European journal of internal medicineMar 15, 2026

Stopping incretin-based treatments in obesity: the challenges of ending therapy

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 17, 2026

Abstract

Discontinuation of incretin-based therapies may lead to weight regain of up to two-thirds of initial weight loss within one year.

Weight regain is often accompanied by early deterioration of cardiometabolic parameters.
Obesity is suggested to be a chronic, relapsing disease requiring long-term management.
Factors complicating the discontinuation of these therapies include neuroendocrine responses to weight loss and individual variability in treatment response.
There is a persistence of 'obesity memory' at the adipose tissue level after weight loss.
Emerging strategies to mitigate weight regain include dose de-escalation and lifestyle interventions, though robust evidence supporting these is currently lacking.
A shift towards a 'precision physician-patient relationship' may enhance individualized decision-making regarding treatment management.

Simplified

Incretin-based therapies, including mono-, dual-, and emerging triple-agonists, have transformed the pharmacological management of obesity by inducing substantial and sustained weight loss together with marked improvements in cardiometabolic risk factors. However, growing evidence from randomized withdrawal trials and meta-analyses demonstrates that discontinuation of these agents is consistently followed by rapid and clinically meaningful weight regain, often approaching two-thirds of the initial weight loss within one year, alongside early deterioration of cardiometabolic parameters. These observations reinforce the concept of obesity as a chronic, relapsing disease that generally requires long-term pharmacological management rather than time-limited treatment. This Opinion article examines the biological, clinical, and health-system factors that complicate discontinuation of incretin-based therapies, including adaptive neuroendocrine responses to weight loss, interindividual variability in treatment response, persistence of "obesity memory" at the adipose tissue level, and real-world challenges related to adherence, tolerability, and cost. We discuss emerging strategies aimed at mitigating post-withdrawal weight regain, such as dose de-escalation, low-dose maintenance, extended dosing intervals, and intensive lifestyle interventions, while highlighting the current lack of robust randomized evidence supporting these approaches. Finally, we propose reframing the concept of precision medicine in obesity toward a "precision physician-patient relationship," emphasizing individualized, longitudinal decision-making to guide treatment continuation, tapering, or discontinuation in the absence of reliable predictive biomarkers.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Declaration of competing interest AA received honoraria for speaker activities, for serving on advisory boards, or consultancy from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Amarin, Bruno Farmaceutici, Amgen, Novo Nordisk, and Sanofi. GPF received honoraria for speaker activities, for serving on advisory boards, or consultancy from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Guidotti, Novartis, Novo Nordisk, and Sanofi.

PubMed

Stopping incretin-based treatments in obesity: the challenges of ending therapy

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the glp-1 therapies brief