have been developed to address the severe side effects that result from administration of this drug in a conventional formulation. Among them, thermosensitive liposomal doxorubicin presents enhanced tumor targeting and efficient drug release when combined with mild hyperthermia localized to the tumor site. Exploiting the radiosensitizing benefits of localized thermal therapy, the integration of radiation therapy with the thermally activated liposomal system is posited to amplify the anti-tumor efficacy. This study explored a synergistic therapeutic strategy that combines thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy, using an orthotopic murine model of breast cancer. The protocol of sequential multi-modal treatment, incorporating low-dose chemotherapy and radiotherapy, substantially postponed the progression of primary tumor growth in comparison to the application of monotherapy at elevated dosages. Improvements in unheated distant lesions were also observed. Furthermore, the toxicity associated with the combination treatment was comparable to that of either thermosensitive liposome treatment or radiation alone at low doses. These outcomes underscore the potential of multi-modal therapeutic strategies to refine treatment efficacy while concurrently diminishing adverse effects in the management of breast cancer, providing valuable insight for the future refinement of thermosensitive liposomal doxorubicin applications.

Physicochemical Characteristics of Beef Meatballs at Various Post Mortem Phases with the Addition of Seaweed Flour (Gracillaria sp.)

The post-mortem phase of meat influences the physicochemical quality of the beef meatballs produced. The post mortem phase is the phase that meat goes through after slaughter. The post mortem phase is divided into 3, namely prerigor, rigor mortis and post rigor. Seaweed (Gracillaria sp.) can be used as a natural chewy meatball. This research aims to determine the best treatment combination between the post-mortem phase of meat and the addition of seaweed flour on the physicochemical characteristics and preferences of beef meatballs. This research used a completely randomized design with a factorial pattern with 2 factors with two replications. Factor I is the post mortem phase (pre-rigor, rigormortis and post-rigo). Factor II is the addition of seaweed flour (3%, 4% and 5%). The observation data were analyzed using ANOVA, if there were significant differences, the Duncan Multiple Range Test was carried out at the 5% level. The best treatment results were pre-rigor beef treatment with the addition of 5% seaweed flour, producing meatballs with characteristics of 69.05% water content, 2.93% ash content, 1.55% fat, 12.49% protein, 12.92N elasticity level, 47.22% water holding capacity. , Color preference level 4 (like really), aroma 4.07 (like really), taste 4.17 (like really) and texture 4.50 (like really).

A community proactive health management model for family doctors in Shandong, China.

Background Chronic disease management is an essential part of public health management and a fundamental means of slowing down the progression of major diseases. Unlike traditional medical care, proactive health management focuses on the combination of prevention and treatment. Proactive health management can reduce the re-admission rate of patients with chronic diseases, improve long-term prognosis, and effectively reduce the disability and mortality rates of major health events. This study aimed to establish a proactive health management model based on a grid-based medical service team arrangement, and to explore the effect of this model on managing chronic diseases in community health service institutions. Methods A grid-based medical service team was established in Binzhou, Shandong, China, consisting of general practitioners, nurses, public health doctors, health promoters and community grid liaison staff. Each team was responsible for several areas to monitor critical populations within the grid and compile statistics on the health management of these key populations in 2022-2023. Results A total of 2050 patients with coronary artery disease, 4973 patients with hypertension, and 1621 patients with type 2 diabetes were followed up in 2022. Compared with 155,612 resident health records in 2022, the number of records increased by 140.50% in 2023. The number of patients with hypertension under health management in 2023 increased by 50.92%; patients with type 2 diabetes increased by 74.65%; and the number of coronary artery disease increased by 42.00%. After the implementation of grid management, the hospitalisation rate for patients with type 2 diabetes significantly decreased in 2023 (P P >0.05). Conclusion The grid-based community proactive health management model makes full use of the advantages of community resources and improves the pertinence and coverage of community health services. Moreover, it reduces hospitalisation for patients with type 2 diabetes.

