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. 2025 Apr 2;10(6):1980-1992.
doi: 10.1016/j.ekir.2025.03.049. eCollection 2025 Jun.

The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity

Hiddo J L Heerspink  1 , Zeqing Lu  2 , Yu Du  2 , Kevin L Duffin  2 , Tamer Coskun  2 , Axel Haupt  2 , Mark L Hartman  2
Affiliations

The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity

Hiddo J L Heerspink et al. Kidney Int Rep. .

Abstract

Introduction: Obesity and type 2 diabetes mellitus (T2D) increase the risk of kidney disease. This study assessed changes in kidney parameters with retatrutide, an agonist of the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors.

Methods: A post hoc analysis of 2 retatrutide studies (dose range: 0.5-12 mg) was performed in participants (estimated glomerular filtration rate [eGFR] ≥ 45 ml/min per 1.73 m2) with T2D (n = 281) and with overweight or obesity without T2D (n = 338). Both studies were placebo-controlled; the T2D study included dulaglutide 1.5 mg as an active comparator. We assessed change from baseline at week 36 (T2D) and week 48 (overweight/obesity) in urine albumin-to-creatinine ratio (UACR) and eGFR derived from creatinine, cystatin C, or both.

Results: At baseline, mean eGFR derived from creatinine and median UACR were 91 ml/min per 1.73 m2 and 13 mg/g, respectively in the T2D study, and 90 ml/min per 1.73 m2 and 7 mg/g, respectively in the obesity study. In participants with T2D, retatrutide 12 mg was associated with reduced UACR compared with placebo at 36 weeks by -37.0% (95% CI: -57.3 to -7.0); eGFR was unchanged compared with placebo. In participants with overweight or obesity, retatrutide 8 mg and 12 mg, compared with placebo at 48 weeks, was associated with decreased UACR by -28.0% (95% CI: -46.0 to -4.1) and -31.5% (95% CI: -49.3 to -7.4), respectively, and with increased eGFR derived from creatinine by 5.3 ml/min per 1.73 m2 (95% CI: 1.9-8.7) and 8.5 ml/min per 1.73 m2 (95% CI: 4.9-12.1), respectively. Similar increases in eGFR derived from cystatin C and combined creatinine-cystatin C eGFR were observed. Because most patients had normal albuminuria, the absolute reduction in UACR was modest.

Conclusion: Higher doses of retatrutide were associated with reduced UACR in participants with T2D and obesity, and with increased eGFR in participants with obesity but not in those with T2D.

Keywords: albuminuria; eGFR; glucagon receptor; incretin; retatrutide.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Changes in UACR with retatrutide versus placebo. The figure shows the percentage change from baseline in UACR. Data are least-squares means with error bars showing standard errors derived from the MMRM of the efficacy analysis set. The percentage change from baseline in UACR over time from the MMRM analysis for all participants in the (a) T2D study and (b) obesity efficacy population and among participants with baseline UACR of ≥30 mg/g in the (c) T2D and (d) obesity trials. MMRM, mixed model repeated measures. RETA, retatrutide. T2D, type 2 diabetes mellitus; UACR, urine albumin-to-creatinine ratio.
Figure 2
Figure 2
Changes in eGFR with retatrutide versus placebo. The figure shows the change from baseline in Cr-, Cys–, and Cr/Cys–based eGFR. Change from baseline in Cr-, Cys–, and Cr/Cys–based eGFR over time from the MMRM analysis for participants in the T2D study efficacy population (a–c) and in the obesity study safety population (d–f). Data are least-squares means with error bars showing SEs derived from the MMRM of the safety analysis set. Cr, creatinine; Cys, cystatin C; eGFR, estimated glomerular filtration rate; MMRM, mixed model repeated measures; RETA, retatrutide; T2D, type 2 diabetes mellitus.
Figure 3
Figure 3
Changes in systolic and diastolic BP with retatrutide versus placebo. Data are presented as least-squares means with error bars showing SEs derived from the MMRM of the efficacy analysis set. Changes from baseline in BP over time from the MMRM analysis for all participants in the T2D study efficacy population (a, systolic; b, diastolic) and for all participants in the obesity study efficacy population (c, systolic; d, diastolic). BP, blood pressure; MMRM, mixed model repeated measures; RETA, retatrutide; T2D, type 2 diabetes mellitus; UACR, urine albumin-to-creatinine ratio.
Figure 4
Figure 4
Correlation scatterplots for changes from baseline in bodyweight versus (a and d) Cr-, (b and e) Cys–, and (c and f) Cr/Cys–based Δ eGFR for participants in the (a–c) T2D (week 36) and (d–f) obesity (week 48) trials. Cr, creatinine; Cys, cystatin C; eGFR, estimated glomerular filtration rate; LY, life year; RETA, retatrutide; T2D, type 2 diabetes mellitus.
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References

    1. Eckel N., Li Y., Kuxhaus O., Stefan N., Hu F.B., Schulze M.B. Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses’ Health Study): 30 year follow-up from a prospective cohort study. Lancet Diabetes Endocrinol. 2018;6:714–724. doi: 10.1016/S2213-8587(18)30137-2. - DOI - PubMed
    1. Garofalo C., Borrelli S., Minutolo R., Chiodini P., De Nicola L., Conte G. A systematic review and meta-analysis suggests obesity predicts onset of chronic kidney disease in the general population. Kidney Int. 2017;91:1224–1235. doi: 10.1016/j.kint.2016.12.013. - DOI - PubMed
    1. Jager K.J., Kovesdy C., Langham R., Rosenberg M., Jha V., Zoccali C. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Kidney Int. 2019;96:1048–1050. doi: 10.1016/j.kint.2019.07.012. - DOI - PubMed
    1. de Boer I.H., Khunti K., Sadusky T., et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and kidney disease: improving global outcomes (KDIGO) Diabetes Care. 2022;45:3075–3090. doi: 10.2337/dci22-0027. - DOI - PMC - PubMed
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group KDIGO Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105:S117–S314. - PubMed

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