Rybelsus (semaglutide oral) / Novo Nordisk - LARVOL DELTA

Editorial: Global Obesity Rates Continue to Rise with Challenges for New Drug Treatments Including GLP-1 Receptor Agonists. (PubMed, Med Sci Monit) - "The US Food and Drug Administration (FDA) has recently accepted a new drug application for oral semaglutide, which, if approved, will be the first oral drug authorized for long-term weight management...Increasing demands and drug costs also drive the production of compounded versions (copycat drugs), which have escalated for GLP-1 receptor agonists, with products without quality and safety evaluation. This editorial aims to provide an update on the global challenges of increasing rates of obesity and the demands for therapeutic approaches to weight loss, including GLP-1 receptor agonists."

Journal • Genetic Disorders • Obesity

Sema-RTx: Semaglutide Treatment for Hyperglycaemia After Renal Transplantation (clinicaltrials.gov) - P4 | N=104 | Recruiting | Sponsor: Rigshospitalet, Denmark | Trial completion date: Apr 2026 ➔ Dec 2027 | Trial primary completion date: Apr 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Nephrology • Transplantation

Clinical Effectiveness of Oral Semaglutide in Women with Type 2 Diabetes: A Nationwide, Multicentre, Retrospective, Observational Study (Women_ENDO2S-RWD Substudy). (PubMed, Nutrients) - " oSEMA was effective and safe in WWT2D in a real-world setting, with nearly one-third of patients reporting weight loss >10% and more than two-thirds achieving HbA1c < 7%. oSEMA showed no sex bias in terms of effectiveness and safety."

Journal • Observational data • Retrospective data • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Drugs and devices for weight management. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Oral semaglutide in HFpEF: Real-world evidence and causal considerations. (PubMed, Eur J Intern Med) - No abstract available

HEOR • Journal • Real-world evidence • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Type 2 Diabetes Mellitus

The SOUL trial: a new era for oral semaglutide in reducing cardiovascular risk in high-risk patients with diabetes (PubMed, G Ital Cardiol (Rome)) - No abstract available

Journal • Cardiovascular • Diabetes • Metabolic Disorders

A multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice (PIONEER REAL Japan): Subgroup analyses. (PubMed, J Diabetes Investig) - "HbA1c and body weight decreased across all subgroups, providing insights into oral semaglutide use in clinical practice for individuals with different characteristics in the real-world setting."

Journal • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effect of semaglutide versus placebo on cardiorenal outcomes by prior cardiovascular disease and baseline body mass index: Pooled post hoc analysis of SUSTAIN 6 and PIONEER 6. (PubMed, Diabetes Obes Metab) - P3 | "Semaglutide treatment improved cardiorenal outcomes versus placebo in people with T2D, regardless of prior CVD and baseline BMI. This improvement was observed even when accounting for changes in BW, indicating direct effects of semaglutide on the cardiorenal system. This analysis supports the broad efficacy of semaglutide in a diverse T2D population."

Journal • Retrospective data • Cardiovascular • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Heart Failure • Metabolic Disorders • Myocardial Infarction • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Oral absorption of semaglutide: pharmacokinetic modeling and molecular dynamics simulations. (PubMed, In Silico Pharmacol) - "Semaglutide is a GLP-1 receptor agonist that is formulated for oral administration as Rybelsus®...This work shows the potential for using molecular modeling in parameterization of pharmacokinetic models for molecules in which conformational variability may influence the pharmacokinetics. The online version contains supplementary material available at 10.1007/s40203-025-00393-7."

Journal • PK/PD data

First-in-Class Oral Dual GLP-1/Glucagon Agonist for Patients with Obesity and Metabolic Disorders: In Vivo Pharmacokinetic and Pharmacodynamic Results (ENDO 2025) - "These half-lives were found to be comparable to the reported half-lives of approved oral semaglutide, Rybelsus®, and support a once daily oral OXM treatment regimen. In conclusion, the systemic bioavailability and pharmacologic response, combined with the extended biological half-life of the molecule obtained in rats and minipigs, support further development of oral tablets of OPK-88006 as a potentially first-in-class dual GLP-1/glucagon agonist for the treatment of obesity and metabolic syndromes. A Phase 1 clinical study of this novel oral peptide candidate is currently being planned."

Late-breaking abstract • PK/PD data • Preclinical • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity

Identifying Late Autoimmune Diabetes in Older Adults: Implications for Diagnosis and Management (ENDO 2025) - "He was previously managed with Metformin 2000 mg daily and Semaglutide po 7 mg daily with good control of his sugars. This case highlights the importance of considering LADA even in elderly patients who present with unexplained worsening of diabetes. Given LADA's potential for atypical presentation, clinicians should maintain a high level of clinical suspicion in patients who exceed the typical age of presentation."

Clinical • Cushing’s Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Immunology • Metabolic Disorders • Pain • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Impact of Sleeping Habits on the Weight Loss Effect of Oral Glucagon-Like Peptide-1 Receptor Agonists Among Obese Patients: An Observational Study in Japan. (PubMed, Cureus) - "This study aimed to determine the impact of sleeping habits on the weight loss effect of semaglutide, an oral GLP-1 RA, among Japanese individuals with obesity...Participants who exhibited improvements in sleeping time or sleep quality during the treatment period were considered to have experienced sufficient treatment effects. These findings suggest that getting enough sleep may improve the weight loss effect of GLP-1 RAs in real-world settings."

Journal • Observational data • Genetic Disorders • Obesity

Comparison of the Safety, Efficacy and Pharmacokinetics of DehydraTECH -CBD and DehydraTECH-GLP1 Agonists Alone or in Combination, in Overweight or Obese, Pre- and Type 2 Diabetic Participants (clinicaltrials.gov) - P1 | N=148 | Active, not recruiting | Sponsor: Lexaria Bioscience Corp. | Recruiting ➔ Active, not recruiting | N=80 ➔ 148

Enrollment change • Enrollment closed • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Impact of GLP-1 receptor agonists on upper gastrointestinal endoscopy: an updated systematic review and meta-analysis. (PubMed, Surg Endosc) - "This updated systematic review and meta-analysis found a significant association between GLP-1 RA use and increased GRC. While GLP-1 RA use was linked to higher rates of aborted procedures, no difference in aspiration events was observed between the two groups. Notably, our study identified a protective effect of concurrent colonoscopy on GRC among GLP-1 RA users, while no significant differences were found in GRC risk among different GLP-1 RA agents. Further prospective studies are needed to control for potential confounders and better assess the true impact of GLP-1 RA use on EGD outcomes."

Journal • Retrospective data • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Infectious Disease • Metabolic Disorders • Obesity • Pneumonia • Respiratory Diseases • RAS

Oral vs. Subcutaneous Semaglutide in Type 2 Diabetes Mellitus (clinicaltrials.gov) - P=N/A | N=212 | Completed | Sponsor: University of Palermo

New trial • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 23-26 October 2023 (European Medicines Agency) - "EMA’s safety committee (PRAC) has concluded that the available evidence does not support a causal association between the Glucagon-Like Peptide-1 Receptor Agonists (GLP-1) - exenatide, liraglutide, dulaglutide, semaglutide, and lixisenatide - and cancer of the thyroid (a small gland in the front and lower part of the neck which makes and releases hormones)....The MAHs for liraglutide- (including Victoza, Saxenda, Xultophy), semaglutide- (including Ozempic, Rybelsus, Wegovy), exenatide- (including Bydureon, Byetta), dulaglutide- (i.e.Trulicity) and lixisenatide- (including Lyxumia, Suliqua) containing products should continue to monitor these events closely, including any new publications, as part of their pharmacovigilance activities and report any new evidence on this issue in their Periodic Safety Update Reports (PSURs)."

European regulatory • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 2-5 June 2025 (European Medicines Agency) - "EMA’s safety committee (PRAC) has concluded its review of medicines containing semaglutide following concerns regarding a possible increased risk of developing non-arteritic anterior ischemic optic neuropathy (NAION), an eye condition that may cause loss of vision. Semaglutide, a GLP-1 receptor agonist, is the active substance in certain medicines used in the treatment of diabetes and obesity (namely Ozempic, Rybelsus and Wegovy). After reviewing all available data on NAION with semaglutide, PRAC has recommended that the product information for semaglutide medicines is updated to include NAION as a side effect with a frequency of ‘very rare’ (it may affect up to 1 in 10,000 people). If patients experience a sudden loss of vision or rapidly worsening eyesight during treatment with semaglutide, they should contact their doctor without delay. If NAION is confirmed, treatment with semaglutide should be stopped."

PRAC • Obesity

Incretin-based therapies for the treatment of obesity-related diseases. (PubMed) - "Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development...Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD. Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the underlying mechanism, whether involving direct effects on target tissues or mediated by improvement in BW, glucose levels and other CV risk factors."

