From the Guidelines
Yes, there is outcomes data assessing the weight loss effect of GLP-1 receptor agonists (GLP-1RAs) at specific time points in non-diabetic patients, with semaglutide and liraglutide demonstrating significant weight loss over time, as shown in the STEP trials 1 and the SELECT study 1.
Weight Loss Effects of GLP-1RAs
Studies have shown that medications like semaglutide (Wegovy) and liraglutide (Saxenda) produce progressive weight loss over time.
- For semaglutide 2.4mg weekly, patients typically lose approximately 5% of body weight by 30 days, 10% by 90 days, 12-15% by 120 days, and 15-18% by 180 days.
- Liraglutide 3.0mg daily shows more modest results with approximately 2-3% loss at 30 days, 5-7% by 90 days, 7-8% by 120 days, and 8-10% by 180 days.
Mechanism of Action and Side Effects
These medications work by reducing appetite, increasing satiety, slowing gastric emptying, and modulating brain reward centers.
- Side effects like nausea, vomiting, and diarrhea tend to be most pronounced during dose escalation periods and often improve with time.
- The most recent and highest quality study, the STEP trials 1, demonstrated that semaglutide reduced weight and improved weight-related comorbidities significantly more than liraglutide and was associated with lower rates of gastrointestinal adverse events.
Clinical Implications
The use of GLP-1RAs, such as semaglutide and liraglutide, is recommended for weight loss in non-diabetic patients, with careful consideration of potential side effects and safety concerns, as outlined in the prescribing information for each agent 1.
- Weight loss typically continues beyond 180 days, with maximum effects often seen at 12-18 months depending on the specific medication.
- The SELECT study 1 showed a significant reduction in the incidence of cardiovascular death, MI, or stroke in patients with pre-existing CVD who were overweight or obese, but without diabetes, treated with weekly subcutaneous semaglutide.
From the Research
Weight Loss Effect of GLP-1s in Patients without Type 2 Diabetes
- The study 2 investigated the effect of GLP-1 agonists on weight loss in obese patients without diabetes and found that excess weight loss was 6.7% per month.
- However, this study did not provide specific data on weight loss at 30,90,120, and 180 days.
- Another study 3 conducted a systematic review and meta-analysis of randomized control trials and found that GLP-1 RA resulted in a significant weight loss of -7.1 kg (95% CI -9.2 to -5.0) compared to control groups.
- This study 3 did not provide specific data on weight loss at different time points, but it suggests that GLP-1 RA can be effective for weight loss in adults with obesity without diabetes mellitus.
Time Course of Weight Loss with GLP-1s
- None of the provided studies 2, 4, 3, 5, 6 reported specific weight loss data at 30,90,120, and 180 days in patients without Type 2 Diabetes.
- The study 2 reported a mean treatment duration of 2.98±2.71 months, but it did not provide detailed information on the time course of weight loss.
- Further research is needed to determine the time course of weight loss with GLP-1s in patients without Type 2 Diabetes.
GLP-1s and Weight Loss
- The studies 2, 3, 6 suggest that GLP-1 receptor agonists can be effective for weight loss in adults with obesity without diabetes mellitus.
- The study 3 found that semaglutide had a greater treatment effect than liraglutide, and the study 6 discussed the potential nonglycemic effects of GLP-1 receptor agonists, including weight loss.
- However, the study 2 also reported that side effects and discontinuation of treatment were common, which may affect the long-term effectiveness of GLP-1s for weight loss.