Investigation of the synergistic effect mechanism underlying sequential use of palbociclib and cisplatin through integral proteomic and glycoproteomic analysis.

Chemoresistance largely hampers the clinical use of chemodrugs for cancer patients, combination or sequential drug treatment regimens have been designed to minimize chemotoxicity and resensitize chemoresistance. In this work, the cytotoxic effect of cisplatin was found to be enhanced by palbociclib pretreatment in HeLa cells. With the integration of liquid chromatography-mass spectrometry-based proteomic and N-glycoproteomic workflow, we found that palbociclib alone mainly enhanced the N-glycosylation alterations in HeLa cells, while cisplatin majorly increased the different expression proteins related to apoptosis pathways. As a result, the sequential use of two drugs induced a higher expression level of apoptosis proteins BAX and BAK. Those altered N-glycoproteins induced by palbociclib were implicated in pathways that were closely associated with cell membrane modification and drug sensitivity. Specifically, the top four frequently glycosylated proteins FOLR1, L1CAM, CD63, and LAMP1 were all associated with drug resistance or drug sensitivity. It is suspected that palbociclib-induced N-glycosylation on the membrane protein allowed the HeLa cell to become more vulnerable to cisplatin treatment. Our study provides new insights into the mechanisms underlying the sequential use of target drugs and chemotherapy drugs, meanwhile suggesting a high-efficiency approach that involves proteomic and N-glycoproteomic to facilitate drug discovery.

Photodynamic/photothermal pH-responsive mannose-based dimeric prodrug for synergistic overcoming the biological barriers to conquer multidrug resistance in MRSA

Methicillin-resistant Staphylococcus aureus (MRSA), recognized for its resistance, poses a formidable challenge to public health, primarily attributable to its biochemical resistant mechanisms, capacity to form protective biofilms, and capacity to evade macrophage surveillance. In response to this threat, we constructed a multifunctional pH-responsive dimeric prodrug based on mannose (MAN) and cinnamaldehyde (CMA). This prodrug, designated as MACA@indocyanine green (ICG), incorporates the photosensitizer ICG. The nanoscale properties and MAN units integrated into the MACA@ICG prodrug could promote effective binding with infectious microbes or MAN residues on mammalian cells. This specific interaction, corroborated by co-localization studies using confocal microscopy and flow cytometry, is crucial for initial bacterial binding, biofilm penetration, and macrophage-specific uptake, all of which are strategic in surmounting the biological barriers posed by MRSA. Following its targeted accumulation, MACA@ICG was demonstrated responsiveness to the acidic microenvironment of bacteria to release free CMA, a natural compound with antimicrobial properties. The drug release, synergistically coupled with the effects of photothermal therapy (PTT) and photodynamic therapy (PDT) showcased superior synergistic antibacterial efficacy both in vitro and in vivo. Therefore, MACA@ICG was verified remarkable capabilities in surmounting bacterial biological barriers and exceptional antibacterial efficiency through the combinational treatments of herbal components, PDT and PTT.

Research progress and challenges of stem cell therapy for ischemic stroke

Ischemic stroke is a significant global cause of death and disability. Currently, treatment options for acute ischemic stroke are limited to intravenous thrombolysis and mechanical recanalization. Therefore, novel neuroprotective strategies are imperative. Stem cell transplantation possesses the capabilities of differentiation, proliferation, neuronal replacement, nerve pathway reconstruction, secretion of nerve growth factors, and enhancement of the microenvironment; thus, it is a potential therapeutic approach for ischemic stroke. In addition, the immunomodulatory function of stem cells and the combined treatment of stem cells and exosomes exhibit a favorable protective effect on brain injury and neurological dysfunction following stroke. Meanwhile, the theory of microbiota-gut-brain axis provides us with a novel perspective for comprehending and managing neurological diseases. Lastly, stem cell transplantation has demonstrated promising outcomes not only in treating ischemic stroke but also in dealing with other neurological disorders, such as brain tumors. Furthermore, challenges related to the tissue source, delivery method, immune response, and timing of transplantation still need to be addressed to optimize the treatment.

Assessing Treatments to Mitigate End-Face Cracking in Air-Dried Acacia dealbata Logs

Acacia dealbata Link, known as Mimosa in Portugal, is an invasive hardwood species with potential for construction use, but research is limited. The available stock of small-diameter juvenile wood logs can help reduce this gap, but tangential cracking at log ends challenges fastener connections. This study evaluated different treatments to control and reduce end-face cracking in small wood logs during air drying, an economical and environmentally friendly procedure. The extreme two-thirds of sixteen Mimosa logs were subjected to two treatments: one with longitudinal kerfs 15 mm deep along the length (two and three kerfs) and the other with a hollow in the center up to half the length (16 mm and 30 mm diameters). Over 219 days of air drying and compared with the central part, kerfing treatments significantly reduced outer-wood tangential cracking (p < 0.001), with the three kerfs also reducing crack numbers (p < 0.05) but increasing significantly cracks near the pith (p < 0.01). The 30 mm central hollow significantly reduced central perforation cracking (p < 0.05). Prospectively, the results suggest that a combined treatment approach involving cross-cuts could help reduce and/or control end cracking, thereby improving the suitability of wild Mimosa logs for construction use.

Assessing Treatments to Mitigate End-Face Cracking in Air-Dried Acacia dealbata Logs

Acacia dealbata Link, known as Mimosa in Portugal, is an invasive hardwood species with potential for construction use, but research is limited. The available stock of small-diameter juvenile wood logs can help reduce this gap, but tangential cracking at log ends challenges fastener connections. This study evaluated different treatments to control and reduce end-face cracking in small wood logs during air drying, an economical and environmentally friendly procedure. The extreme two-thirds of sixteen Mimosa logs were subjected to two treatments: one with longitudinal kerfs 15 mm deep along the length (two and three kerfs) and the other with a hollow in the center up to half the length (16 mm and 30 mm diameters). Over 219 days of air drying and compared with the central part, kerfing treatments significantly reduced outer-wood tangential cracking (p < 0.001), with the three kerfs also reducing crack numbers (p < 0.05) but increasing significantly cracks near the pith (p < 0.01). The 30 mm central hollow significantly reduced central perforation cracking (p < 0.05). Prospectively, the results suggest that a combined treatment approach involving cross-cuts could help reduce and/or control end cracking, thereby improving the suitability of wild Mimosa logs for construction use.

Success of Combination Therapy with Isavuconazole in a Pediatric Patient with Breakthrough Invasive Aspergillosis

AbstractThe increasing incidence of invasive fungal infections, coupled with the growing population of immunocompromised patients, has led to an increased need for antifungal agents. The newest azole, isavuconazole, plays an important role in the treatment of invasive aspergillosis in adults due to its broad spectrum, tolerability, and no need for therapeutic drug monitoring. This agent, which has not yet been approved for use in children, has significant problems with drug supply in Türkiye. We present the treatment response to isavuconazole combination therapy used in salvage treatment in a patient with breakthrough invasive aspergillosis, who had treatment failure with different antifungal combination treatment options and surgical resection.

Memory effects of prior subculture may impact the quality of multiomic perturbation profiles

Mass spectrometry-based omics technologies are increasingly used in perturbation studies to map drug effects to biological pathways by identifying significant molecular events. Significance is influenced by fold change and variation of each molecular parameter, but also by multiple testing corrections. While the fold change is largely determined by the biological system, the variation is determined by experimental workflows. Here, it is shown that memory effects of prior subculture can influence the variation of perturbation profiles using the two colon carcinoma cell lines SW480 and HCT116. These memory effects are largely driven by differences in growth states that persist into the perturbation experiment. In SW480 cells, memory effects combined with moderate treatment effects amplify the variation in multiple omics levels, including eicosadomics, proteomics, and phosphoproteomics. With stronger treatment effects, the memory effect was less pronounced, as demonstrated in HCT116 cells. Subculture homogeneity was controlled by real-time monitoring of cell growth. Controlled homogeneous subculture resulted in a perturbation network of 321 causal conjectures based on combined proteomic and phosphoproteomic data, compared to only 58 causal conjectures without controlling subculture homogeneity in SW480 cells. Some cellular responses and regulatory events were identified that extend the mode of action of arsenic trioxide (ATO) only when accounting for these memory effects. Controlled prior subculture led to the finding of a synergistic combination treatment of ATO with the thioredoxin reductase 1 inhibitor auranofin, which may prove useful in the management of NRF2-mediated resistance mechanisms.

