Tirzepatide vs. Semaglutide: Weight Loss Duration
- Obesity is a multifactorial chronic disease caused by poor lifestyle habits, family history, concurrent medical conditions, or medications.1 Obesity can lead to different cardiovascular diseases such as hypertension,heart...
- The phase 3 SUSTAINX trial (NCT03558957) conducted by Rubino et al included 792 participants with obesity who were followed for 48 weeks after completing 20 weeks of once-weekly...
- The phase 3 SURMOUNT-4 trial (NCT04660643) conducted by Aronne et al included 670 participants with either overweight or obesity without diabetes who were followed for 52 weeks after...
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Introduction
Obesity is a multifactorial chronic disease caused by poor lifestyle habits, family history, concurrent medical conditions, or medications.1 Obesity can lead to different cardiovascular diseases such as hypertension,heart failure,coronary artery disease,and dyslipidemia. Treatment for obesity includes a wide range of options, both pharmacological and nonpharmacological. Some nonpharmacological options include a diet high in protein and fiber,caloric deficit,and increasing exercise.2 Pharmacological treatments include phentermine (lomaira; KVK Tech), orlistat (xenical; Roche), and naltrexone/bupropion (Contrave; Currax Pharmaceuticals). Newer medications, such as glucagon-like peptide-1 (GLP-1) agonists and GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, have shown efficacy in body weight reduction.3-5 Even though these medications have demonstrated efficacy in reducing body weight, there is less evidence evaluating weight regain after stopping GLP-1 or GLP-1/GIP agonists.
The phase 3 SURMOUNT-4 trial (NCT04660643) conducted by Aronne et al included 670 participants with either overweight or obesity without diabetes who were followed for 52 weeks after completing 36 weeks of a maximum-tolerated tirzepatide lead-in regimen. At week 36, participants had a mean weight loss of approximately 20.9%.8 Participants were then randomly assigned to 2 groups: 1 group continued once-weekly tirzepatide (n = 335), and the other group received placebo (n = 335). At week 88, the tirzepatide group lost an additional average of 5.5% in body weight, and the placebo group gained an average of 14% in body weight.8
The phase 3 STEP 1 trial (NCT03548935) conducted by Wilding et al followed participants for 68 weeks of once-weekly subcutaneous semaglutide or placebo. Upon completion of the study, there was an average weight loss of about 17.3% in the semaglutide group and 2% in the placebo group.9 The STEP 1 trial extension, conducted by Wilding et al, followed patients after the STEP 1 trial until week 120. At week 120, 52 weeks after semaglutide discontinuation, the original semaglutide group regained 11.6% and the original placebo group regained 1.9% of total weight loss.9
In a study conducted by Bartelt et al, researchers analyzed 20,274 patients over 1 year who completed semaglutide and lost at least 5 pounds. At month 3 after the discontinuation of semaglutide, 29% either lost additional weight or doubled their initial weight loss, 39% maintained their initial weight loss, and 32% had some weight regain or complete weight regain.10 At month 12 after stopping semaglutide,36% of patients either lost additional weight or doubled their initial weight loss,20% maintained their initial weight loss,and 44% had some weight regain or complete weight regain.10
Researchers also analyzed 17,733 patients over 1 year who completed liraglutide and lost at least 5 pounds. At month 3 after stopping liraglutide, 28% either lost additional weight or doubled their initial weight loss, 33% maintained their initial weight loss, and 32% had some weight regain or complete weight regain.10 At month 12, 35% of patients either lost additional weight or doubled their initial weight loss, 21% maintained their initial weight loss, and 45% had some weight regain or complete weight regain.10
These studies demonstrate that both weight loss and weight regain are seen with GLP-1 agonists; however, participants who received placebo also had some weight loss and weight regain, although to a lesser extent. This could show that there could be other factors contributing to weight regain after GLP-1 agonist discontinuation, such as environment, diet, exercise, or other lifestyle choices.
Clinical implications
These findings suggest that obesity should be treated as a chronic condition, even after weigh“`html
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overweight and obesity. National Heart,Lung,and Blood Institute.
Accessed July 14, 2025.
www.nhlbi.nih.gov/health/overweight-and-obesity
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Obesity treatment overview. johns Hopkins Medicine. Accessed July 14, 2025.
www.hopkinsmedicine.org/health/conditions-and-diseases/obesity/obesity-treatment-overview
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Kommu S, Whitfield P.Semaglutide.
Weight Regain Common After Stopping Obesity Drugs
Many people regain weight after discontinuing glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used for obesity,according to recent research. These medications, initially developed for type 2 diabetes, have become popular for weight loss, but maintaining that loss proves challenging for many.
A comprehensive review published in the Journal of Obesity in 2024 examined weight regain following GLP-1 RA discontinuation. Researchers found a meaningful portion of patients experienced weight increase after stopping the drugs.
- National Library of Medicine – StatPearls: Glucagon Like Peptide 1 Receptor Agonists
- Abdullah Bin Ahmed I. A comprehensive review on weight gain following discontinuation of glucagon-like peptide-1 receptor agonists for obesity. J Obes. 2024;2024:8056440. doi:10.1155/2024/8056440
The review highlights the importance of continued lifestyle interventions – diet and exercise – even after stopping medication. Long-term weight management frequently enough requires a multifaceted approach, and simply relying on drugs isn’t a enduring solution for everyone.
Further research is needed to determine the optimal strategies for minimizing weight regain after GLP-1 RA discontinuation, but current evidence suggests a proactive, holistic approach is crucial.