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Evaluating the effectiveness and safety of various Tirzepatide dosages in the management of Type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials

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Abstract

Purpose

Excess body fat, insulin resistance, and abnormal lipid levels signal type 2 diabetes mellitus (DM2). Globally, 536.6 million people suffer from DM2, projected to rise to 783.2 million by 2045. Obesity fuels insulin resistance and DM2 development, with weight loss significantly improving glycemic control. Titrzepatide (TZP), a dual GIP and GLP-1 receptor agonist, proves highly effective in controlling hyperglycemia, stimulating insulin secretion, and promoting weight loss. TZP, holds promise as a treatment for DM2, surpassing insulin and GLP-1. The study aimed to meticulously assess the safety and efficacy of various doses, offering insights into optimal therapeutic strategies for managing DM2.

Methods

This study aimed to comprehensively evaluate the safety and efficacy of TZP in treating DM2. The primary focus of the inclusion criteria was on trials comparing TZP with a placebo until November 23, 2023, excluding patients with certain comorbidities. Data extraction included key parameters, and outcomes were assessed for HbA1c levels, weight changes, fasting serum glucose levels, and various adverse events. Quality assessment utilized the Cochrane Collaboration’s risk-of-bias tool, and a network meta-analysis explored outcomes across different TZP dosages.

Results

This meta-analysis systematically reviewed ten studies on TZP for DM2. Results revealed significant reductions in HbA1c with TZP 10 mg (19%) and TZP 15 mg (31%) compared to TZP 5 mg (MD: -0.19 and MD: -0.32, respectively). Additionally, weight reduction was notable for TZP 10 mg (MD: -1.96) and TZP 15 mg (MD: -3.31). Fasting serum glucose showed improvement with TZP 15 mg (MD:-6.71). Gastrointestinal events increased with higher doses, yet without statistical significance. Death, nausea, diarrhea, vomiting, dyspepsia, decreased appetite, injection site reaction, hypoglycemia, treatment discontinuation, and serious adverse events showed no significant differences across doses.

Conclusion

TZP effectively lowers HbA1c and induces weight loss across its three doses for type 2 diabetes management. The higher dose (15 mg) significantly reduces fasting serum glucose, with increased adverse events observed at higher doses. Dose-specific patterns for adverse effects emphasize the need to balance therapeutic benefits and risks. Further research is crucial for refining clinical applications and understanding TZP’s role in DM2 management across doses.

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Data availability

Data available within the article. The authors confirm that the data supporting the findings of this study are available within the article.

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Authors and Affiliations

  1. Department of Medicine, Jinnah Sindh Medical University, Iqbal Shaheed Rd, Karachi, Pakistan

    Hussain Sohail Rangwala, Hareer Fatima, Mirha Ali, Muhammad Saqlain Mustafa, Muhammad Ashir Shafique & Burhanuddin Sohail Rangwala

  2. Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan

    Syed Raza Abbas

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All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

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Rangwala, H.S., Fatima, H., Ali, M. et al. Evaluating the effectiveness and safety of various Tirzepatide dosages in the management of Type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials. J Diabetes Metab Disord (2024). https://doi.org/10.1007/s40200-024-01412-8

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