Success of Combination Therapy with Isavuconazole in a Pediatric Patient with Breakthrough Invasive Aspergillosis

AbstractThe increasing incidence of invasive fungal infections, coupled with the growing population of immunocompromised patients, has led to an increased need for antifungal agents. The newest azole, isavuconazole, plays an important role in the treatment of invasive aspergillosis in adults due to its broad spectrum, tolerability, and no need for therapeutic drug monitoring. This agent, which has not yet been approved for use in children, has significant problems with drug supply in Türkiye. We present the treatment response to isavuconazole combination therapy used in salvage treatment in a patient with breakthrough invasive aspergillosis, who had treatment failure with different antifungal combination treatment options and surgical resection.

Research progress and challenges of stem cell therapy for ischemic stroke

Ischemic stroke is a significant global cause of death and disability. Currently, treatment options for acute ischemic stroke are limited to intravenous thrombolysis and mechanical recanalization. Therefore, novel neuroprotective strategies are imperative. Stem cell transplantation possesses the capabilities of differentiation, proliferation, neuronal replacement, nerve pathway reconstruction, secretion of nerve growth factors, and enhancement of the microenvironment; thus, it is a potential therapeutic approach for ischemic stroke. In addition, the immunomodulatory function of stem cells and the combined treatment of stem cells and exosomes exhibit a favorable protective effect on brain injury and neurological dysfunction following stroke. Meanwhile, the theory of microbiota-gut-brain axis provides us with a novel perspective for comprehending and managing neurological diseases. Lastly, stem cell transplantation has demonstrated promising outcomes not only in treating ischemic stroke but also in dealing with other neurological disorders, such as brain tumors. Furthermore, challenges related to the tissue source, delivery method, immune response, and timing of transplantation still need to be addressed to optimize the treatment.

Memory effects of prior subculture may impact the quality of multiomic perturbation profiles

Mass spectrometry-based omics technologies are increasingly used in perturbation studies to map drug effects to biological pathways by identifying significant molecular events. Significance is influenced by fold change and variation of each molecular parameter, but also by multiple testing corrections. While the fold change is largely determined by the biological system, the variation is determined by experimental workflows. Here, it is shown that memory effects of prior subculture can influence the variation of perturbation profiles using the two colon carcinoma cell lines SW480 and HCT116. These memory effects are largely driven by differences in growth states that persist into the perturbation experiment. In SW480 cells, memory effects combined with moderate treatment effects amplify the variation in multiple omics levels, including eicosadomics, proteomics, and phosphoproteomics. With stronger treatment effects, the memory effect was less pronounced, as demonstrated in HCT116 cells. Subculture homogeneity was controlled by real-time monitoring of cell growth. Controlled homogeneous subculture resulted in a perturbation network of 321 causal conjectures based on combined proteomic and phosphoproteomic data, compared to only 58 causal conjectures without controlling subculture homogeneity in SW480 cells. Some cellular responses and regulatory events were identified that extend the mode of action of arsenic trioxide (ATO) only when accounting for these memory effects. Controlled prior subculture led to the finding of a synergistic combination treatment of ATO with the thioredoxin reductase 1 inhibitor auranofin, which may prove useful in the management of NRF2-mediated resistance mechanisms.

Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells.

