Semaglutide vs Liraglutide vs Dulaglutide is a comparison of the three commonly used GLP-1 analogs. With the recent FDA approval of Semaglutide for weight loss, it is important for clinicians to know the efficacy of the three drugs in terms of their weight-losing effects.
The “Pioneer 4” and “Sustain 7” were the two important clinical trials that directly compared Semaglutide vs Liraglutide and Semaglutide vs Dulaglutide. However, it was the “STEPS Trials” that were the basis of FDA approval of Semaglutide for weight loss.
How GLP-1 analogs cause weight loss?
GLP-1 analogs are incretin-mimetic drugs. The two most common incretins in the human body are GLP (glucagon-like peptide) and GIP (gastric inhibitory peptide).
The first GLP-1 analog (Exanetide, Byetta) was extracted from the saliva of the GILA monster. Incretins were discovered when scientists observed that insulin secretion is greatest with oral glucose load compared to intravenous administration of insulin.
Insulin secretion is more when glucose is given orally vs IV
GLP-1 analogs cause the secretion of insulin and suppression of glucagon in a glucose-dependent mechanism. Thus, their effects are maximum when the plasma glucose levels are high.
GLP-1 analogs cause the inhibition of stomach motility and impair the absorption of nutrients. This effect directly results in appetite suppression since individuals feel bloated immediately after eating the first few boluses of their meal.
GLP-1 analogs delay gastric emptying
It also causes nausea and vomiting that aggravates the situation further. The first GLP-1 analog that was approved for the treatment of weight loss in both diabetic and non-diabetic individuals was Liraglutide (Victoza).
The appetite suppressive effects of liraglutide were also thought to be mediated via central mechanisms. Food in the stomach results in stomach stretch.
This activates the afferent neurons from the stomach resulting in direct suppression of the appetite center in the hypothalamus.
Weight loss effects of Semaglutide vs Liraglutide vs Dulaglutide:
Weight loss effects of Semaglutide (Wegovy):
In the STEP-1 Trial, Semaglutide was studied in a dose of 2.4 mg administered weekly. Individuals in the study were either obese with a BMI of 30 kg/m² or more or were overweight with a BMI of 27 kg/m or more with at least one weight-related condition like hypertension and high cholesterol levels.
With Semaglutide treatment, a weight loss of 14.9% was observed at the end of the trial (12.4% difference compared to placebo) [Ref].
In the STEP 2 Trial, Semaglutide resulted in a weight loss of 9.6% in obese diabetic patients [Ref].
In the STEP-3 Trial, when administered with intensive lifestyle modification and a low caloric diet, it resulted in a weight loss of 16% [Ref].
The STEP-4 trial evaluated whether maintenance treatment with Semaglutide can result in sustained weight loss or not.
It was found to induce a weight loss of 7.9% compared to placebo where a weight gain of 6.9% was observed [Ref].
Weight loss effects of Liraglutide (Saxenda, Victoza):
The weight loss effects of Liraglutide were studied in the SCALE Trials (Satiety and Clinical Adiposity – Liraglutide Evidence) in individuals with and without diabetes [Ref].
Liraglutide was compared with orlistat in patients with a BMI of 30 – 40 kg/m². Liraglutide resulted in a weight loss of 4.8 kgs, 5.5 kgs, 6.3 kgs, and 7.2 kgs when administered in a dose of 1.2 mg, 1.8 mg, 2.4 mg, and 3.0 mg respectively. Patients in the placebo group lost only 2.8 kgs.
Individuals who received 2.4 mg and 3.0 mg liraglutide had a greater weight loss compared to placebo (6.3 kgs, and 7.2 kgs, compared to 4.1 kgs in the placebo group).
Similarly, in the scale obesity and prediabetes trial, it resulted in a significant weight loss compared to placebo (8.0% vs 2.6%).
In the SCALE Diabetes Trial, when liraglutide was administered in a dose of 1.8 mg and 3.0 mg daily, it resulted in a weight loss of 5 kgs (4.7%) and 6.4 kgs (6.0%) respectively compared to 2.2 kgs (2%) in the placebo group.
