Effect on Hemoglobin A1c (HbA1c) and Body Weight After Discontinuation of Tirzepatide, a Novel Glucose-Dependent Insulinotropic Peptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist: A Single-Center Case Series Study
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Introduction The purpose of this study was to examine changes in blood glucose levels and body weight after discontinuation of tirzepatide, a novel long-acting dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). Methods Nine subjects (five males, four females, age 54.3±5.4 years, body mass index 33.5±3.3 kg/m2) participating with type 2 diabetes in the SURPASS J-mono study were included. Subjects were randomized to tirzepatide 5 mg, 10 mg, 15 mg, or a dulaglutide 0.75 mg group. Fifty-two weeks after randomization, study drug administration was discontinued. To investigate progress after the end of administration, changes in hemoglobin A1c (HbA1c) and body weight were further examined two, four, and six months after discontinuation of the study drug. Results After fifty-two weeks, all tirzepatide groups had improved HbA1c and body weight compared with the dulaglutide group. At two, four, and six months after the end of study drug administration, re-elevation of HbA1c was observed in all groups. Furthermore, in the tirzepatide groups, dose-dependent weight regain was observed from an early stage. Conclusions Compared to dulaglutide, tirzepatide exhibited excellent blood-glucose-improving and weight-reducing effects. However, exacerbation of blood glucose and rebound of weight gain occurred relatively early after administration was ended. For type 2 diabetes patients who need weight loss and are prescribed tirzepatide, these findings suggest a necessity for continuous prescription or careful follow-up when stopping.
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Treatment discontinuation typically results in rapid weight regain, with the majority of this gain attributed to increases in fat mass.
“treatment discontinuation typically results in rapid weight regain4,9,10, with the majority of this gain attributed to increases in fat mass11–13”
From GDF8 and activin A blockade protects against GLP-1–induced muscle loss while enhancing fat loss in obese male mice and non-human primates (2025) · cites this paper as [9]
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- Authors
- Kubota, M., Yamamoto, K., & Yoshiyama, S.
- Affiliations
- National Hospital Organization (JP)
- Corresponding author
- Kubota, Mitsunobu
- Venue
- Cureus
- Published
- 2023-10-04
- Volume
- 15
- Issue
- 10
- Pages
- e46490-e46490
- ISSN
- 2168-8184 (ISSN-L)
- PMC
- PMC10550307
- OpenAlex
- W4387344729
- Cited by
- 16
- References
- 31
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 3 · 2023: 2
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Cureus (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- tirzepatide, drug discontinuation, type 2 diabetes, weight regain, glucose-dependent insulinotropic polypeptide, GLP-1 receptor agonists, dulaglutide, weight loss, glycemic control
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