Both liraglutide and semaglutide are GLP-1 receptor agonists prescribed for medical weight loss, but semaglutide often demonstrates greater effectiveness at lower dosages. These medications are valuable for weight management in individuals with obesity or type 2 diabetes because they regulate hunger, slow gastric emptying, and improve blood sugar control.
Understanding GLP-1 Agonists
GLP-1 agonists, including liraglutide and semaglutide, promote weight loss by influencing appetite and digestion. These medications activate GLP-1 receptors in the brain, reducing hunger and increasing feelings of fullness after eating. They also slow down stomach emptying, preventing blood sugar spikes and promoting satiety with smaller meals. This combination of appetite suppression and improved blood sugar regulation can lead to consistent weight loss, especially when combined with lifestyle modifications. This can lead to significant reductions in body weight and improvements in related conditions like high blood pressure, high cholesterol, and type 2 diabetes.
How GLP-1 Medications Work
GLP-1 medications like liraglutide and semaglutide mimic the action of glucagon-like peptide-1 hormone. This hormone helps to reduce appetite and slow gastric emptying. By slowing the emptying of the stomach, these medications reduce hunger signals and enhance insulin sensitivity, which supports weight loss and helps manage conditions like type 2 diabetes.
Liraglutide and Semaglutide: Key Differences
While both liraglutide and semaglutide are effective in helping individuals achieve meaningful weight loss, they differ in dosing schedules and their specific effects on weight loss, with liraglutide requiring daily administration and semaglutide taken once a week. Individual responses to both medications may vary. Liraglutide and semaglutide are available under different brand names, which may influence dosages and patient responses.
Dosing and Administration
Liraglutide is administered daily, while semaglutide is given weekly. Semaglutide injection is given once weekly compared to once daily with liraglutide, a significant advantage for many people. The choice between more frequent dosing versus less frequent injections can play a role in the decision.
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- Liraglutide: Administered daily via subcutaneous injection.
- Semaglutide: Administered weekly via subcutaneous injection or available as an oral tablet (Rybelsus) taken once daily.
Efficacy in Weight Loss
In comparison, semaglutide, taken weekly, has demonstrated more significant weight loss, with studies showing an average decrease of over 12%. The differences in these medications lie primarily in their formulation as well as how the body responds to them over time. Semaglutide’s extended-release formulation leads to more sustained effects and greater overall weight reduction, making it a more effective option for those patients who have more significant quantities of weight they need to lose.
- Liraglutide: Clinical trials have reported around a 5-6% reduction in body weight. In STEP 1, liraglutide resulted in a weight loss of 5.4%.
- Semaglutide: Studies have shown an average decrease of over 12% in body weight. In the STEP 8 trial, adults with overweight or obesity without diabetes who received semaglutide achieved a mean body weight reduction of 15.8% vs 6.4% with liraglutide.
Brand Names and Indications
Liraglutide and semaglutide are marketed under various brand names:
- Liraglutide:
- Saxenda: Used for weight loss.
- Victoza: Used for managing type 2 diabetes.
- Semaglutide:
- Ozempic: Used for managing type 2 diabetes.
- Rybelsus: Oral tablet used for managing type 2 diabetes.
- Wegovy: Used for weight loss and to lower the risk of serious heart events in adults with obesity or overweight. It also received accelerated approval for the treatment of adults with metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver.
Cost Analysis
The cost needed to treat to achieve a 1% reduction in body weight using semaglutide or liraglutide was calculated. The total cost of therapy with liraglutide during the trial was estimated at $17,585 compared with $22,878 with semaglutide.
Clinical Trial Evidence
Semaglutide vs. Liraglutide in Clinical Trials
To date, no long-term phase III trials directly comparing semaglutide and liraglutide are available. However, a Bayesian framework and NMA were used for data synthesis. The data showed significant superiority in HbA1c reduction of semaglutide 1 mg QW over liraglutide 1.2 and 1.8 mg with a treatment difference of 0.47% and 0.3%, respectively. Semaglutide 0.5 mg QW was found to be significantly superior to liraglutide 1.2 mg in HbA1c reduction with a treatment difference of 0.17%. Regarding weight reduction analysis, semaglutide 0.5 and 1 mg QW were significantly associated with a greater reduction than liraglutide 0.6 mg with a treatment difference of 2.42 and 3.06 kg, respectively. Semaglutide improved the control of blood glucose and body weight. The capacity of long-term glycemic control and body weight control of semaglutide appears to be more effective than other GLP-1 RAs, including liraglutide.
SUSTAIN 10 Trial
The SUSTAIN 10 trial was a 30-week long, Phase 3b study in 577 adults with type 2 diabetes taking 1 to 3 oral antidiabetic drugs. In addition, the mean body weight decreased by 5.8 kg (12.8 lb) with semaglutide vs.
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STEP 8 Trial
In the STEP 8 trial, which compared once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both groups also received counseling for diet and physical activity), over 68 weeks, adults with overweight or obesity without diabetes who received semaglutide achieved a mean body weight reduction of 15.8% vs 6.4% with liraglutide.
Retrospective Cohort Study
Researchers performed a retrospective cohort study using data from the Cleveland Clinic electronic health record in Ohio and Florida from January 2015 through July 2023. Among the 3389 patients, the mean age was 50.4 years, and the median baseline body mass index (BMI) was 38.5 kg/m2. Most patients (54.7%) were women, and a majority (82.2%) had type 2 diabetes as the treatment indication. The racial composition was predominantly White (68.5%), followed by Black (20.3%) and Hispanic (7.0%). At 1 year, the mean percentage weight reduction was significantly greater with semaglutide (-5.1%) compared with liraglutide (-2.2%; P <.001). Of the total cohort, 40.7% maintained persistent medication coverage at 1 year, with higher persistence for semaglutide users (45.8%) compared with liraglutide users (35.6%).
Factors to Consider When Choosing Between Liraglutide and Semaglutide
When choosing between liraglutide and semaglutide for weight loss, patients should consider several factors:
- Dosing Schedules: Liraglutide is administered daily, while semaglutide is given weekly.
- Health Profile: Individuals with a history of certain health conditions or sensitivities to medication may respond differently to each drug.
- Potential Side Effects: Some studies have shown that semaglutide may be associated with higher rates of stomach side effects like nausea, diarrhea, and vomiting compared to liraglutide. Both medicines can lead to gastrointestinal side effects, which is a class side effects of GLP-1 agonists.
- Weight Loss Goals: Evaluate long-term weight loss goals and how either medication fits into an overall health and wellness plan.
- Medical History: The choice between liraglutide and semaglutide for weight loss often depends on factors such as the patient’s medical history, their tolerance to the medication, and their preference for daily versus weekly administration.
Potential Side Effects and Warnings
Stomach side effects are common with the GLP-1 agonist class, especially when first starting treatment or increasing your dose too quickly. Your doctor will start you on lower doses to help prevent side effects that may interrupt your treatment. Stomach side effects tend to subside over time and while your final maintenance dose is reached. In general, about 5% to 10% of people will need to stop treatment due to stomach side effects with GLP-1 agonists.
Access and Availability
Both tirzepatide and semaglutide are prescription medicines used with diet and exercise to treat people with type 2 diabetes or to help people lose and maintain weight loss.
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