“Is weight loss sustained after stopping treatment with a GLP-1 receptor agonist? Will rapid weight gain occur?
Unfortunately, the weight loss benefit of GLP-1 receptor agonists does go away when you stop the medication. Patients can regain some or all of the weight they lose.
The STEP 4 withdrawal trial compared the effect on body weight of continuing once-weekly treatment with subcutaneous semaglutide (2.4 mg) vs switching to placebo (both with lifestyle intervention) in adults with overweight or obesity.
After a 20-week run-in period with a mean weight loss of 10.6%, participants who were randomized to continue semaglutide for 48 more weeks continued to lose weight (-7.9%), whereas those randomized to switch to placebo gradually regained 6.9% of the weight between Week 20 and Week 68.
These results are similar to results from the follow-up phase of the SCALE Maintenance trial of liraglutide vs placebo (both with lifestyle intervention), where participants lost weight during the 56-week treatment phase but then regained some weight during the 12-week post-drug discontinuation follow-up.
What do these semaglutide and liraglutide trial results tell us? They tell us that obesity is a chronic disease. We should look at obesity treatment the same way we look at hypertension or hyperlipidemia treatment. If you stop taking antihypertensive medications, your blood pressure will go up again; if you stop taking a GLP-1 receptor agonist, your weight will go up again.”
From:
What Can We Learn From GLP-1 Receptor Agonist Studies on Weight Loss?
Source: From ENDO 2021: Ushering in a New Era of Sustainable Weight Loss with Incretin-Based Therapies
Clinical Care Options, 2021
https://www.clinicaloptions.com/diabetes/programs/2021/obesityendo2021/clinicalthought/ct2/page-1
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial
JAMA, 2021
https://pubmed.ncbi.nlm.nih.gov/33755728/
“Regarding the controversy of whether GLP-1–based therapy can increase the risk for specific malignant disease like pancreatic carcinoma and thyroid cancer, our conclusion is that apparently there is neither firm evidence in favor of this hypothesis nor evidence strong enough to rule out any such increased risk based on results available at present. We may learn answers to some of the questions from ongoing randomized controlled trials (e.g., cardiovascular safety trials underway for most approved compounds within the classes of GLP-1 receptor agonists or DPP-4 inhibitors) by analyzing databases or registries better suited for an unbiased postmarketing surveillance of adverse events associated with novel antidiabetes drugs. However, as of today the evidence in favor of the hypothesis that incretin-based medications cause specific types of malignant disease (e.g., pancreatic or [medullary] thyroid cancer) or increase the risk for cancer in a more general sense is not convincing enough to be seriously considered when making treatment decisions regarding the choice of antidiabetes medications.”
From:
Do GLP-1–Based Therapies Increase Cancer Risk?
Diabetes Care, July 2013
“All GLP-1 receptor antagonists have been associated with thyroid cancer in rodents, and in fact carry a boxed warning about the potential for cancer in humans. This leads many clinicians to ask if they should be concerned about using these drugs in patients who have or develop specific types of thyroid cancer—this is a clinical dilemma since these drugs work well and discontinuing them creates risk of elevated glucose and the need to readjust treatment. A One Minute Consult in the March 2015 issue of Cleveland Clinic Journal of Medicine summarizes important facts succinctly:
There are 4 types of thyroid cancer: medullary, papillary, follicular, and anaplastic.
GLP-1 receptor agonists can be safely used in all patients with papillary and follicular thyroid cancers; these develop from the thyroid follicular epithelium.
GLP-1 receptor agonists are currently contraindicated in patients with medullary thyroid cancer (which is very rare in humans) and in patients with multiple endocrine neoplasia 2 (MEN-2). The latter is not thyroid cancer.
Exercise caution when using GLP-1 receptor agonists in patients with familial thyroid cancer or genetic predisposition to papillary or follicular thyroid cancer. These cancers express GLP-1 receptors.
Several other human tumors have express GLP-1 receptors, but animal studies have not linked GLP-1 receptor agonists to these cancers.
The authors conclude GLP-1 receptor agonists’ benefits in type 2 diabetes mellitus outweigh risks of medullary thyroid cancer, and except in patients who have or are at risk for this rare cancer, clinicians can prescribe them without worry.”
From:
GLP-1 Receptor Agonists and Thyroid Cancer: Differentiating Cancer Type
HCP Live, 2015
https://www.hcplive.com/view/glp-1-receptor-agonists-and-thyroid-cancer-differentiating-cancer-type
New Drug Tirzepatide Shows Extraordinary Results For Obesity and Type 2 Diabetes
Diatribe Learn, April 2022
https://diatribe.org/new-drug-tirzepatide-shows-extraordinary-results-obesity-and-type-2-diabetes
Many in weight loss forums use language like “This is just a tool.” The question is not whether or not Mounjaro (or WeGovy, another GLP-1RA that results in weight loss) is a tool. The question is “Is it a tool you must use long term, or a tool that can be used short-term to achieve long-term results?” So far, the research points to the former and not the latter.
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity
The STEP 4 Randomized Clinical Trial
JAMA, April 2021