Fu Laimei (polyethylene glycol loxenatide) / Jiangsu Hansoh Pharma - LARVOL DELTA

A randomized, open-label, parallel, conventionally controlled clinical study to evaluate the metabolic effects of polyethylene glycol loxenatide in combination with whey protein therapy in patients with obesity (ChiCTR) - P4 | N=100 | Completed | Sponsor: The First Affiliated Hospital of Nanjing Medical University; The First Affiliated Hospital of Nanjing Medical University

New P4 trial • Genetic Disorders • Obesity

Efficacy of Polyethylene Glycol Loxenatide in Combination with Basal Insulin in Patients with Type 2 Diabetes Mellitus: A Retrospective Real-World Study. (PubMed, Diabetes Ther) - P=N/A | "PEG-Loxe + basal insulin combined therapy was safe and effective in patients with T2DM who did not achieve optimal glycemic control with insulin therapy alone."

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

Polyethylene Glycol Loxenatide Accelerates Diabetic Wound Healing by Downregulating Systemic Inflammation and Improving Endothelial Progenitor Cell Functions. (PubMed, Int J Mol Sci) - "In vitro, PEG-loxe restored EPC function by enhancing NO production, reducing mitochondrial ROS, improving cellular respiratory function, and restoring autophagic flux. These findings suggest that PEG-loxe offers therapeutic benefits for diabetic wound healing by downregulating systemic inflammation, enhancing angiogenesis, and improving mitochondrial quality control in EPCs, highlighting GLP-1RAs as potential therapies for diabetic vascular complications."

Journal • Cardiovascular • Diabetes • Inflammation • Metabolic Disorders • CXCL12 • HIF1A • IL5 • NOS3

Loxenatide Plus LNG-IUS in Endometrial Atypical Hyperplasia (clinicaltrials.gov) - P2/3 | N=30 | Active, not recruiting | Sponsor: Fudan University | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Once-weekly glucagon-like peptide receptor agonist polyethylene glycol loxenatide protects against major adverse cardiovascular events in patients with type 2 diabetes: a multicenter ambispective cohort study (FLYING trial). (PubMed, MedComm (2020)) - "In the PEG-Loxe versus control cohorts, 21 (1.6%) versus 476 (4.3%) patients experienced nonfatal stroke (HR 0.63; p = 0.041), whereas 22 (1.7%) versus 545 (4.9%) experienced nonfatal myocardial infarction (HR 0.66; p = 0.058), and the incidence of cardiovascular death was 8 (0.6%) versus 240 (2.2%), respectively (HR 0.56; p = 0.118). We found a significantly lower incidence of first nonfatal myocardial infarction, nonfatal stroke, or cardiovascular deaths in the PEG-Loxe cohort than the control cohort."

Adverse events • Journal • Cardiovascular • Diabetes • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus

Polyethylene glycol loxenatide protects diabetic kidneys by inhibiting GRP78/PERK/eIF2α pathway, and improves cardiac injury by suppressing TLR4/NF-κB inflammatory pathway. (PubMed, BMC Cardiovasc Disord) - "We showed that PEG-Loxe could decrease renal stress response and improve renal injury in T2DM by inhibiting endoplasmic reticulum stress via the GRP78/PERK/eIF2α pathway. Additionally, PEG-Loxe could hinder the TLR4/NF-κB inflammatory pathway and myocardial apoptosis and boost cardiac function, thus exerting protective effects on the cardiovascular system in T2DM."

Journal • Cardiovascular • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus • ATF4 • HSPA5 • MYD88 • TLR4

Polyethylene glycol loxenatide modulates lipid metabolism and insulin resistance through lncRNA steroid receptor RNA activator/cellular nucleic acid binding protein/Rho-associated coiled-coil kinase 2 axis in type 2 diabetes mellitus. (PubMed, J Diabetes Investig) - "High-PEG-Loxe relieves insulin resistance and lipid metabolism disorder in type 2 diabetes mellitus through SRA/CNBP/ROCK2 axis. This research provides a molecular mechanism of PEG-Loxe for treating type 2 diabetes mellitus."

