GLP-1 Receptor Agonists Used in FLOW and SELECT Trials
Semaglutide was the GLP-1 receptor agonist used in both the FLOW and SELECT trials, with different dosages used in each study based on the target population.
FLOW Trial Details
- Drug: Semaglutide (injectable, once-weekly)
- Dosage: 1.0 mg subcutaneous injection weekly 1
- Population: Patients with type 2 diabetes and chronic kidney disease 2
- Primary Focus: Kidney outcomes in patients with CKD and T2D 3, 1
- Design: Randomized, double-blind, placebo-controlled trial 1
- Expected Completion: Late 2024 1
The FLOW trial is evaluating whether semaglutide can reduce kidney failure, persistent ≥50% reduction in eGFR, or death from kidney or cardiovascular causes in patients with type 2 diabetes and CKD 3, 1. This study is particularly significant as it will provide definitive evidence on renal outcomes with GLP-1 receptor agonists, which has been lacking despite promising secondary analyses from previous cardiovascular outcome trials 3.
SELECT Trial Details
- Drug: Semaglutide (injectable, once-weekly)
- Dosage: 2.4 mg subcutaneous injection weekly 3
- Population: Patients with pre-existing cardiovascular disease who were overweight or obese, but without diabetes 3
- Primary Focus: Cardiovascular outcomes (cardiovascular death, MI, or stroke) 3
- Results: Significant reduction in cardiovascular events (HR 0.80; 95% CI, 0.72–0.90) 3
The SELECT trial demonstrated that semaglutide at the higher 2.4 mg weekly dose significantly reduced the incidence of cardiovascular death, myocardial infarction, or stroke in patients with pre-existing cardiovascular disease who were overweight or obese but did not have diabetes 3.
Clinical Implications
Dosage Differences
- The higher dose (2.4 mg) used in SELECT was specifically for weight management in non-diabetic patients 4
- The lower dose (1.0 mg) used in FLOW is the standard dose for glycemic control in type 2 diabetes 1
Mechanism of Action
Semaglutide works by:
- Delaying gastric emptying
- Reducing hunger and food cravings
- Enhancing feelings of fullness after meals
- Acting on GLP-1 receptors in the hypothalamus 4
Cardiovascular and Renal Benefits
- Semaglutide has demonstrated cardiovascular benefits across multiple populations 5, 6
- In patients with heart failure with preserved ejection fraction (HFpEF), semaglutide reduced the risk of heart failure events (HR 0.59; 95% CI 0.41-0.82) 6
- In the FLOW trial, preliminary results show semaglutide increased time to first heart failure events or CV death (HR: 0.73; 95% CI: 0.62-0.87) 2
Important Considerations
- Semaglutide is contraindicated in pregnancy and should be used with caution in patients with history of pancreatitis or gallbladder disease 4
- Common adverse effects include gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation) 4
- For optimal results, treatment should be monitored monthly for the first 3 months and quarterly thereafter 4
- Early response (>5% weight loss after 3 months) predicts improved long-term outcomes 4
The use of semaglutide in these landmark trials highlights its expanding role beyond glycemic control to include cardiovascular and renal protection in diverse high-risk populations, with dosage tailored to the specific clinical context and treatment goals.