Oral Insulin Breakthroughs In Development

INTRODUCTION

Diabetes is a chronic metabolic disorder primarily classified into two types: type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). T1DM, an autoimmune disease often diagnosed in adolescence, is marked by the body’s inability to produce insulin. In contrast, T2DM, which constitutes the majority of diabetes cases, is associated with insulin resistance and is typically diagnosed in adulthood. By 2030, the global prevalence of T2DM is expected to rise, primarily due to unhealthy lifestyle choices such as poor diet and lack of physical activity, leading to obesity. Insulin, a protein hormone, is crucial for diabetes management. While subcutaneous injections are the most common delivery method, they have limitations, including poor patient compliance and rapid insulin clearance. Noninvasive delivery methods, particularly oral administration, have been explored extensively but remain hindered by challenges related to insulin bioavailability in the gastrointestinal tract. Despite promising developments, oral insulin has yet to reach clinical application.

 

A BACKGROUND OF ORAL INSULIN RESEARCH

Research into oral insulin delivery has faced numerous challenges since the first attempts in 1921, shortly after insulin’s discovery. Early attempts at getting a viable delivery system, like giving patients insulin enterally or changing formulations by adding alcohol, did not lead to a better metabolic state. [14,15]. Despite setbacks, companies like Emisphere, Diabetology, and Oramed continued to develop oral insulin formulations, with clinical trials from 2001 to 2019 showing mixed results. Often, trials failed to demonstrate superior glycemic control over placebo, largely due to small sample sizes and challenges with insulin bioavailability. Some companies abandoned the development, but others pressed on, underscoring the continued ambition to make oral insulin a reality [16,17].

A key obstacle to oral insulin delivery is the gastrointestinal (GI) environment, which presents fluctuating pH levels and digestive enzymes that degrade insulin. The stomach, with a pH as low as 2.5, poses a significant threat to insulin stability, making enteric coatings essential for protection [18]. Additionally, enzymes such as pepsin in the stomach and trypsin in the small intestine cleave insulin into inactive peptides, complicating oral administration. Some formulations, like Oramed’s ORMD-0801, use proteinase inhibitors to protect insulin, but long-term concerns about enzyme inhibition remain [21,22].

The mucus lining of the GI tract further complicates drug absorption. This viscoelastic layer, composed mainly of water, mucin, and electrolytes, traps insulin molecules, preventing them from reaching epithelial cells for absorption. Researchers have explored mucosal adhesion systems using materials like chitosan (CS), a positively charged polysaccharide that interacts with the negatively charged mucus. This interaction increases insulin’s residence time, enhancing absorption, with preclinical studies showing promising improvements in insulin bioavailability [26–28].

Finally, the epithelial barrier, consisting of various cell types and tight junctions (TJs), also limits insulin absorption. Strategies aimed at opening TJs or using cell-penetrating peptides (CPPs) have resulted in modest improvements in bioavailability. However, risks associated with TJ disruption, such as immune responses, make these approaches less viable for long-term use. Although CPPs have doubled insulin’s transcellular transport, oral bioavailability remains low at 2.48%, highlighting the persistent challenges in oral insulin delivery [29–36].

 

A NEW APPROACH TO ORAL INSULIN DELIVERY

Recently, experts have started investigating new oral insulin delivery systems, focusing on the encapsulation of insulin within different types of nanoparticles to enhance its stability and absorption in the gastrointestinal (GI) tract. These systems were tested in preclinical models using animals like rats to assess their effectiveness in improving insulin bioavailability. Different formulations were explored, including lipid-based nanoparticles (such as solid lipid nanoparticles and nanostructured lipid carriers), polymeric nanoparticles (like chitosan-based systems and hydrogels), and inorganic nanoparticles (such as mesoporous silica and quantum dots). 

The studies assessed the ability of these carriers to protect insulin from degradation by stomach acid and enzymes, as well as their efficiency in facilitating insulin transport across the intestinal barrier. Key parameters evaluated included insulin encapsulation efficiency, bioavailability rates, and the impact on blood glucose levels in diabetic animals. Additionally, safety assessments were conducted in some cases, examining the potential toxicity of these carriers over long-term use.

 

TYPES OF NANOCARRIER-BASED ORAL INSULIN FORMULATIONS

Many nanocarrier-based oral insulin systems are currently being explored. Nanocarriers are tiny particles, often under 1000 nm in size, designed to protect insulin from degradation in the gastrointestinal (GI) tract and improve its absorption. These carriers can be classified into lipid-based, polymeric, and inorganic nanoparticles. Lipid-based nanoparticles, like solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), are advantageous for cellular uptake due to their lipid composition. Still, they face challenges with encapsulating hydrophilic molecules like insulin. Despite these challenges, some SLN formulations have achieved bioavailability rates of around 5% in animal studies [48].

Polymeric nanoparticles, another important category, use natural or synthetic polymers such as chitosan and poly(lactic-co-glycolic acid) (PLGA). The FDA has approved these polymers for their biocompatibility. Chitosan-based formulations, for instance, have shown promise due to their ability to interact with the mucus layer in the intestines and improve insulin absorption, achieving bioavailability rates of up to 18% in animal models [63]. Insulin can also be encapsulated with hydrogels and micelles. It provides sustained release and enhanced stability in the GI tract [68,70].

Inorganic nanoparticles, such as mesoporous silica nanoparticles (MSNs) and quantum dots (QDs), are also gaining traction in oral insulin delivery. These carriers offer exceptional drug-loading capacities and protection for insulin in the harsh GI environment. For example, MSNs modified with polyethylene glycol (PEG) have been reported to stabilize insulin and improve its bioavailability [74]. However, concerns about the long-term toxicity of inorganic nanoparticles remain, particularly regarding their effects on the liver, kidneys, and nervous system [75].

 

SURFACE MODIFICATION OF INSULIN NANOPARTICLES

Surface modifications of nanoparticles (NPs) have been explored to enhance the stability and absorption of oral insulin. Various strategies include using coatings, such as hydrogels and gelatin, which protect insulin in acidic environments. Hydrogels, for instance, have demonstrated the ability to control insulin release in diabetic mice, while gelatin-coated NPs maintain stability in gastric conditions [50, 90]. Additionally, pollen encapsulation techniques have been shown to significantly improve oral insulin bioavailability, leveraging the protective structure of pollen particles [92].

Adjusting the surface charge of NPs has also been investigated. Negatively charged NPs enhance mucus permeability, while positively charged ones prolong their presence in the mucus layer. Interestingly, studies have shown that surface charge only has a limited impact on insulin bioavailability, as negatively and positively charged NPs exhibited similar absorption rates in diabetic rats [79, 66]. Lastly, zwitterionic and protein-based modifications further improve NP permeability and stability, highlighting the importance of surface characteristics in oral insulin delivery systems [80, 81].

 

CLINICAL TRIALS ON ORAL INSULIN AND THEIR SUCCESS RATES

Several clinical trials have assessed the efficacy of different oral insulin formulations. Nodlin™, developed by NOD Pharmaceuticals, was one of the early formulations tested in a Phase I clinical trial. In 2012, this trial involved 12 healthy volunteers over four days and showed promising glucose-lowering effects. Nodlin’s performance was comparable to subcutaneously injected neutral protamine Hagedorn insulin, with a biopotency of 37%. However, the trial also exhibited high variability, with a standard deviation of 90%, indicating inconsistencies in its efficacy [119].

Another oral insulin formulation, HDV-I, developed by Diasome Pharmaceuticals, was designed to target liver cells. In a small clinical trial involving six patients with type 2 diabetes (T2DM), HDV-I demonstrated superior hypoglycemic effects compared to a placebo, particularly after breakfast. However, its impact on glycemic control after other meals was less pronounced, and its efficacy compared to subcutaneous insulin still needs to be discovered. Although a larger Phase II/III study began in 2008 with 230 patients, the results and recruitment status have yet to be published [120].

