From the Guidelines
Semaglutide is currently the most effective injectable GLP-1 agonist for weight loss, producing average weight loss of 14.9-16.0% when used at its full dose, as demonstrated in the STEP trials 1. The available injectable GLP-1 agonist drugs for weight loss include semaglutide and liraglutide. Key differences between these medications include:
- Efficacy: Semaglutide has been shown to produce greater weight loss compared to liraglutide, with mean weight loss at 68 weeks ranging from 14.9-16.0% for semaglutide versus 8.0% for liraglutide 1.
- Administration: Semaglutide is administered weekly, while liraglutide is administered daily.
- Side effects: Both medications share similar side effects, including nausea, vomiting, diarrhea, and constipation, which typically improve over time with gradual dose escalation 1.
- Serious but rare side effects: Both medications have been associated with serious but rare side effects, including pancreatitis, gallbladder disease, and thyroid C-cell tumors 1. The mechanism of action for these medications involves slowing gastric emptying, increasing satiety, and reducing hunger through GLP-1 receptor activation in the brain and gut. It is essential to note that these medications are most effective when combined with lifestyle modifications, including diet and exercise, as demonstrated in the STEP trials, where participants who received semaglutide and followed a reduced-calorie diet and participated in physical activity experienced greater weight loss compared to those who received placebo 1. Overall, semaglutide is the most effective injectable GLP-1 agonist for weight loss, but it is crucial to consider individual patient factors, including cost, availability, and potential side effects, when selecting a medication. Key points to consider when prescribing these medications include:
- Patient selection: Patients with obesity and related comorbidities may benefit from treatment with semaglutide or liraglutide.
- Dose escalation: Gradual dose escalation can help minimize side effects and improve tolerability.
- Lifestyle modifications: Combining medication with lifestyle modifications, including diet and exercise, can enhance weight loss and improve overall health outcomes.
- Monitoring: Regular monitoring of patients receiving these medications is essential to assess efficacy and potential side effects.
From the Research
Efficacy of Injectable GLP-1 Agonist Drugs for Weight Loss
- Semaglutide has demonstrated the largest weight loss of any obesity medication to date, with reductions of approximately 15% of initial weight at 68 weeks 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 found that dulaglutide reduced HbA1c more than liraglutide, and had similar effectiveness compared to exenatide once-weekly 4.
Side Effects of Injectable GLP-1 Agonist Drugs
- 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 Agonist Drugs
- Semaglutide has been shown to be more effective than liraglutide and dulaglutide in terms of weight loss, but tirzepatide may be more effective than semaglutide 3.
- Dulaglutide has been shown to be more effective than liraglutide in terms of reducing HbA1c, but had similar effectiveness compared to exenatide once-weekly 4.
- Switching from liraglutide or dulaglutide to semaglutide may be a useful treatment option for patients with metabolic abnormalities despite glucagon-like receptor-1 receptor agonist treatment 6.