Survodutide 10mg

Introduction to Survodutide

Survodutide (BI 456906) is an investigational synthetic peptide developed by Boehringer Ingelheim and Zealand Pharma as a dual agonist of the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R). It is designed to address obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatohepatitis (MASH) by combining the appetite-suppressing effects of GLP-1 receptor agonism with the energy-expenditure-enhancing effects of glucagon receptor agonism. Administered via once-weekly subcutaneous injections, Survodutide is currently in phase 3 clinical trials (SYNCHRONIZE-1, SYNCHRONIZE-2, and SYNCHRONIZE-CVOT) for obesity and T2D, and phase 2 trials for MASH-related cirrhosis.

Survodutide has shown promising results in phase 2 trials, achieving up to 18.7% body weight loss at 46 weeks with a 4.8 mg dose in adults with overweight or obesity (BMI ≥27 kg/m²) without T2D, and up to 1.7% HbA1c reduction in T2D patients after 16 weeks. While a 10mg dose is not explicitly documented in available trials, higher doses (up to 6.0 mg) have been tested, and this analysis assumes a 10mg dose would align with the observed dose-response trends for efficacy and safety. Survodutide is not yet approved by regulatory bodies like the FDA or EMA, and its use is restricted to clinical research settings due to ongoing evaluations of long-term safety and efficacy.

How Survodutide Works

Survodutide’s dual agonism targets two key receptors:

1. GLP-1 Receptor Agonism: GLP-1 receptor activation enhances insulin secretion in a glucose-dependent manner, suppresses glucagon release, slows gastric emptying, and reduces appetite by acting on hypothalamic centers. This leads to reduced caloric intake and improved glycemic control, particularly beneficial in T2D and obesity.

2. Glucagon Receptor Agonism: Glucagon receptor activation increases energy expenditure by stimulating hepatic glycogenolysis, gluconeogenesis, and lipolysis. This enhances fat oxidation and reduces liver fat content, making it particularly relevant for MASH and obesity management.

The synergistic effect of these mechanisms results in significant weight loss, improved metabolic parameters, and potential liver health benefits. In phase 2 trials, Survodutide (0.6–4.8 mg weekly) demonstrated dose-dependent reductions in body weight (up to 18.7% at 4.8 mg) and HbA1c (up to 1.7% at 1.8 mg twice weekly) over 46 and 16 weeks, respectively. Pharmacokinetic studies show that Survodutide’s half-life supports weekly dosing, with no significant alterations in pharmacokinetics in patients with cirrhosis, indicating no need for dose adjustments in hepatic impairment.

The drug’s tolerability profile is similar to GLP-1 receptor agonists, with gastrointestinal adverse events (nausea, vomiting, diarrhea) being the most common, particularly during dose escalation. These effects may be mitigated by slower dose up-titration, as observed in trials extending escalation periods.

Benefits of Using Survodutide

Survodutide’s potential benefits, based on phase 2 trial data and extrapolated to a hypothetical 10mg dose, include:

• Significant Weight Loss: In phase 2 trials, Survodutide 4.8 mg achieved up to 18.7% body weight reduction at 46 weeks in adults with BMI ≥27 kg/m² without T2D, with 54.7% of participants losing ≥15% of body weight. A 10mg dose could potentially yield greater reductions, as weight loss did not plateau at 4.8 mg, suggesting further efficacy at higher doses.

• Improved Glycemic Control: In T2D patients, Survodutide (up to 2.7 mg weekly or 1.8 mg twice weekly) reduced HbA1c by 1.5–1.7% after 16 weeks, comparable to semaglutide 1.0 mg. A 10mg dose may enhance glycemic control, particularly in longer-term studies.

• Cardiometabolic Health Benefits: Survodutide reduced systolic blood pressure (SBP) by 8.6 mmHg and diastolic blood pressure (DBP) by 4.8 mmHg at 4.8 mg, and waist circumference by up to 12.1 cm, indicating potential cardiovascular risk reduction.

• Liver Health Improvement: In MASH and cirrhosis patients, Survodutide reduced liver fat content, liver stiffness, and fibrosis biomarkers (e.g., Pro-C3, ELF score), suggesting therapeutic potential for MASH-related liver disease.

• Enhanced Energy Expenditure: Glucagon receptor agonism increases fat oxidation and energy expenditure, complementing GLP-1’s appetite suppression for a dual approach to obesity management.

• Tolerability in Cirrhosis: Survodutide’s pharmacokinetics remain consistent in patients with compensated or decompensated cirrhosis, supporting its use in MASH-related cirrhosis without dose adjustment.

Limitations include gastrointestinal side effects (75% of participants in phase 2 trials), high discontinuation rates (24.6% at 4.8 mg), and a lack of long-term safety data. Concerns about increased heart rate (2.7 beats per minute at 4.8 mg) and potential mitogenic risks from glucagon agonism require further investigation in phase 3 trials.

Certificate of Analysis

Survodutide 10mg – COA – FYP

The following technical details outline the properties of Survodutide 10mg, based on available data and assumptions for a 10mg dose.