Journal • Diabetes • Dyslipidemia • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • LEP • LIPI • RHOA

Warfarin pharmacokinetics and pharmacodynamics are not affected by concomitant administration of the long-acting GLP-1 receptor agonist polyethylene glycol loxenatide. (PubMed, Int J Clin Pharmacol Ther) - "Concomitant administration of PEX-168 and single-dose warfarin was well tolerated. PEX-168 had no effect on the pharmacokinetics or pharmacodynamics of warfarin."

Journal • PK/PD data

Effect of polyethylene glycol loxenatide treatment on body weight in patients with type 2 diabetes with different body mass index: a retrospective cohort study (ChiCTR) - P=N/A | N=200 | Not yet recruiting | Sponsor: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology; Tongji Hospital affiliated to Tongji Medical

New trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial. (PubMed, Front Endocrinol (Lausanne)) - "This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options. www.chictr.org.cn, identifier ChiCTR2300070919."

Clinical • Journal • Diabetes • Diabetic Nephropathy • Gastrointestinal Disorder • Glomerulonephritis • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Health Technology Assessment: Evaluation of 7 Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus. (PubMed, Risk Manag Healthc Policy) - "The final assessment result scores from highest to lowest were semaglutide (71.5 points), dulaglutide (68.9 points), liraglutide (68.7 points), exenatide (62.5 points), lixisenatide (59.9 points), polyethylene glycol loxenatide (55.9 points), and benaglutide (45.1 points). When a healthcare organization introduces GLP-1RAs to their hospital, they can refer to the assessment results and use the top three recommended medications: semaglutide, dulaglutide, and liraglutide."

Journal • Review • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Is polyethylene glycol loxenatide 100 μg the preferred glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus? A meta-analysis and trial sequential analysis. (PubMed, Eur Rev Med Pharmacol Sci) - "PEX168 100 μg can significantly lower blood glucose and does not increase the risk of total AEs, GI AEs, and hypoglycemia, which may be a preferred glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus."

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

Real-world effectiveness of GLP-1 receptor agonist-based treatment strategies on "time in range" in patients with type 2 diabetes. (PubMed, Front Pharmacol) - "Subgroup analysis revealed that, compared with the administration of liraglutide, the administration of semaglutide and polyethylene glycol loxenatide (PEG-Loxe) significantly improved TIR over 3-6 months of treatment (p < 0.05). These real-world findings indicate that GLP-1RA-based treatment strategies could be superior to oral treatment strategies for improving TIR among patients with T2DM and that once-weekly GLP-1RA may be more effective than a once-daily GLP-1RA. Clinical trial registration: http://www.chinadrugtrials.org.cn/index.html, identifier number ChiCTR2300073697."

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

Efficacy of polyethylene glycol loxenatide for type 2 diabetes mellitus patients: a systematic review and meta-analysis. (PubMed, Front Pharmacol) - "And the combination of conventional hypoglycemic drugs (CHD) and PEG-Loxe could more effectively improve the levels of HbA1c, FPG, 2-h PBG, TC, TG, BMI, and BW compared with CHD in T2DM patients. Systematic Review Registration: www.inplasy.com, identifier INPLASY202350106."

Journal • Retrospective data • Review • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Loxenatide Plus LNG-IUS in Endometrial Atypical Hyperplasia (clinicaltrials.gov) - P2/3 | N=28 | Recruiting | Sponsor: Fudan University | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial primary completion date • Genetic Disorders • Obesity

Efficacy Comparison of Polyethylene Glycol Loxenatide and Gliclazide on the Brain Function in T2DM Patients (clinicaltrials.gov) - P=N/A | N=58 | Recruiting | Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

New trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Role of Novel Glucagon-like Peptide-1 Receptor Analogue Polyethylene Glycol Loxenatide in Type 2 Diabetes: A Systematic Review and Meta-analysis. (PubMed, Indian J Endocrinol Metab) - "Occurrence of nausea [RR 16.85 (95% CI: 3.89 to 72.92); P < 0.01; I = 10%], vomiting [RR 15.90 (95% CI: 2.99 to 84.55); P < 0.01; I = 0%], and anorexia [RR 3.85 (95% CI: 1.24 to 11.88); P = 0.02; I = 0%] was significantly higher with high-dose peg-loxenatide, as compared to placebo. Peg-loxenatide (100 mcg/week) is the most appropriate dose for clinical use as it is associated with good glycaemic efficacy with minimal gastro-intestinal side effects."