The rise of drug resistance in cancer cells presents a formidable challenge in modern oncology, necessitating the exploration of innovative therapeutic strategies. This review investigates the latest advancements in overcoming drug resistance mechanisms employed by cancer cells, focusing on emerging therapeutic modalities. The intricate molecular insights into drug resistance, including genetic mutations, efflux pumps, altered signaling pathways, and microenvironmental influences, are discussed. Furthermore, the promising avenues offered by targeted therapies, combination treatments, immunotherapies, and precision medicine approaches are highlighted. Specifically, the synergistic effects of combining traditional cytotoxic agents with molecularly targeted inhibitors to circumvent resistance pathways are examined. Additionally, the evolving landscape of immunotherapeutic interventions, including immune checkpoint inhibitors and adoptive cell therapies, is explored in terms of bolstering anti-tumor immune responses and overcoming immune evasion mechanisms. Moreover, the significance of biomarker-driven strategies for predicting and monitoring treatment responses is underscored, thereby optimizing therapeutic outcomes. For insights into the future direction of cancer treatment paradigms, the current review focused on prevailing drug resistance challenges and improving patient outcomes, through an integrative analysis of these emerging therapeutic strategies.

Atorvastatin exerts a preventive effect against steroid-induced necrosis of the femoral head by modulating Wnt5a release.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent form of osteonecrosis in young individuals. More efficacious clinical strategies must be used to prevent and treat this condition. One of the mechanisms through which SONFH operates is the disruption of normal differentiation in bone marrow adipocytes and osteoblasts due to prolonged and extensive use of glucocorticoids (GCs). In vitro, it was observed that atorvastatin (ATO) effectively suppressed the impact of dexamethasone (DEX) on bone marrow mesenchymal stem cells (BMSCs), specifically by augmenting their lipogenic differentiation while impeding their osteogenic differentiation. To investigate the underlying mechanisms further, we conducted transcriptome sequencing of BMSCs subjected to different treatments, leading to the identification of Wnt5a as a crucial gene regulated by ATO. The analyses showed that ATO exhibited the ability to enhance the expression of Wnt5a and modulate the MAPK pathway while regulating the Wnt canonical signaling pathway via the WNT5A/LRP5 pathway. Our experimental findings provide further evidence that the combined treatment of ATO and DEX effectively mitigates the effects of DEX, resulting in the upregulation of osteogenic genes (Runx2, Alpl, Tnfrsf11b, Ctnnb1, Col1a) and the downregulation of adipogenic genes (Pparg, Cebpb, Lpl), meanwhile leading to the upregulation of Wnt5a expression. So, this study offers valuable insights into the potential mechanism by which ATO can be utilized in the prevention of SONFH, thereby holding significant implications for the prevention and treatment of SONFH in clinical settings.

Enhancement of engineering properties of cement mortars with masonry construction and demolition fines via carbon dioxide utilization, storage and chemical treatment

Shortage of natural sand is severely affecting the global construction industry. The construction sector also generates a substantial amount of construction and demolition (C&D) waste of which masonry wastes constitute a major fraction. Using a circular economy approach, this article explores the feasibility of using treated masonry waste fines (MWF) to replace 75 % of natural sand in Portland cement-based mortars. The treatment consists of a combination of acid washing and CO2 curing to improve the engineering properties of MWF-cement mortars. 0.1 mol/L and 0.5 mol/L (M) H2SO4 were used for chemical treatment of the MWF followed by CO2 curing at 50,000 ppm for 4 hours. Mortars containing treated MWF (MWF-0.1 M-C and MWF-0.5 M-C) were subject to conventional curing (moist curing followed by dry curing at 30 ◦C and 65 % RH) and carbon sequestration via accelerated carbonation curing. Experimental findings suggest that combined treatment with acid and CO2 reduces the pore volume by 13 – 27 % in the pore size range of 10 – 100 nm in MWF. Consequently, mortars with MWF-0.1 M-C and MWF-0.5 M-C show 29 – 30.50 % higher compressive strength at 28-d age and a 29 – 36 % reduction in total shrinkage compared to mortars with similar dosages of as-received MWF. This ensures statistically similar strength and shrinkage as that of the plain mortar (with 100 % natural sand), demonstrating the potential for 75 % sand replacement using treated MWF. Furthermore, carbon sequestration of 16.40 – 19 % by mass of Portland cement is achieved, which contributes to a 15 % enhancement in early strength and reduces the mesoporous volume and shrinkage by up to 43 % and 15–19 % respectively. In summary, the research offers a pathway to recover a “new sand” from C&D wastes , which could be used to manufacture masonry construction products with reduced demand for natural sand.