In the SCALE Sleep Apnea trial, liraglutide administered in a dose of 3.0 mg resulted in a weight loss of 5.7% versus 1.6% in the placebo.
Rybelsus was compared with Liraglutide. The weight loss effects of both Rybelsus and Liraglutide were comparable as seen below:
Weight loss effects of Dulaglutide (Trulicity):
Dulaglutide exerts some weight-losing effects. In the AWARD-9 clinical trial, it resulted in a weight loss of 1.91 kgs (and a 2.41 kg difference compared to placebo, P<0.001).
A network meta-analysis of 34 studies evaluated taspoglutide, exenatide, and dulaglutide. The mean weight change was greatest with 20 mg of taspoglutide (1.3 kgs) followed by weekly exenatide and dulaglutide (0.8 kgs) [Ref].
Direct Weight loss Comparisons of Semaglutide vs Liraglutide vs Dulaglutide:
The Pioneer 4 Trial evaluated oral Semaglutide and subcutaneous Liraglutide vs placebo in diabetic patients in a randomized double-blinded trial.
At week 26 of the treatment, it was observed that oral Semaglutide and subcutaneous liraglutide had comparable efficacy in reducing the glycated hemoglobin, however, oral Semaglutide was superior to Liraglutide in reducing weight.
Participants in the oral Semaglutide group had a mean weight loss of 4.4 kgs compared to 3.1 kgs in the Liraglutide group and 0.5 kgs in the placebo group [Ref].
Here is a summary of the PIONEER 4 Trial:
Once-weekly Semaglutide vs Dulaglutide in Diabetic Patients:
The SUSTAIN-7 Trial evaluated the effects of once-weekly Semaglutide in a dose of 0.5 mg and 1 mg compared to once weekly Dulaglutide administered in a dose of 0.75 and 1.5 mg.
All patients in the trials were diabetic and on metformin monotherapy. Semaglutide administered in a dose of 0.5 mg weekly resulted in an HbA1C reduction of 1.5% compared to a 1.1% reduction in patients who received 0.75 mg dulaglutide once weekly.
The mean weight loss in participants who received 0.5 mg Semaglutide was 4.6 kgs vs 2.3 kgs in the 0.75 mg dulaglutide group.
HbA1C reduction in the participants who received 1 mg Semaglutide compared to 1.5 mg dulaglutide was 1.8% and 1.4% respectively.
Similarly, greater weight loss occurred in the 1 mg Semaglutide group compared to the 1.5 mg Dulaglutide group (6.5 kgs vs 3.0 kgs) [Ref]. Here is a summary of SUSTAIN 7 Trial results:
Oral Semaglutide and injectable Liraglutide have comparable antidiabetic efficacies, however, Oral Semaglutide is better in reducing body weight. Once-weekly Semaglutide is more effective in reducing weight compared to once-weekly Dulaglutide. It is also more effective in lowering glycated hemoglobin.
Keywords studied in the above article:
- Ozempic Vs Trulicity Vs Victoza (Ozempic Vs Trulicity Vs Saxenda)
- Ozempic Vs Trulicity (Trulicity Vs Ozempic)
- Ozempic Vs Victoza (Victoza Vs Ozempic, Saxenda Vs Ozempic)
- Semaglutide Vs Dulaglutide (Dulaglutide Vs Semaglutide)
- Semaglutide Vs Liraglutide (Liraglutide Vs Semaglutide)
- Rybelsus Vs Trulicity Vs Victoza (Rybelsus Vs Trulicity Vs Saxenda)
- Rybelsus Vs Liraglutide (Liraglutide Vs Ryebelsus)
- Rybelsus Vs Dulaglutide (Dulaglutide Vs Rybelsus)
- Wegovy Vs Liraglutide (Wegovy Vs Dulaglutide, Wegovy Vs Trulicity)
- Liraglutide Vs Wegovy (Victoza Vs Liraglutide, Saxenda Vs Liraglutide)