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Peer-reviewedCC BY 4.0Journal of Clinical Medicine

Practical Challenges of Switching and Cross-Titration Between Incretin-Based Therapies in Type 2 Diabetes and Obesity: A Narrative Review

  • Jana Makuc1,2,3
  • Miodrag Janić3,4
4 affiliations
  1. 1Topolšica Hospital, Topolšica 64, 3326 Topolšica, Slovenia
  2. 2Community Health Centre Ravne na Koroškem, Ob Suhi 11, 2390 Ravne na Koroškem, Slovenia
  3. 3Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
  4. 4Department of Endocrinology, Diabetes, and Metabolic Diseases, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia
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Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide have transformed the treatment of type 2 diabetes mellitus (T2DM) and obesity. Although these agents share an incretin-based mode of action, they differ in structure, receptor pharmacology, pharmacokinetics, formulation, and titration schedule, and the individual treatment response is highly heterogeneous. Switching between agents occurs in roughly one in four to one in three patients in real-world practice, yet no standardized protocol exists: recommendations rest largely on expert consensus, and no official dose-equivalence chart has been issued. This narrative review critically evaluates evidence for switching and cross-titration between incretin-based therapies; summarizes, insofar as they inform switching decisions, the pharmacological diversity and response heterogeneity that motivate switching; and translates the evaluated evidence into a stepwise practical switching algorithm, developed by the authors as an evidence-informed expert synthesis that has not been formally validated. Special populations, persistence, discontinuation, weight regain, and the emerging pipeline of multi-agonists and oral small molecules are addressed where they modify switching decisions. Until the evidence matures, individualized reason-specific transitions that preserve the continuity of incretin-based therapy offer the most defensible framework for practice.

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Cite

BibTeXRIS
BibTeX
@article{makuc2026practical,
  title = {{Practical Challenges of Switching and Cross-Titration Between Incretin-Based Therapies in Type 2 Diabetes and Obesity: A Narrative Review}},
  author = {Jana Makuc and Miodrag Janić},
  journal = {Journal of Clinical Medicine},
  year = {2026},
  month = oct,
  doi = {10.3390/jcm15218295},
  url = {https://www.mdpi.com/2077-0383/15/21/8295},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Practical Challenges of Switching and Cross-Titration Between Incretin-Based Therapies in Type 2 Diabetes and Obesity: A Narrative Review
AU  - Jana Makuc
AU  - Miodrag Janić
PY  - 2026
DA  - 2026/10/24
JO  - Journal of Clinical Medicine
DO  - 10.3390/jcm15218295
UR  - https://www.mdpi.com/2077-0383/15/21/8295
AB  - Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide have transformed the treatment of type 2 diabetes mellitus (T2DM) and obesity. Although these agents share an incretin-based mode of action, they differ in structure, receptor pharmacology, pharmacokinetics, formulation, and titration schedule, and the individual treatment response is highly heterogeneous. Switching between agents occurs in roughly one in four to one in three patients in real-world practice, yet no standardized protocol exists: recommendations rest largely on expert consensus, and no official dose-equivalence chart has been issued. This narrative review critically evaluates evidence for switching and cross-titration between incretin-based therapies; summarizes, insofar as they inform switching decisions, the pharmacological diversity and response heterogeneity that motivate switching; and translates the evaluated evidence into a stepwise practical switching algorithm, developed by the authors as an evidence-informed expert synthesis that has not been formally validated. Special populations, persistence, discontinuation, weight regain, and the emerging pipeline of multi-agonists and oral small molecules are addressed where they modify switching decisions. Until the evidence matures, individualized reason-specific transitions that preserve the continuity of incretin-based therapy offer the most defensible framework for practice.
SN  - 2077-0383
ER  -