One of the most notable oral insulin candidates is Oramed’s ORMD-0801. Despite promising results in Phase II trials, where it achieved a 0.6% reduction in baseline HbA1c levels in patients with T2DM, the formulation failed to demonstrate significant efficacy in a larger Phase III trial. In 2023, with 710 participants, the trial found no significant improvement in glycemic control after 26 weeks of treatment compared to a placebo, highlighting the ongoing challenges in developing effective oral insulin [121, 122].

Overall, while initial trials have shown potential, the success of oral insulin in clinical settings has been limited. These results underscore the need for further research and refinement of delivery systems to overcome the current challenges associated with oral insulin formulations.

 

CURRENT PROGRESS AND CHALLENGES IN THE DEVELOPMENT OF ORAL INSULIN

Although significant progress has been made in developing oral insulin, several challenges remain before it can become a viable treatment. Initial trials, such as those involving Nodlin™ and HDV-I, showed some promise in lowering blood glucose levels. Still, issues like variability in efficacy and incomplete data from large-scale studies hinder conclusive results [119,120]. Despite encouraging Phase II outcomes, Oramed’s ORMD-0801 failed to demonstrate significant improvement in glycemic control in a recent Phase III trial, highlighting the difficulties in achieving consistent efficacy [121,122]. While some formulations have advanced to later-stage trials, reliable and effective oral insulin treatments are still not ready for widespread use.

 

CONCLUSION

The study concludes that significant clinical success remains elusive despite extensive research and innovative approaches to develop oral insulin, such as nanocarrier systems, oral microneedles, and gene therapy. While certain strategies have shown potential in targeting specific cells and improving oral bioavailability, clinical trials have yet to produce effective results. The failure of promising candidates in advanced trials underscores the ongoing challenges in creating a viable oral insulin delivery system, making it clear that more research is needed before it can become a practical treatment option for diabetes.

 

References

1.  [14] Mohajan, D., & Mohajan, H. K. (2023). The discovery of insulin is a great achievement for diabetes patients. Journal of Studies in Social Sciences & Humanities, 2, 8–16. (https://mpra.ub.uni-muenchen.de/113456/)

   

1. [15] Qi, J., Zhuang, J., Lv, Y., Lu, Y., & Wu, W. (2018). Exploiting or overcoming the dome trap for enhanced oral immunization and drug delivery. Journal of Controlled Release, 275, 92–106. (https://www.sciencedirect.com/science/article/pii/S0168365918310709)
2. [16] Harrison, G. A. (1923). Insulin in alcoholic solution by the mouth. British Medical Journal, 2, 1204. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2302093/)

 

1. [17] Heinemann, L., & Jacques, Y. (2009). Oral insulin and buccal insulin: A critical reappraisal. Journal of Diabetes Science and Technology, 3, 568–584. (https://journals.sagepub.com/doi/10.1177/193229680900300319)

 

1. [18] Wei, T., Thakur, S. S., Liu, M., & Wen, J. (2022). Oral delivery of glutathione: Antioxidant function, barriers and strategies. Acta Materia Medica, 2(1), 177–192. 

(https://www.atlantis-press.com/journals/amm/125955874)

 

1. [21] Choonara, B. F., Choonara, Y. E., Kumar, P., Bijukumar, D., du Toit, L. C., & Pillay, V. (2014).  A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules. Biotechnology Advances, 32 (6), 1269–1282. (https://www.sciencedirect.com/science/article/pii/S0734975014000893)

 

1. [22]Arbit, E., & Kidron, M. (2017). Oral insulin delivery in a physiologic context.Journal of Diabetes Science and Technology, 11 (5), 825–832. (https://journals.sagepub.com/doi/10.1177/1932296817701887)

 

1. [26] Ways, T. M. M., Lau, W. M., & Khutoryanskiy, V. V. (2018). Chitosan and its derivatives for application in mucoadhesive drug delivery systems. Polymers, 10 (3), 267. (https://www.mdpi.com/2073-4360/10/3/267)

 

1. [27] Zhang, Y., Wu, X., Meng, L., Zhang, Y., Ai, R., Qi, N., He, H., Xu, H., & Tang, X. (2012). Thiolated Eudragit nanoparticles for oral insulin delivery: Preparation, characterization and in vivo evaluation. International Journal of Pharmaceutics, 436 (1-2), 341–350. (https://www.sciencedirect.com/science/article/pii/S0378517312003995)

 

1. [28] Paone, P., & Cani, P. D. (2020).  Mucus barrier, mucins, and gut microbiota: The expected slimy partners? Gut, 69 (11), 2232–2243. (https://gut.bmj.com/content/69/11/2232)

 

1. [29] Capaldo, C. T., Powell, D. N., & Kalman, D. (2017).  Layered defense: How mucus and tight junctions seal the intestinal barrier. Journal of Molecular Medicine, 95 (9), 927–934. (https://link.springer.com/article/10.1007/s00109-017-1527-2)

 

1. [30] Lopes, M. A., Abrahim, B. A., Cabral, L. M., Rodrigues, C. R., Seiça, R. M. F., de Baptista Veiga, F. J., & Ribeiro, A. J. (2014).  Intestinal absorption of insulin nanoparticles: Contribution of M cells. Nanomedicine, 10 (6), 1139–1151. (https://www.sciencedirect.com/science/article/pii/S1549963414000991)

 

1.  [31] Anderson, J. M., & Van Itallie, C. M. (1995). Tight junctions and the molecular basis for regulation of paracellular permeability. American Journal of Physiology, 269 (3 Pt 1), G467–G475. (https://journals.physiology.org/doi/full/10.1152/ajpgi.1995.269.3.G467)

 

1. [32] Liu, C., Kou, Y., Zhang, X., Cheng, H., Chen, X., & Mao, S. (2018). Strategies and industrial perspectives to improve oral absorption of biological macromolecules. Expert Opinion on Drug Delivery, 15 (2), 223–233. (https://www.tandfonline.com/doi/full/10.1080/17425247.2018.1417071)

 

1. [33] Long, P., Zhang, Q., Xue, M., Cao, G., Li, C., Chen, W., Jin, F., Li, Z., Li, R., & Wang, X. (2019).  Tomato lectin-modified nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine: Targeting intestinal M cells following peroral administration. Biomedicine & Pharmacotherapy, 115, 108886. (https://www.sciencedirect.com/science/article/pii/S0753332219301912)

 

1. [34] McCartney, F., Gleeson, J. P., & Brayden, D. J. (2016). Safety concerns over the use of intestinal permeation enhancers: A mini-review. Tissue Barriers, 4 (1), e1176822. (https://www.tandfonline.com/doi/full/10.1080/21688370.2016.1176822)

 

1. [35] Böhmová, E., Machová, D., Pechar, M., Pola, R., Venclíková, K., Janoušková, O., & Etrych, T. (2018).  Cell-penetrating peptides: A useful tool for the delivery of various cargoes into cells. Physiological Research, 67 (Suppl 1), S267–S279. (https://www.biomed.cas.cz/physiolres/pdf/67/67_S267.pdf)

 

1. [36] Zhang, Y., Xiong, M., Ni, X., Wang, J., Rong, H., Su, Y., Yu, S., Mohammad, I. S., Leung, S. S. Y., & Hu, H. (2021).  Virus-mimicking mesoporous silica nanoparticles with an electrically neutral and hydrophilic surface to improve the oral absorption of insulin by breaking through dual barriers of the mucus layer and the intestinal epithelium. ACS Applied Materials & Interfaces, 13 (16), 18077–18088. (https://pubs.acs.org/doi/10.1021/acsami.0c22443)

 

1. [48] Hu, X., Fan, W., Yu, Z., Lu, Y., Qi, J., Zhang, J., Dong, X., Zhao, W., & Wu, W. (2016). Evidence does not support the absorption of intact solid lipid nanoparticles via oral delivery. Nanoscale, 8 (13), 7024–7035. (https://pubs.rsc.org/en/content/articlelanding/2016/nr/c6nr01583c)

 

1. [63] Maurya, A. K., Mishra, A., & Mishra, N. (2020). Nanoengineered polymeric biomaterials for drug delivery system. In Nanoengineered Biomaterials for Advanced Drug Delivery (pp. 109–143). Elsevier. (https://www.elsevier.com/books/nanoengineered-biomaterials-for-advanced-drug-delivery/maurya/978-0-12-818115-0)

 

1. [68] Yang, Y., Guo, Y., Xu, Y., Meng, Y., Zhang, X., Xia, X., & Liu, Y. (2020). Factors affecting the buccal delivery of deformable nanovesicles based on insulin–phospholipid complex: An in vivo investigation. Drug Delivery, 27 (1), 900–908. (https://www.tandfonline.com/doi/full/10.1080/10717544.2020.1828316)

 

1. [70] Bose, A., Roy Burman, D., Sikdar, B., & Patra, P. (2021). Nanomicelles: Types, properties, and applications in drug delivery. IET Nanobiotechnology, 15 (1), 19–27. (https://ietresearch.onlinelibrary.wiley.com/doi/10.1049/nbt2.12005)

 

1. [74] Andreani, T., de Souza, A. L. R., Kiill, C. P., Lorenzón, E. N., Fangueiro, J. F., Calpena, A. C., Chaud, M. V., Garcia, M. L., Gremião, M. P. D., & Silva, A. M. (2014). Preparation and characterization of PEG-coated silica nanoparticles for oral insulin delivery. International Journal of Pharmaceutics, 473 (1-2), 627–635. (https://www.sciencedirect.com/science/article/pii/S0378517314002902)

 

1. [75] Mohammadpour, R., Dobrovolskaia, M. A., Cheney, D. L., Greish, K. F., & Ghandehari, H. (2019). Subchronic and chronic toxicity evaluation of inorganic nanoparticles for delivery applications. Advanced Drug Delivery Reviews, 144, 112–132. (https://www.sciencedirect.com/science/article/pii/S0169409X19300551)

 

1. [50] Wu, H., Nan, J., Yang, L., Park, H. J., & Li, J. (2023). Insulin-loaded liposomes packaged in alginate hydrogels promote the oral bioavailability of insulin. Journal of Controlled Release, 353, 51–62. (https://www.sciencedirect.com/science/article/pii/S0168365923001257)

 

1. [90] Echave, M. C., Sánchez, P., Pedraz, J. L., & Orive, G. (2017). Progress of gelatin-based 3D approaches for bone regeneration. Pharmaceutics, 9 (2), 63–74. (https://www.mdpi.com/1999-4923/9/2/6)

 

1. [92] Lu, X., Li, J., Xue, M., Wang, M., Guo, R., Wang, B., & Zhang, H. (2023). Net-neutral nanoparticles-extruded microcapsules for oral delivery of insulin. ACS Applied Materials & Interfaces, 15 (28), 33491–33503. (https://pubs.acs.org/doi/10.1021/acsami.3c09566)

 

1. [79] Cheng, H., Cui, Z., Guo, S., Zhang, X., Huo, Y., & Mao, S. (2021). Mucoadhesive versus mucopenetrating nanoparticles for oral delivery of insulin. Acta Biomaterialia, 135, 506–519. (https://www.sciencedirect.com/science/article/pii/S1742706121000853)

 

1. [66] Wang, J., Kong, M., Zhou, Z., Yan, D., Yu, X., Cheng, X., Feng, C., Liu, Y., & Chen, X. (2017).  Mechanism of surface charge triggered intestinal epithelial tight junction opening upon chitosan nanoparticles for insulin oral delivery. Carbohydrate Polymers, 157, 596–602. (https://www.sciencedirect.com/science/article/pii/S0144861717307317)

 

1. [80] Shan, W., Zhu, X., Tao, W., Cui, Y., Liu, M., Wu, L., Li, L., Zheng, Y., & Huang, Y. (2016). Enhanced oral delivery of protein drugs using zwitterion-functionalized nanoparticles to overcome diffusion and absorption barriers. ACS Applied Materials & Interfaces, 8 (25), 25444–25453. (https://pubs.acs.org/doi/10.1021/acsami.6b07723)

 

1. [81] Han, X., Lu, Y., Xie, J., Zhang, E., Zhu, H., Du, H., Wang, K., Song, B., Yang, C., Shi, Y., & Cao, Z. (2020). Zwitterionic micelles efficiently deliver oral insulin without opening tight junctions. Nature Nanotechnology, 15 (8), 605–614. (https://www.nature.com/articles/s41565-020-0704-6)

 

1. [119] Li, J., Wang, Y., Han, L., Sun, X., Yu, H., & Yu, Y. (2012). Time–action profile of an oral enteric insulin formulation in healthy Chinese volunteers. Clinical Therapeutics, 34 (11), 2333–2338. (https://www.clinicaltherapeutics.com/article/S0149-2918(12)00797-7/fulltext)

 

1. [120] Geho, W. B., Rosenberg, L. N., Schwartz, S. L., Lau, J. R., & Gana, T. J. (2014). A single-blind, placebo-controlled, dose-ranging trial of oral hepatic-directed vesicle insulin add-on to oral antidiabetic treatment in patients with type 2 diabetes mellitus. Journal of Diabetes Science and Technology, 8 (4), 551–559. (https://journals.sagepub.com/doi/10.1177/193229681400800411)

 

1. [121] Eldor, R., Francis, B. H., Fleming, A., Neutel, J., Homer, K., Kidron, M., & Rosenstock, J. (2023). Oral insulin (ORMD-0801) in type 2 diabetes mellitus: A dose-finding 12-week randomized placebo-controlled study. Diabetes, Obesity & Metabolism, 25  (4), 943–952. (https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14936)

 

1. [122] Harris, E. (2023). Industry update. Therapeutic Delivery, 14 (2), 87–92. (https://www.futuremedicine.com/doi/full/10.2217/tde-2023-0006)

 

• Prognostic Scoring for Myelofibrosis
• Opioid Conversion Calculator
• Updated Advanced Opioid Conversion Calculator
• Nonsteroidal anti-inflammatory drugs (NSAID) Selection Tool
• Absolute Neutrophil Count Calculator
• Body Surface Area (BSA) Multi-Calc
• Carboplatin AUC Calculator
• Carboplatin AUC – Updated Version
• Urinary Indices, Renal Failure Index (RFI) and Fractional Excretion of Sodium (FE-NA)
• Creatinine Clearance (CRCL) – Standard Calculator
• Creatinine Clearance Multi-Calc – All of the latest research
• Patient Controlled Analgesia (PCA) Settings
• Intravenous Antineoplastic Agents – Administration Guidelines

---

Other

• Therapeutic Drug Levels
• Beers Criteria for potentially inappropriate medications
• Allergic response?  12-step desensitization protocol
• Protein requirements calculator
• Basal Metabolic Rate (BMR) Multi-calc (Estimate caloric requirements)
• Irritable Bowel Syndrome Treatment Options
• Common Anti-emetics
• Fall Assessment – Berg Balance Scale
• Topical Steroids Potency Selection Tool

---

Latest Research

• DFT And DTR Compete For Best Gastric Reconstruction Methods After Surgery
• Dental Extraction Prophylaxis Treatment With Antibiotics Is Controversial
• Oxymetazoline Successful Therapy To Improve Droopy Eye Appearance
• Exercise Tests To Detect Early Heart Failure Markers
• Attacking Heart Failure Inflammation With Prednisone
• Rusfertide Treatment For Elevated Red Blood Cell Production
• Stroke Victim Compliance With Prescription Medication
• Cardiac Arrest Wearable Detection Devices And Motivated Patient Compliance
• Superior Sinus Membrane Perforation Rates In Sinus Floor Elevation Procedures
• Surgical Success Of Crohn’s Disease Interventions
• Tau Accumulation And White Matter Changes Linked To Hypertension
• IBD Remission Communication To Promote Patient Comprehension
• Alzheimer’s Disease Revealed By Reliable Digital Memory Assessments
• (CCD) Cutaneous Crohn’s Disease Manifestations In The Pediatric Population
• Intestinal Obstruction Surgical Recovery ERAS Enhancements
• Antipsychotic Injectable Medications Deplete Neurotrophic Factor In Schizophrenia Patients
• The Fenofibrate Role In The Fight For Kidney Function Preservation
• Macroprolactinoma Early Detection Is A Vision Saving Strategy
• Flu Outbreaks And Crisis Management Solutions
• SIBO Pathology Risk In Intestinal Failure Patients
• Presyncope Patient Outcomes In Emergency Care
• When Cosmetic Procedures Go Wrong: Wounded Skin Emergencies
• Dementia Studies Reveal Home Foreclosure Is Associated With Memory Decline
• Colorectal Cancer And Risky Lifestyle Habits
• Constipation Relief In Adults Who Battle Comorbid Conditions
• Alcohol Use Increases Risk Of Falling and Head Trauma In Geriatric Population
• Miscarriage Study Reveals Predictive Factors For Successful Management
• Vaccination Gives Protection From the Flu And Improves Heart Attack Mortality Risk
• Muscular Dystrophy To Deplete Lean Body Muscle Mass And Destroy Motor Function
• Guselkumab Provides Relief For Patients Who Suffer With Psoriasis
• Tafamidis Reduces Mortality Rates In Cardiomyopathy Patients
• Dermatologic Emergency And Rates Of Admission To The Hospital
• Heart Transplant Patient Confessions About Life Quality
• Selexipag Therapy Effective For Pulmonary Hypertension Patients
• Devastating Impact Of Rheumatoid Arthritis Fatigue
• Methotrexate Accumulation In Patient Guts: Target Intestinal Mucosa Variation By Disease State
• Valoctocogene Roxaparvovec Gene Therapy Success Detailed For Hemophilia A Patients
• Efgartigimod Provides Genuine Benefit For Myasthenia Gravis Disease
• Bone Mineral Density In Menopause Patients: A Focus On Inflammation
• Hearing Loss And The Financial Advantage Of Cochlear Implantation
• Colitis Risk Increase In Inflammatory Eye Disease Patients
• Meibomian Gland Damaging By Glaucoma Treatments
• Erythropoietin Powerful Therapy For Anemia In Pregnant Patients
• Sjögren’s Disease Leads To Mental Health Meltdown
• Grape Syrup Improved Hemoglobin In Anemic Women
• Dermatitis: A Comprehensive Prevalence And Quality Of Life Study
• Morphea In Inflammation: Highest And Lowest Dermal Readings
• Thyroid Levels That Deviate From Normal Yield Sizable Risk For Macular Degeneration
• Pancreatic Cancer Patients Discover Weight Measurements Can Be Deceptive
• Astigmatism Is A Danger Of High BMI
• Mobile App Users Do Better Losing Weight
• Obesity Diminished: Patients Stay Aligned With Weight Loss Programs
• Weight Loss: Taking Action To See Results
• Birth Weight Abnormalities And The Pitfall Of Ongoing Childhood Weight Perception Errors
• Menopause Attitudes, Body Image, And Eating Disorders Affect Quality Of Life
• Burnout In Overwhelmed Healthcare Providers: A Tool For Risk Identification
• Sun Protection Is Saving Your Skin From Deadly Cancer
• Silica Dust: Does It Ignite Inflammation In The Gut And Eye
• Skin Cancer Incidence Highest In Patients Experiencing Adversity
• Dementia Risk Increase In Diabetic Patients With Poor Glycemic Control
• Colorectal Cancer Prognosis And Mortality Risk Improved By Eating Healthy Diet
• Beware – Gastric Cancer Protection Collapsed By Alcohol Intake
• Semaglutide Use Shows Bonus Benefit Of Osteoarthritis Risk Reduction
• Scoliosis In Adolescents Identified By Comprehensive AI Technology
• Osteoarthritis Pain Abatement By Focusing On Healthy Dietary Intake
• Corticosteroids In Osteoarthritis Therapy: Scarce Evidence For A Superior Drug And Dose
• Rotator Cuff Injury: Repair Strategy Benefits Of Gender Considerations
• Chronic Pain Management Utilizing Virtual Interfacing Is Successful At Symptom Reduction
• Pediatric Obesity Promoted By The Barrage Of Chemicals In The Environment
• The Male Infertility Battle: Exploiting Nonconventional Therapy
• Sperm DNA Fragmentation Risk Factors That Kill Potency
• Postpartum Hemorrhage Patients: Practical Research For Future Cardiovascular Events Risk
• Intranasal Vitamin B12 Is Promising Therapy For The Geriatric Population
• Poor Stroke Prognosis And Inadequate Vitamin D Levels: ​A Systematic Review And Meta-Analysis
• Dementia Linked To Inferior Nutrient Intake
• Aspirin Dosing Considerations In Essential Thrombocythemia: The ARES Trial
• Pediatric Brain Tumors: A Study To Document Patient Fatigue
• Dreadful Gastric Cancer And Mortality Risk After Diabetes Diagnosis
• Postpartum Hemorrhage To Reveal Increased Risk For Postpartum Depression 
• Brilliant Use Of Probiotic Medication To Treat Psoriasis
• Reconstruction Of Hand Is A Surgical Challenge After Extensive Skin Burn
• Latest Research Exploring Metformin Connection To Breast Cancer
• Can High Intensity Exercise Eliminate Migraine Headaches?
• Fatigue After Cancer And Cancer Survivors Confess Fears Of Recurrence
• Spotlight On Heart Failure Pathophysiology: Coronary Microvascular Dysfunction
• Colonoscopy Over Age 75 Is The Best Bet For Cancer Detection
• Blood Donation And Relief From Migraine Pain
• Ischemic Strokes Threaten Patients With Reversible Cerebral Vasoconstriction Syndrome
• Knee Surgery: A Meta Analysis Poised To Drive Down Surgical Site Infection Rates
• Kawasaki disease: Meta Analysis Reveals A Capable Steroid Combination Therapy
• Wound Healing After A Meningioma Resection: Risky And Dangerous Clinical Findings
• Light Therapy: A Promising Treatment Option For Infected Skin Ulcers
• UTI Quick Test: Using The Urine Flow Cytometer For Reduced Health System Burden
• Promising Anemia Treatment: Cooking With Sweet Basil Leaf
• Fatty Acid Intake And Reduced Cardiovascular Event Risk
• Skin Barrier Break Downs: Risk Factors In The Geriatric Population
• Oral Tranexamic Acid Treatment For Blushing Rosacea Patients Enhances Skin Barrier
• Bloody Surgery: Hospital Readmissions Blamed On Post-Op Anemia In Patients Undergoing Major Surgery
• Relugolix Combination Therapy To Improve Quality Of Life In Fibroid Patients
• Periodontitis Patients Likely To Suffer From Rheumatoid Arthritis Treatment
• Blood Culture Tests Reveal Fistula Infection In Febrile Patients
• Cardiac Troponins And Mortality Risk In Emergency Room Visits For Geriatric Falls
• Esophageal Cooling Proves Helpful For Injury Prevention During Cardiac Ablation
• Statin Therapy To Smash Cardiovascular Risk In Diabetic Patients
• Spotlight On Thyroid Function In Liver Disease Patients
• Acute Heart Failure: Measuring The Diversity Of Health Related Quality Of Life Markers

---

---