Meta-Analysis
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World J Diabetes. Feb 15, 2025; 16(2): 101282
Published online Feb 15, 2025. doi: 10.4239/wjd.v16.i2.101282
Renal effects and safety of tirzepatide in subjects with and without diabetes: A systematic review and meta-analysis
ABM Kamrul-Hasan, Shinjan Patra, Deep Dutta, Lakshmi Nagendra, AFM Muntahi-Reza, Sanja Borozan, Joseph M Pappachan
ABM Kamrul-Hasan, Department of Endocrinology, Mymensingh Medical College, Mymensingh 2200, Dhaka, Bangladesh
Shinjan Patra, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences Nagpur, Nagpur 441108, Maharashtra, India
Deep Dutta, Department of Endocrinology, CEDAR Superspeciality Clinics, Dwarka, New Delhi 110075, India
Lakshmi Nagendra, Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education & Research, Mysore 570015, India
AFM Muntahi-Reza, Department of Urology, Bangabandhu Sheikh Mujib Medical University, Dhaka 1000, Bangladesh
Sanja Borozan, Department of Endocrinology, Clinical Centre of Montenegro, Podgorica 81000, Montenegro
Sanja Borozan, Faculty of Medicine, University of Montenegro, Podgorica 81000, Montenegro
Joseph M Pappachan, Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust & Manchester Metropolitan University, Preston PR2 9HT, United Kingdom
Joseph M Pappachan, Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
Joseph M Pappachan, Department of Endocrinology, Kasturba Medical College, Manipal University, Manipal 576104, India
Author contributions: Kamrul-Hasan ABM contributed to the design, statistical analyses, performance of the research, implementation of the study and the writing of the manuscript; Patra S and Dutta D contributed to the statistical analyses, performance of the research and the writing of the manuscript; Nagendra L, Muntahi-Reza AFM and Borozan S contributed to the quality and professional revision and the writing of the manuscript; Pappachan JM supervised the manuscript preparation and editing the work in the final form.
Conflict-of-interest statement: There are no conflicts of interest among authors in relation to this work.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Joseph M Pappachan, Consultant Endocrinologist, Professor, Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust & Manchester Metropolitan University, Sharoe Green Lane, Lower Ormond St, Preston PR2 9HT, United Kingdom. drpappachan@yahoo.co.in
Received: September 9, 2024
Revised: November 13, 2024
Accepted: December 11, 2024
Published online: February 15, 2025
Processing time: 111 Days and 14.2 Hours
Abstract
BACKGROUND

Type 2 diabetes (T2D), as well as obesity, are risk factors for chronic kidney disease (CKD) and end-stage renal disease. The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately. Only limited data based on randomized controlled trials (RCTs) is currently available on the renal effects and safety profile of tirzepatide.

AIM

To explore the renal benefits and safety of tirzepatide vs controls.

METHODS

RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases. The co-primary outcomes were percent change from baseline (CFB) in urine albumin-to-creatinine ratio (UACR) and absolute CFB in estimated glomerular filtration rate (eGFR; in mL/min/1.73 m2); the secondary outcome was tirzepatide’s renal safety profile. RevMan web was used to conduct meta-analysis using random-effects models. Outcomes were presented as mean differences (MD) or risk ratios with 95% confidence intervals.

RESULTS

Fifteen RCTs (n = 14471) with mostly low risk of bias (RoB) were included. Over 26-72 weeks, tirzepatide 10 mg [MD -26.95% (-40.13, -13.76), P < 0.0001] and 15 mg [MD -18.03% (-28.58, -7.47), P = 0.0008] were superior to placebo in percent reductions of UACR. Tirzepatide, at all doses, outperformed insulin in percent reductions of UACR. Compared to the placebo, the percent UACR reduction was greater in subjects with T2D than those with obesity but without T2D (MD -33.25% vs -7.93%; P = 0.001). The CFB in eGFR with all doses of tirzepatide was comparable [5 mg: MD 0.36 (-1.41, 2.14); 10 mg: MD 1.17 (-0.22, 2.56); 15 mg: MD 1.42 (-0.04, 2.88)]; P > 0.05 for all] vs insulin. Tirzepatide (pooled and separate doses) did not increase the risks of adverse renal events, urinary tract infection, nephrolithiasis, acute kidney injury, and renal cancer compared to the placebo, insulin, and glucagon-like peptide-1 receptor agonists.

CONCLUSION

Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D, with a reassuring renal safety profile. Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide, which might also prevent eGFR decline and worsening of CKD.

Keywords: Tirzepatide; Type 2 diabetes; Obesity; Urine albumin creatinine ratio; Estimated glomerular filtration rate; Renal safety; Acute kidney injury; Chronic kidney disease

Core Tip: It is important to appraise the renal impacts and safety profile of Tirzepatide for optimal use of this molecule by clinicians for managing patients with type 2 diabetes (T2D), the most common cause of chronic kidney disease across the globe. Based on 15 randomized controlled trials (RCTs) with mostly low risk of bias involving 14471 participants, this systematic review identified that Tirzepatide significantly reduces urine albumin-to-creatinine ratio compared to placebo and insulin, with a neutral impact on estimated glomerular filtration rate (eGFR) in individuals with T2D and obesity without T2D. Moreover, tirzepatide does not appear to increase the risks of renal adverse events. Larger and longer-term RCTs are warranted to prove the renal benefits of tirzepatide and its potential to prevent eGFR decline in patients.