Polymyxin B neurotoxicity as manifestation of a serious life-threatening adverse reaction: clinical case

The aim of this work is to describe a clinical case of a serious life-threatening adverse reaction in the form of neurotoxicity (convulsions, apnea requiring mechanical ventilation) to the polymyxin B drug, and also to remind that manifestations of neurotoxicity can be extremely varied and nonspecific, and do not occur after every administration, can be delayed, require vigilance and careful monitoring both from the attending physicians and from anesthesiologistsresuscitators, neurologists, ophthalmologists, etc.A 62-year-old female patient diagnosed with stage IIIB T4G3N0M0 pleomorphic soft tissue sarcoma of the right thigh, condition after combination treatment, developed infection and necrosis of the postoperative wound (recto-abdominal flap). According to the results of a microbiological study and an antibiogram, the patient received polymyxin B as part of combination antibacterial therapy. On days 4, 5, 6, 7 of polymyxin administration, the patient experienced the following symptoms in various combinations: weakness, numbness of the face, paresthesia, paresis of the limbs, partial convulsions, respiratory depression, and apnea.After establishing a connection between neurologicalsymptoms and intravenous administration of polymyxin B (the total score on the Naranjo scale was 6 points, the degree of reliability of the “adverse reaction–drug” relationship was probable) and drug withdrawal, manifestations of neurotoxicity completely disappeared and did not reoccur. The patient was discharged in satisfactory condition.In a patient with symptoms of damage to the nervous system, it is necessary to conduct multiple differential diagnostic search to exclude stroke, epilepsy, encephalitis, hereditary and acquired neurodegenerative diseases, as well as side effects of medications. At the slightest suspicion of the likelihood of an adverse reaction to polymyxin B/colistimethate sodium, the Naranjo algorithm must be used to establish a cause-and-effect relationship between the adverse reaction and the drug.

PARP inhibition with rucaparib alone followed by combination with atezolizumab: Phase Ib COUPLET clinical study in advanced gynaecological and triple-negative breast cancers.

Combining PARP inhibitors (PARPis) with immune checkpoint inhibitors may improve clinical outcomes in selected cancers. We evaluated rucaparib and atezolizumab in advanced gynaecological or triple-negative breast cancer (TNBC). After identifying the recommended dose, patients with PARPi-naive BRCA-mutated or homologous recombination-deficient/loss-of-heterozygosity-high platinum-sensitive ovarian cancer or TNBC received rucaparib plus atezolizumab. Tumour biopsies were collected pre-treatment, during single-agent rucaparib run-in, and after starting combination therapy. The most common adverse events with rucaparib 600 mg twice daily and atezolizumab 1200 mg on Day 1 every 3 weeks were gastrointestinal effects, fatigue, liver enzyme elevations, and anaemia. Responding patients typically had BRCA-mutated tumours and higher pre-treatment tumour levels of PD-L1 and CD8 + T cells. Markers of DNA damage repair decreased during rucaparib run-in and combination treatment in responders, but typically increased in non-responders. Apoptosis signature expression showed the reverse. CD8 + T-cell activity and STING pathway activation increased during rucaparib run-in, increasing further with atezolizumab. In this small study, rucaparib plus atezolizumab demonstrated acceptable safety and activity in BRCA-mutated tumours. Increasing anti-tumour immunity and inflammation might be a key mechanism of action for clinical benefit from the combination, potentially guiding more targeted development of such regimens. ClinicalTrials.gov (NCT03101280).

