From the Guidelines
Semaglutide is the most effective injectable GLP-1 agonist for weight loss, producing an average weight loss of 14.9-16.0% at 68 weeks, as demonstrated in the STEP trials 1.
Efficacy Comparison
The efficacy of different injectable GLP-1 agonists varies, with semaglutide showing the most significant weight loss, followed by liraglutide, which achieved a mean weight loss of 8.0% at 56 weeks 1.
Side Effects Comparison
All injectable GLP-1 agonists share common side effects, including nausea, vomiting, diarrhea, and constipation, which typically improve over time 1.
- Semaglutide and liraglutide have been associated with gastrointestinal adverse effects, particularly nausea and vomiting, with an incidence of 40% and 16%, respectively, for liraglutide 1
- Rare but serious side effects across all options include pancreatitis, gallbladder disease, and potential thyroid tumors (based on animal studies) 1
Treatment Considerations
Treatment duration is typically long-term, as weight regain occurs when medication is discontinued 1.
- Gradual dose escalation is necessary to minimize side effects, with weekly injections (except daily liraglutide) improving convenience
- The balance between weight loss and adverse effects is favorable for using semaglutide and liraglutide, despite the potential for gastrointestinal adverse effects 1
From the Research
Efficacy of Injectable GLP-1 Agonists for Weight Loss
- Semaglutide has been shown to have superior efficacy in weight reduction compared to placebo and other antidiabetic medications, leading to FDA approval for weight loss 2.
- A systematic review and meta-analysis found that semaglutide had a greater mean weight loss compared to liraglutide and dulaglutide, but tirzepatide had a greater mean weight loss compared to semaglutide 3.
- The mean weight loss reductions for different GLP-1 agonists were:
- Semaglutide: 4.81 kg
- Liraglutide: 2.81 kg
- Dulaglutide: 4.03 kg
- Tirzepatide: 9.7 kg
- Exenatide: 1.9 kg 3
- A real-world study and meta-analysis found that dulaglutide reduced HbA1c more than liraglutide, and had similar effectiveness compared to exenatide once-weekly 4.
Side Effects of Injectable GLP-1 Agonists
- Common adverse events associated with GLP-1 agonists include minor and moderate gastrointestinal events, such as nausea, vomiting, and diarrhea 3, 5.
- GLP-1 receptor agonists are not associated with hypoglycemia, but may cause a relatively high frequency of gastrointestinal disturbances 5.
- A study found that switching from liraglutide or dulaglutide to semaglutide improved treatment satisfaction and reduced body weight, with minimal adverse events 6.
Comparison of Different GLP-1 Agonists
- Semaglutide has been compared to other GLP-1 agonists, including liraglutide, dulaglutide, and tirzepatide, and has been found to have varying degrees of efficacy and safety 3, 4, 6.
- Tirzepatide, a dual-agonist, has been found to have greater weight loss compared to semaglutide, but the paucity of comparative head-to-head trials prevents a definitive conclusion of the superiority of one GLP-1 agonist over another 3.