TIRZEPATIDE AND RETATRUTIDE IN THE TREATMENT OF OBESITY AND TYPE 2 DIABETES MELLITUS: CURRENT EVIDENCE AND FUTURE DIRECTIONS. A SYSTEMATIC REVIEW OF CURRENT LITERATURE

Rafał Bednarczyk; Natalia Bednarczyk; Radosław Krzysztof Binkowski; Agnieszka Kurek; Natalia Krajewska; Aleksandra Lejman; Aleksandra Mazurkiewicz; Hubert Sidor; Monika Wołosik; Szymon Zysiak

doi:10.31435/ijitss.1(49).2026.4671

Rafał Bednarczyk 10th Military Clinical Hospital with Independent Public Healthcare Centre Polyclinic in Bydgoszcz, Bydgoszcz, Poland https://orcid.org/0009-0002-0139-8586
Natalia Bednarczyk 10th Military Clinical Hospital with Independent Public Healthcare Centre Polyclinic in Bydgoszcz, Bydgoszcz, Poland https://orcid.org/0009-0003-2070-8559
Radosław Krzysztof Binkowski 4th Military Clinical Hospital with Polyclinic in Wroclaw, Wroclaw, Poland https://orcid.org/0009-0009-5925-1158
Agnieszka Kurek Military Institute of Medicine in Warsaw, Warsaw, Poland https://orcid.org/0009-0000-7906-213X
Natalia Krajewska Military Institute of Aviation Medicine in Warsaw, Warsaw, Poland https://orcid.org/0009-0001-0508-5790
Aleksandra Lejman 10th Military Clinical Hospital with Independent Public Healthcare Centre Polyclinic in Bydgoszcz, Bydgoszcz, Poland https://orcid.org/0009-0005-8637-2204
Aleksandra Mazurkiewicz 1st Military Clinical Hospital with Outpatient Clinic in Lublin, Lublin, Poland https://orcid.org/0009-0008-9074-3583
Hubert Sidor Military Institute of Medicine in Warsaw, Warsaw, Poland https://orcid.org/0009-0005-5432-9279
Monika Wołosik Military Institute of Medicine in Warsaw, Warsaw, Poland https://orcid.org/0009-0001-0129-4771
Szymon Zysiak Military Institute of Aviation Medicine in Warsaw, Warsaw, Poland https://orcid.org/0009-0002-8803-5736

DOI: https://doi.org/10.31435/ijitss.1(49).2026.4671

Keywords: Tirzepatide, Retatrutide, GLP-1 Receptor Agonist, GIP Receptor Agonist, Obesity Pharmacotherapy, Type 2 Diabetes Mellitus, Incretin-Based Therapy

Abstract

Background: The global prevalence of obesity and type 2 diabetes mellitus (T2DM) has achieved unprecedented levels, imposing substantial burdens on healthcare systems worldwide. Incretin-based pharmacotherapies have fundamentally transformed therapeutic approaches to these metabolic disorders over the past decade. Tirzepatide is a dual GIP/GLP-1 receptor agonist. Retatrutide additionally targets glucagon receptors. Both agents represent groundbreaking advances in metabolic pharmacotherapy.

Objective: This comprehensive review synthesizes clinical evidence from trials conducted between 2014 and 2024, examining pharmacological mechanisms, therapeutic efficacy, safety characteristics, and prospective clinical applications of these novel multi-receptor agonists.

Methods: We performed systematic literature searches across PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov databases. Selection criteria encompassed randomized controlled trials, systematic reviews, meta-analyses, and prospective cohort studies, adhering to PRISMA methodology throughout.

Results: Phase 3 clinical trials showed superior efficacy of tirzepatide compared to existing pharmacotherapies, reaching body weight reductions of approximately 22.5% and hemoglobin A1c (HbA1c) reductions of up to 2.4 percentage points. Phase 2 trials of retatrutide revealed even more remarkable outcomes, with weight reductions approaching 24.2% over 48 weeks. Both medications exhibited favorable cardiovascular profiles, though gastrointestinal adverse events constitute the predominant tolerability concern.

Conclusions: These pharmacological agents represent paradigm-shifting developments in obesity and diabetes management. Their therapeutic effectiveness approximates outcomes previously achievable only through surgical intervention, marking a transformative milestone for pharmacotherapy. Ongoing phase 3 trials will further elucidate their optimal positioning within clinical treatment algorithms.

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TIRZEPATIDE AND RETATRUTIDE IN THE TREATMENT OF OBESITY AND TYPE 2 DIABETES MELLITUS: CURRENT EVIDENCE AND FUTURE DIRECTIONS. A SYSTEMATIC REVIEW OF CURRENT LITERATURE

Abstract

References

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