Regulation of Proline Accumulation and Protein Secretion in Sorghum under Combined Osmotic and Heat Stress.

Plants reprogramme their proteome to alter cellular metabolism for effective stress adaptation. Intracellular proteomic responses have been extensively studied, and the extracellular matrix stands as a key hub where peptide signals are generated/processed to trigger critical adaptive signal transduction cascades inaugurated at the cell surface. Therefore, it is important to study the plant extracellular proteome to understand its role in plant development and stress response. This study examined changes in the soluble extracellular sub-proteome of sorghum cell cultures exposed to a combination of sorbitol-induced osmotic stress and heat at 40 °C. The combined stress significantly reduced metabolic activity and altered protein secretion. While cells treated with osmotic stress alone had elevated proline content, the osmoprotectant in the combined treatment remained unchanged, confirming that sorghum cells exposed to combined stress utilise adaptive processes distinct from those invoked by the single stresses applied separately. Reactive oxygen species (ROS)-metabolising proteins and proteases dominated differentially expressed proteins identified in cells subjected to combined stress. ROS-generating peroxidases were suppressed, while ROS-degrading proteins were upregulated for protection from oxidative damage. Overall, our study provides protein candidates that could be used to develop crops better suited for an increasingly hot and dry climate.

Efficacy and safety of the combination or monotherapy with GLP-1 receptor agonists and SGLT-2 inhibitors in Type 2 diabetes mellitus: An update systematic review and meta-analysis

PurposeTo evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter2(SGLT-2) inhibitors and glucagon-like peptide-1(GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM). MethodsTo construct an exhaustive database of randomized controlled trials (RCTs) concerning SGLT-2 inhibitors and GLP-1 agonists, a methodical search was undertaken across a range of databases, such as Embase, PubMed, and the Cochrane Central Register of Controlled Trials, from their inception to January 2023. Following this, a meta-analysis was executed to amalgamate the collected data, which allowed for the calculation of standardized mean differences (SMDs), odds ratios (ORs), and 95 % confidence intervals (CIs) for a spectrum of outcomes. This analytical approach was designed to yield a quantitative evaluation of the therapeutic efficacy and safety profile of SGLT-2 inhibitors and GLP-1 agonists for the treatment of diabetes mellitus. ResultsWhen compared to GLP-1 agonist therapy alone, the combination therapy did not significantly reduce fasting plasma glucose (FPG) levels (95 % confidence interval [CI]: -0.27, 0.10; p = 0.35), body weight (95 % CI: -0.18, 0.18; p = 1.00), Glycosylated Hemoglobin, Type A1C (HbA1c) (95 % CI: -0.29, 0.07; p = 0.22), or systolic blood pressure (SBP) values (95 % CI: -0.29, 0.06; p = 0.21). In contrast, when compared to SGLT-2 inhibitor therapy alone, combination therapy significantly decreased FPG by 0.24 mmol/L (95 % CI: -0.43, -0.05; p = 0.01), HbA1c by 0.45 % (95 % CI: -0.72, -0.18; p = 0.001), and SBP by 0.12 mmHg (95 % CI: -0.24, 0.00; p = 0.05). However, the combination therapy failed to demonstrate a significant reduction in body weight when compared with either SGLT-2 inhibitor therapy (95 % CI: -0.20, 0.05; p = 0.24) or GLP-1 agonist therapy (95 % CI: -0.18, 0.18; p = 1.00). Additionally, the combination therapy did not increase the incidence of hypoglycemia. It should be noted that data regarding mortality and cardiovascular outcomes were limited. ConclusionsThe combination treatment of SGLT-2 inhibitors and GLP-1 receptor agonists effectively reduces HbA1c, FPG, and SBP without elevating the risk of hypoglycemia when compared to monotherapy with SGLT-2 inhibitors. However, these beneficial effects were not observed when the combination therapy was compared with GLP-1 receptor agonist treatment alone.