IS OBESITY PHARMACOTHERAPY A LIFETIME COMMITMENT? A STRUCTURED REVIEW OF WEIGHT REGAIN AND STRATEGIES FOLLOWING INCRETIN CESSATION

Kornelia Domagała; Amanda Dolores Abramowicz; Magdalena Rumin; Olga Tatarata; Maja Osuch; Maciej Osuch; Anna Kiełboń; Martyna Jaciubek; Carmena Luty; Zuzanna Olga Reklewska

doi:10.31435/ijitss.1(49).2026.5125

Authors

Kornelia Domagała 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0008-4148-9320
Amanda Dolores Abramowicz Military Institute of Aviation Medicine, Warsaw, Mazovia, Poland https://orcid.org/0009-0004-6674-0594
Magdalena Rumin Military Institute of Aviation Medicine, Warsaw, Mazovia, Poland https://orcid.org/0009-0009-4281-8971
Olga Tatarata Military Institute of Aviation Medicine, Warsaw, Mazovia, Poland https://orcid.org/0009-0007-1279-7394
Maja Osuch 4th Military Clinical Hospital with Polyclinic SPZOZ in Wrocław, Wrocław, Poland https://orcid.org/0009-0000-9815-2608
Maciej Osuch 4th Military Clinical Hospital with Polyclinic SPZOZ in Wrocław, Wrocław, Poland https://orcid.org/0009-0009-2399-2878
Anna Kiełboń Military Institute of Medicine in Warsaw, Warsaw, Mazovia, Poland https://orcid.org/0009-0004-9028-6395
Martyna Jaciubek Military Institute of Aviation Medicine, Warsaw, Mazovia, Poland https://orcid.org/0009-0002-5520-0002
Carmena Luty 118th Military Hospital with Polyclinic SPZOZ in Ełk, Ełk, Poland https://orcid.org/0009-0007-6084-0385
Zuzanna Olga Reklewska The Military Medical Training Center, Łódź, Poland https://orcid.org/0009-0008-3539-646X

DOI:

https://doi.org/10.31435/ijitss.1(49).2026.5125

Keywords:

Obesity, Incretin-Based Therapies, Weight Regain, Chronic Care, GLP-1 Receptor Agonists

Abstract

Background: The 2026 World Health Organization (WHO) guidelines formalize a major shift in metabolic medicine by characterizing obesity as a chronic, progressive, and relapsing neuroendocrine disease. While innovative incretin-based medical technologies - specifically GLP-1 and dual GIP/GLP-1 receptor agonists - have achieved weight-loss magnitudes previously reserved for invasive metabolic surgery, the long-term durability of these outcomes after treatment cessation remains a formidable socio-clinical challenge.

Objective: This structured narrative review synthesizes contemporary evidence regarding weight-loss maintenance, the biological drivers of regain, and the systemic barriers to treatment persistence following the discontinuation of incretin-based therapies.

Methods: A comprehensive search of major bibliographic databases (2011–2026) was conducted, integrating data from randomized withdrawal trials (STEP and SURMOUNT programs), large-scale meta-analyses, and diverse real-world evidence (RWE).

Results: Evidence indicates that statistically significant weight regain can emerge as early as 8 weeks post-discontinuation, with substantial recovery of lost weight typical within 12 months. This rebound is primarily mediated by a biological “energy gap” of approximately 120 kcal per kilogram lost, driven by a combination of adaptive thermogenesis (reduced energy expenditure) and heightened orexigenic signaling. Crucially, real-world data reveal a significant "persistence gap," with 50–67% of patients discontinuing therapy within the first year due to economic barriers, global supply instabilities, and tolerability issues.

Conclusions: Effective obesity management requires a transition from short-term interventions to a lifelong "chronic care continuum." Future strategies must prioritize the preservation of fat-free mass, implement intensified monitoring protocols (specifically the 25% regain threshold), and promote a systemic reframing of pharmacotherapy as a permanent metabolic stabilizer rather than a transient cure.

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