Journal • Retrospective data • Review • Anorexia • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Clinical Efficacy of Polyethylene Glycol Loxenatide in the Treatment of Obese or Overweight Patients with Type 2 Diabetes Mellitus. (PubMed, J Coll Physicians Surg Pak) - "PEG Loxenatide considerably affects obese and overweight T2DM patients. With no noticeable adverse reactions, this drug is highly recommended for application and clinical promotion."

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

Efficacy and safety of polyethylene glycol loxenatide in type 2 diabetic patients: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Sci Rep) - "Polyethylene glycol loxenatide (PEX168) is a novel glucagon-like peptide-1 receptor agonist with a longer half-life developed by modifying the chemical structure of exenatide. PEX168 could be a viable option for treating diabetic patients whose metformin control is inadequate or who cannot tolerate metformin. PEX168 at 100 ug in combination with metformin was found to be safe and more effective compared to metformin; however, due to the small number of trials included, these findings should be interpreted with caution, and additional trials are required."

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

Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review. (PubMed, Front Endocrinol (Lausanne)) - "The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide...In addition, this study may provide reference and evidence-based medical evidence for clinicians to select GLP-1RAs in patients with T2D and high body mass index (BMI). Based on the NMA results, tirzepatide 15mg and semaglutide 1.0mg may be preferred."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparative efficacy and safety of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes: A network meta-analysis. (PubMed, Medicine (Baltimore)) - "Regimens of GLP-1RAs had differential glycemic control. The efficacy and safety of Semaglutide 2.0mg in comprehensively lowering blood sugar showed the best performance."

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

Efficacy of polyethylene glycol loxenatide versus insulin glargine on glycemic control in patients with type 2 diabetes: a randomized, open-label, parallel-group trial. (PubMed, Front Pharmacol) - "Objective: This trial aimed to evaluate the glycemic control of polyethylene glycol loxenatide measured with continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM), with the hypothesis that participants given PEG-Loxe would spend more time in time-in-range (TIR) than participants were given insulin glargine after 24 weeks of treatment. The SD of CGM glucose levels was 1.88 mmol/L for PEG-Loxe and 2.22 mmol/L for insulin glargine [ETD -0.34 mmol/L (95% CI: -0.55 to -0.12), p = 0.002], with a similar CV between the two groups. The addition of once-weekly GLP-1RA PEG-Loxe to metformin was superior to insulin glargine in improving glycemic control and glycemic variability evaluated by CGM in middle-aged and elderly patients with T2DM."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Impact of polyethylene glycol loxenatide on cardiovascular outcomes in patients with type 2 diabetes: study protocol for a multicentre, randomised, double-blind, placebo-controlled trial (BALANCE-3). (PubMed, BMJ Open) - "Polyethylene glycol loxenatide (PEG-Loxe) is a once-weekly GLP-1RA obtained by modifying exendin-4. The findings of this study will be published in a peer-reviewed journal. ChiCTR2200056410."

Journal • Cardiovascular • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Myocardial Infarction • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Short-term effect of polyethylene glycol loxenatide on weight loss in overweight or obese patients with type 2 diabetes: An open-label, parallel-arm, randomized, metformin-controlled trial. (PubMed, Front Endocrinol (Lausanne)) - "Additional trials are necessary to establish whether these effects can be maintained in the long term. www.chictr.org.cn, identifier ChiCTR2200057800."

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

Long-Term Cost-Effectiveness of Subcutaneous Once-Weekly Semaglutide Versus Polyethylene Glycol Loxenatide for Treatment of Type 2 Diabetes Mellitus in China. (PubMed, Diabetes Ther) - "From the perspective of Chinese healthcare systems, treatment with once-weekly subcutaneous semaglutide represents a dominant option versus PEG-loxenatide for patients with type 2 diabetes uncontrolled on metformin."

HEOR • Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus