Research
Hormonal
Discontinuation of FDA-approved GLP-1/GIP agonists (tirzepatide, semaglutide) does not lead to significant weight regain at the population level, contrasting with off-label drugs like phentermine and zonisamide which cause substantial regain.
If you stop taking tirzepatide or semaglutide, you are not guaranteed to regain all the weight immediately. Studies show that some weight loss benefit may persist for up to two years. This is different from older drugs like phentermine, where regain is common.
GoodSupportsHIGH confidence
In contrast, tirzepatide and semaglutide showed minor weight loss persisting up to two years post-discontinuation. Significant weight regain was consistently observed in both cohorts after discontinuing phentermine series, zonisamide, topiramate, and lisdexamfetamine.
Why this rating
Large cohort size and consistent findings across two datasets.
Source
Current status of anti-obesity medications and performance, an EHR based survey
Xiaoyang Ruan et al. · medRxiv · 2024
DOI 10.1101/2024.12.02.24318314
preprint · n=30519334Cited 3×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Long-term use of FDA-approved GLP-1/GIP agonists (tirzepatide and semaglutide) produces significant weight loss and metabolic improvements in real-world populations, though efficacy is lower than in randomized clinical trials due to conservative dosing and adherence issues.Good
- There is significant individual variability in response to all anti-obesity medications, with a substantial subset of patients experiencing weight gain or failing to achieve target weight loss, regardless of the drug class.Good
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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