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Journal Article Ppublish

PubMed: 40236848 DOI: 10.4239/wjd.v16.i4.101731

Reasons for discontinuing tirzepatide in randomized controlled trials: A systematic review and meta-analysis.

World J Diabetes 16(4):101731

Authors: Abul Bashar Mohammad Kamrul-Hasan, Joseph M Pappachan, Deep Dutta, Lakshmi Nagendra, Mohammad Shafi Kuchay, Nitin Kapoor

Affiliations

  • Department of Endocrinology, Mymensingh Medical College, Mymensingh 2200, Dhaka, Bangladesh.
  • Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom.
  • Department of Endocrinology, KMC Medical College, Manipal University, Manipal 576104, India.
  • Department of Endocrinology, CEDAR Superspeciality Healthcare, Dwarka, New Delhi 110075, India.
  • Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education & Research, Mysore 570015, India.
  • Department of Endocrinology and Diabetes, Medanta the Medicity Hospital, Gurugram 122001, Haryana, India.
  • Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India.
  • Non-Communicable Disease Unit, Melbourne School of Population and Global Health, University of Melbourne, Carlton 3053, Victoria, Australia.

Abstract

BACKGROUND

Despite therapeutic benefits, discontinuation of tirzepatide is common in randomized controlled trials (RCTs) due to adverse events (AEs) and other causes. No previous systematic reviews have explored the reasons for discontinuing tirzepatide in the RCTs.

AIM

To explore the reasons for permanent discontinuation of tirzepatide controls [placebo, insulin, and glucagon-like peptide-1 receptor agonists (GLP-1Ras)] in RCTs.

METHODS

Relevant RCTs were systematically searched using related terms through multiple databases such as MEDLINE ( PubMed), Scopus, Cochrane Central Register, and ClinicalTrials.gov from their inception until June 20, 2024. RevMan web was used to conduct meta-analysis using random-effects models. Outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).

RESULTS

Seventeen RCTs ( = 14645), mostly having low risks of bias, were analyzed. Compared to placebo, the risk of permanent discontinuation of the study drug was substantially lower with tirzepatide 10 mg (RR: 0.69, 95%CI: 0.51-0.93, = 0.02) and similar with tirzepatide 5 mg (RR: 0.74, 95%CI: 0.47-1.17, = 0.20) and 15 mg (RR: 0.94, 95%CI: 0.68-1.31, = 0.71). Tirzepatide had identical discontinuation risks when compared to insulin at 5 mg (RR: 0.96, 95%CI: 0.75-1.24, = 0.77) and 10 mg (RR: 1.19, 95%CI: 0.77-1.82, = 0.44) doses, whereas such risk was higher with tirzepatide 15 mg than insulin (RR: 1.31, 95%CI: 1.03-1.67, = 0.03). Compared to GLP-1RA, the permanent discontinuation risk was similar with tirzepatide 5 mg (RR: 0.98, 95%CI: 0.70-1.37, = 0.90) but was higher with tirzepatide 10 mg (RR: 1.40, 95%CI: 1.03-1.90, = 0.03) and 15 mg (RR: 1.70, 95%CI: 1.27-2.27, = 0.0004). Tirzepatide, at all doses, had higher risks of AE-related discontinuation than insulin; such risks were only greater with higher doses of tirzepatide than with placebo or GLP-1RA. Discontinuation risk due to withdrawal by the study subjects was lower with tirzepatide than with placebo or insulin. Compared to the placebo, tirzepatide (all doses) conferred a lower risk of study drug discontinuation due to other causes not specifically mentioned.

CONCLUSION

The discontinuation risk is not higher in tirzepatide group than in the placebo arm. Many factors other than AEs led to drug discontinuation in the included RCTs.

MeSH

Insulin, Pharmaceutical Preparations