From the Guidelines
Retatrutide is not currently available as an oral medication for managing metabolic conditions such as type 2 diabetes, and metformin is typically the first-line oral therapy recommended. The management of type 2 diabetes often includes lifestyle modification and pharmacologic therapy, with several unique classes of drugs approved by the FDA to treat hyperglycemia, varying in cost and harms 1.
Current Recommendations for Type 2 Diabetes Management
- Metformin is usually recommended initially at 500mg once or twice daily, gradually increasing to an effective dose (typically 1000-2000mg daily in divided doses) 1.
- For patients needing additional glycemic control, oral SGLT-2 inhibitors or DPP-4 inhibitors are often added as second-line agents.
- Injectable GLP-1 receptor agonists like semaglutide or dulaglutide are highly effective for both glucose control and weight management but are not available in oral form except for Rybelsus (oral semaglutide) 1.
Key Considerations
- The choice of therapy should consider the individual's specific needs, including the presence of comorbidities, cost, and potential side effects.
- Lifestyle modifications are an essential part of managing type 2 diabetes, alongside pharmacologic therapy.
- The goal of treatment is to achieve and maintain individualized glycemic goals, reduce the risk of microvascular and macrovascular complications, and improve quality of life.
Given the most recent and highest quality evidence from 2025 1, the focus remains on metformin as the first-line treatment for type 2 diabetes due to its efficacy, safety, and cost-effectiveness, with other agents considered based on individual patient factors and response to initial therapy.
From the Research
Use of Retatrutide in Managing Metabolic Conditions
- Retatrutide is a novel triple agonist that targets the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon, showing promise in the treatment of obesity and type 2 diabetes 2, 3, 4, 5, 6.
- The primary end point in several phase 2 clinical trials was the percentage change in body weight from baseline to 24 weeks, with results ranging from -7.2% to -18% as the dose of retatrutide increased from 1 mg to 12 mg 2, 5.
Efficacy of Retatrutide
- Retatrutide has shown clinically meaningful improvements in glycaemic control and robust reductions in bodyweight, with a safety profile consistent with GLP-1 receptor agonists and GIP and GLP-1 receptor agonists 3.
- In people with type 2 diabetes, retatrutide demonstrated significant reductions in HbA1c and body weight, with least-squares mean changes from baseline in HbA1c ranging from -0.43% to -2.02% and body weight reductions ranging from 3.19% to 16.94% 3.
- A systematic review and meta-analysis of randomized controlled trials found that retatrutide significantly reduced body weight, body mass index, waist circumference, fasting plasma glucose, hemoglobin A1c, and systolic and diastolic blood pressure, with no significant difference in adverse events between the groups 6.
Safety Profile of Retatrutide
- The most common adverse events in the retatrutide groups were gastrointestinal, including nausea, diarrhea, vomiting, and constipation, which were dose-related and mostly mild to moderate in severity 3, 5.
- Dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter, with no reports of severe hypoglycemia and no deaths during the study 3, 5.
- The safety profile of retatrutide is consistent with GLP-1 receptor agonists and GIP and GLP-1 receptor agonists, with additional large and long-term trials required to establish these results 6.