Journal • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Obstructive Sleep Apnea • Osteoarthritis • Pain • Respiratory Diseases • Rheumatology • Sleep Disorder • Type 2 Diabetes Mellitus

Attention Healthcare professionals: WHO Issues Safety Alert on Semaglutide Use (Medical Dialogues) - "The World Health Organization (WHO) has issued a global safety alert highlighting the risk of non-arteritic anterior ischemic optic neuropathy (NAION) associated with the use of semaglutide-containing medicines, including Ozempic, Rybelsus, and Wegovy. These widely prescribed drugs are used for the management of type 2 diabetes and obesity....The alert follows a recent review by the European Medicines Agency (EMA), which recommended updating product information for these medicines to include NAION as a very rare side effect....In parallel, the WHO Advisory Committee on Safety of Medicinal Products (ACSoMP), during its May 2025 meeting, recommended revising the Risk Management Plan for semaglutide to include NAION and any necessary pharmacovigilance measures. The WHO noted that it has received individual case safety reports (ICSRs) of NAION following semaglutide administration from multiple countries through VigiBase, the global adverse event database."

Commercial • Obesity • Type 2 Diabetes Mellitus

Association of semaglutide with less limb events in people with type 2 diabetes and peripheral artery disease or foot ulcers: An observational study comparing matched cohorts. (PubMed, Diabetes Obes Metab) - "Among people with type 2 diabetes and PAD or foot ulcers, the use of semaglutide was associated with a significantly lower risk of major limb events than other GLTs."

Journal • Observational data • Cardiovascular • Diabetes • Metabolic Disorders • Peripheral Arterial Disease • Type 2 Diabetes Mellitus

New onset diabetic retinopathy with glucagon-like peptide-1 receptor agonists: A case report. (PubMed, J Am Pharm Assoc (2003)) - "This case highlights a progressive decline in retinal health despite well-controlled T2D and the possible contribution of GLP-1RA therapy to DR progression. Switching to GLP-1RA agents with potentially lower risk for DR, such as oral semaglutide, may be beneficial when patients develop DR on GLP1-RA therapy. Further studies that evaluate the risk of DR while using GLP-1RA therapy, as well as the risk across the GLP1-RA class, are needed. Additional guidance on managing possible new onset or worsening DR on GLP-1RA therapy is especially necessary."

Journal • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Genetic Disorders • Metabolic Disorders • Obesity • Ophthalmology • Retinal Disorders • Type 2 Diabetes Mellitus

Reporting on the real-world safety and effectiveness of oral semaglutide in improving glycemic control and reducing cardiovascular risk: a letter to the editor. (PubMed, Minerva Endocrinol (Torino)) - No abstract available

Journal • Real-world evidence • Cardiovascular

Non-insulin therapies in the inpatient management of type 2 diabetes, safety and effectiveness of a start-stop protocol: the ENDOCARE ALC study (EASD 2025) - "Supported by Unrestricted Grant by Novonordisk Clinical Trial Registration Number: N/A Background and aims: The implementation of a clinical practice guideline for the integrated management of diabetes in the hospital setting, including therapies with benefits in terms of cardio-renal morbidity and mortality and their validation in real-world practice, will become a priority for any centre of excellence.Materials and Prospective observational study in a third level centre to evaluate health care outcomes according to a new guideline with a START-STOP protocol for the use of oral antidiabetic drugs (OAD) (including oral semaglutide (oSEMA) and SGLT2 inhibitors)...OADs used in G1 were: SGLT2 inhibitors (N 205), oSEMA (N 35), Metformin (N 56), DPP4 inhibitors (N 38)... The use of oral antidiabetic agents within a START-STOP protocol in PWT2D is safe and effective in routine clinical practice and hospital settings, and was associated with better metabolic control and lower..."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Impact of oral semaglutide on renal outcomes in type 2 diabetes: insights from a multicentre real-world cohort: Renal_ENDO2S-RWD substudy (EASD 2025) - "In a real-world setting, oral semaglutide treatment resulted in clinically meaningful reductions in albuminuria without changes in eGFR slope in PWT2D. Effectiveness, safety and tolerability were not influenced by CKD severity."

Clinical • Real-world • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effectiveness of semaglutide in oral vs subcutaneous injectable formulation: a UK real-world data from Association of British Clinical Diabetologists national audit (EASD 2025) - "Across the PIONEER programme, oral semaglutide demonstrated similar efficacy for reduction of HbA1c and weight compared with injectable liraglutide. Within the UK real-world setting, both oral and injectable semaglutide are effective to reduce HbA1c levels in people with type 2 diabetes. Compared with oral therapy, injectable semaglutide showed greater Hba1c reduction in these observational datasets. These findings support personalized treatment choices based on individual preferences and clinical need."

Clinical • Real-world • Real-world evidence • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus