semaglutide SC once-daily / Novo Nordisk - LARVOL DELTA

Proteomic signatures reflect effects of semaglutide treatment for MASH. (PubMed, JHEP Rep) - P2, P3 | "In addition, participants with biopsy-confirmed MASH from the phase IIb Sema-MASH trial who received once-daily semaglutide or placebo for 72 weeks were included. SomaSignal is a proteomics-based model designed to non-invasively test for and validate MASH components as well as detect the prevalence of metabolic dysfunction-associated steatotic liver disease stages, against biopsy results. In the future, SomaSignal MASH components may have an impact on future clinical practice by providing clinicians with an alternative option for non-invasive assessment of treatment effects in the early clinical stages of therapeutic development."

Clinical • Journal • Diabetes • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Efficacy and safety of once-daily oral semaglutide in patients with heart failure with preserved ejection fraction, type 2 diabetes and obesity: a real-world study. (PubMed, Eur J Intern Med) - "Once-daily oral semaglutide was associated with an improvement in heart failure health status, and weight loss in patients with heart failure with preserved ejection fraction, type 2 diabetes, and obesity. Further research on glucagon-like peptide-1 receptor agonists in heart failure with preserved ejection fraction is needed."

Journal • Real-world evidence • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

SAFETY PROFILE OF SEMAGLUTIDE IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS: POST-HOC ANALYSIS OF DATA FROM TWO PHASE 2 STUDIES (UEGW 2024) - P2, P3 | "Aims & This was a post-hoc analysis of two trials: NCT02970942 (320 patients with fibrosis stage F1–3 randomised 3:1 to once-daily semaglutide 0.1, 0.2 or 0.4 mg [n=80, 78 and 82] or placebo [n=80] for 72 weeks) and NCT03987451 (71 patients with compensated cirrhosis randomised 2:1 to once-weekly semaglutide 2.4 mg [n=47] or placebo [n=24] for 48 weeks)... Data from two phase 2 trials indicate that semaglutide is generally well tolerated in patients with MASH, including those with compensated cirrhosis. No new safety concerns were identified, and the safety profile was similar to that in patients with T2D and overweight/obesity. Data from the ongoing phase 3 trial (NCT04822181) will provide further knowledge about the safety of semaglutide in patients with MASH."

Clinical • P2 data • Retrospective data • Breast Cancer • Diabetes • Endometrial Adenocarcinoma • Endometrial Cancer • Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Hematological Malignancies • Hepatology • Immunology • Liver Failure • Lymphoma • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Oncology • Pancreatitis • Peripheral T-cell Lymphoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Type 2 Diabetes Mellitus

Novo Nordisk will stop the once-weekly injectable semaglutide kidney outcomes trial, FLOW, based on interim analysis (Novo Nordisk Press Release) - "Novo Nordisk today announced the decision to stop the kidney outcomes trial FLOW (Effect of semaglutide versus placebo on the progression of renal impairment in people with type 2 diabetes and chronic kidney disease). The decision to stop the trial is based on a recommendation from the independent Data Monitoring Committee (DMC) concluding that the results from an interim analysis met certain pre-specified criteria for stopping the trial early for efficacy....Novo Nordisk expects that FLOW will read out during the first half year of 2024."

P3 data • Trial completion • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Oral Semaglutide in Type 2 Diabetes Mellitus: a systematic review and meta-analysis. (PubMed, Diabetes Res Clin Pract) - "Once-daily semaglutide 7 and 14 mg can significantly lowered HbA1c and body weight in patients with T2DM, and this effect increases with dose. Significantly, more gastrointestinal events occurred with semaglutide 14 mg."

Journal • Retrospective data • Review • Diabetes • Gastrointestinal Disorder • Metabolic Disorders • Type 2 Diabetes Mellitus

NASH and pericarditis: VCU Wright Center researchers co-author two NEJM articles - "The research was presented at a recent virtual conference of the American Association for the Study of Liver Diseases, where Sanyal also presented a field overview of the NASH landscape and recent clinical trial results. Sanyal leads and is part of multiple research projects on NASH at VCU, some showing promise for the treatment of the disease, which is the leading cause for liver transplantation in the U.S."

Semaglutide (NASH-TAG 2021) - No abstract available

[VIRTUAL] SAFETY AND EFFICACY OF COMBINATION THERAPIES INCLUDING SEMAGLUTIDE, CILOFEXOR, AND FIRSOCOSTAT IN PATIENTS WITH NASH (AASLD 2020) - "In patients with NASH, combinations of sema with CILO and/or FIR were well tolerated and may provide additional benefits vs sema monotherapy."

Clinical • Combination therapy • Late-breaking abstract • Dermatology • Diabetes • Gastrointestinal Disorder • Hepatology • Metabolic Disorders • Non-alcoholic Steatohepatitis • Pruritus • MRI

TREATMENT WITH RESMETIROM IN PHASE 3 MAESTRO-NAFLD-1 NASH STUDY OPEN LABEL ARM: EFFECTS ON BIOMARKERS AND IMAGING (NASH-TAG 2021) - P3 | "Animals with biopsy-confirmed steatosis (score ≥2) and fibrosis (stage ≥1) received ALT-801 (10 nmol/kg; SC), semaglutide, a GLP-1 agonist (10 nmol/ kg; SC), elafibranor, a PPARα/δ agonist (78μmol/kg; PO) or vehicle (PO/SC) for 12 weeks. In this 52 week Phase 3 open label study, NASH patients identified using non-invasive imaging and biomarkers were treated with resmetirom 100 mg and demonstrated rapid reduction in hepatic fat, biomarkers and atherogenic lipids after 12-16 weeks of treatment, potentially supporting use of non-invasive tests to monitor individual NASH patient response to resmetirom treatment."

Biomarker • Clinical • P3 data • Diabetes • Dyslipidemia • Fibrosis • Hepatology • Hypertension • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • APOB • COL1A1 • MRI

[VIRTUAL] EFFICACY AND SAFETY OF SUBCUTANEOUS SEMAGLUTIDE ONCE-DAILY VERSUS PLACEBO IN PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS (AASLD 2020) - P2 | "In pts with NASH and F2–F3 fibrosis, sema led to higher levels of NASH resolution without fibrosis worsening. Improvement in histological fibrosis was not significant, although fewer pts had fibrosis progression and biomarkers of fibrosis improved vs PBO. Sema also improved a broad range of metabolic parameters."

Clinical • Addiction (Opioid and Alcohol) • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity • Type 2 Diabetes Mellitus

[VIRTUAL] Faculty (ENDO 2021) - "In patients with type 2 diabetes and NASH, pioglitazone and GLP-1 receptor agonists (liraglutide and semaglutide) have been shown to significantly improve liver histology. This session focuses on available drugs that could potentially be useful for management of patients with NAFLD/NASH. Many new molecules targeting metabolic pathways, inflammation, or oxidative stress and fibrosis are being studied, and understanding of the complex pathophysiology of NASH provides a rationale in the future for using combination of drugs to treat this condition."

Cardiovascular • Diabetes • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus

[VIRTUAL] Meet the Professor (ENDO 2021) - "In patients with type 2 diabetes and NASH, pioglitazone and GLP-1 receptor agonists (liraglutide and semaglutide) have been shown to significantly improve liver histology. This session focuses on available drugs that could potentially be useful for management of patients with NAFLD/NASH. Many new molecules targeting metabolic pathways, inflammation, or oxidative stress and fibrosis are being studied, and understanding of the complex pathophysiology of NASH provides a rationale in the future for using combination of drugs to treat this condition."

Cardiovascular • Diabetes • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus

[VIRTUAL] The combination of elafibranor and semaglutide drastically improves fibrosing steatohepatitis and distinctly modulates liver inflammatory signature (EASL-ILC-I 2020) - "Combination of low doses of elafibranor and semaglutide alleviates severe NASH phenotype and liver injury markers in AMLN diet-induced disease model. Transcriptomic studies reveal that ELA and SEMA synergize to specifically reduce the inflammatory infiltration in the liver."

Diabetes • Fibrosis • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

The effects of Glucagon-like Peptide-1 receptor agonists on kidney function and safety in type 2 diabetes. (PubMed, J Diabetes Investig) - "Currently, there are five GLP-1RAs (exenatide, lixisenatide, liraglutide, dulaglutide, and semaglutide) approved in Europe and USA...Most of these trials have the data of secondary exploratory renal endpoints, and the secondary renal outcomes from GLP-1RA CV outcome trials suggest a renal protective effect of GLP-1RA1. Based on the results of the previous trials, GLP-1RAs have been recommended in DKD patients if they are contraindicated or not tolerated to SGLT2 inhibitors."

Clinical • Journal • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Obesity therapeutics: The end of the beginning. (PubMed, Cell Metab) - "Obese non-diabetic patients receiving semaglutide, an injectable long-acting GLP-1 receptor agonist, in a large randomized placebo-controlled trial, lost and maintained ∼15% of their body weight for over a year (Wilding et al., 2021). This impressive result is likely to usher in a new era of anti-obesity drugs based on hormones that suppress food intake, largely through acting on the brain."

Journal • Genetic Disorders • Metabolic Disorders • Obesity

Semaglutide, a newly available glucagon-like peptide receptor agonist, shows remarkable favorable effects in hemodialysis patients with obesity and type 2 diabetes. (PubMed, Ther Apher Dial) - No abstract available

Clinical • Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

[VIRTUAL] Preclinical Weight Loss Efficacy of AM833 in Combination With Semaglutide in Rodent Models of Obesity (ENDO 2021) - "For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021."

Combination therapy • Preclinical • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

[VIRTUAL] Efficacy of Semaglutide by Background Sodium – Glucose Co-Transporter-2 Inhibitor: a Post Hoc Analysis of SUSTAIN 9 (DDG 2021) - "SUSTAIN 9 investigated semaglutide 1.0 mg vs placebo as add-on to a stable dose of sodium-glucose co transporter-2 inhibitor (SGLT-2i) therapy, with or without metformin or a sulfonylurea...In this post hoc analysis, SUSTAIN 9 data were analyzed by background SGLT-2i (empagliflozin, canagliflozin, dapagliflozin or other [ipragliflozin, luseogliflozin and tofogliflozin; drugs available only in Japan])...In conclusion, in subjects with T2D already receiving an SGLT-2i, semaglutide generally resulted in superior HbA1c and body weight reductions vs placebo, regardless of background SGLT-2i therapy. Joachim Kienhöfer is just presenting on behalf of the author group (Sponsored by Novo Nordisk A / S)."

Clinical • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

[VIRTUAL] Safety and Tolerability of Concomitant Administration of Multiple-Dose AM833 With Semaglutide 2.4 MG for Weight Management (ENDO 2021) - "Treatment with AM833 at all tested doses + semaglutide was generally well tolerated with an acceptable safety profile. PK data support once-weekly dosing. The combination of AM833 1.2, 2.4, or 4.5 mg + semaglutide led to greater weight loss compared with placebo + semaglutide."

Clinical • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Obesity

[VIRTUAL] Impact of Semaglutide on Body Composition in Adults With Overweight or Obesity: Exploratory Analysis of the STEP 1 Study (ENDO 2021) - "In adults with overweight/obesity, semaglutide 2.4 mg was associated with reduced total fat mass and regional visceral fat mass, and an increased proportion of lean body mass. Greater weight loss was associated with greater improvement in body composition (lean body mass:fat mass ratio). Unless otherwise noted, all poster abstracts presented at ENDO 2021 are embargoed until 11 AM Eastern on Saturday, March 20."

Clinical • Diabetes • Genetic Disorders • Obesity

[VIRTUAL] Efficacy and Safety of Semaglutide by Baseline BMI in SUSTAIN 1–5 and 7 (DDG 2021) - "Semaglutide had an acceptable safety profile in all BMI subgroups. Sebastian Pieperhoff will present this poster on behalf of the author group."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (clinicaltrials.gov) - P3; N=17500; Not yet recruiting; Sponsor: Novo Nordisk A/S

Clinical • New P3 trial • Cardiovascular • Genetic Disorders • Heart Failure • Obesity • CRP

Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (clinicaltrials.gov) - P3; N=17500; Recruiting; Sponsor: Novo Nordisk A/S; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cardiovascular • Genetic Disorders • Heart Failure • Obesity • CRP

[VIRTUAL] Mechanistic exploration of binding site of GLP-1 receptor and it’s small molecular agonist using in silico approaches (ACS-Sp 2021) - "In the present study, we attempt to design small molecular GLP-1 agonists that will play an identical role as the marketed Liraglutide or Semaglutide...Based on the analyses of the conformational changes, the receptor undergoes in both complexes sheds light on the cryptic binding site of small agonists and gives an insight into their probable mechanistic binding. This may lead to the solving of the unsolved mystery of small molecule GLP-1 agonists."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

[VIRTUAL] AM833, a Long Acting Amylin Analogue Induces Hypocalcemia in Young Rats via a Calcitonin Receptor Mediated Mechanism (ENDO 2021) - "When combined with the long acting GLP-1 analogue semaglutide for weight management, both preclinical studies in rat models of obesity and clinical trials in humans with obesity have demonstrated significant weight loss potential. The induction of hypercalcemia was a rodent specific phenomenon as no calcium lowering outside of normal range was seen in young dogs and rabbits. Clinical data confirmed that CTR induced calcium lowering was not human relevant, but these data showed that understanding physiology and pharmacology in the animal models of investigation as well as human translational relevance is of outmost importance in the progress of an early development program."

Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity