Introduction Patients with chronic kidney disease (CKD) often exhibit ectopic fat accumulation, including intermuscular adipose tissue (IMAT), which is associated with metabolic and muscular dysfunctions. This study aimed to evaluate the effects of dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on reducing IMAT and improving metabolic and physical functions in patients with CKD stage 3-4.

Methods Seven patients were recruited between April 2022 and November 2023. A 12-week dulaglutide (1.5 mg/wk) intervention was conducted with pre-and post-treatment assessments, including magnetic resonance imaging (MRI) for the IMAT evaluation and systemic physical performance battery test (SPPB) for physical performance evaluation. Their body mass indexes (BMI) were calculated and blood samples were analyzed for inflammatory and metabolic markers, including high sensitive C-reactive protein (Hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), glucose, insulin resistance (IR), total cholesterol, triglyceride, adiponectin, leptin, and leptin-adiponectin ratio (LAR) before and after treatment. Paired t-tests and Mann-Whitney U tests were used for statistical analysis, with significance set at p < 0.05.

Results Out of 58 assessed patients with CKD stage 3-4, 7 were enrolled, with 5 completing the full 12-week dulaglutide treatment. The total 7 people had a mean age of 59 years, mean BMI of 31.4 kg/m², and baseline eGFR of 31.7 mL/min/1.73m². IMAT decreased in 4 patients and increased in 3 patients, with no statistically significant changes overall (p = 0.69). The quadriceps muscle cross-sectional area (CSA) also showed no significant difference (p = 0.73). BMI and serum leptin levels significantly decreased after treatment (p < 0.05), while other inflammatory and metabolic markers, and physical performance scores showed no significant changes. No serious adverse events were reported.

Conclusions This study examined the effects of a 12-week dulaglutide treatment on IMAT accumulation in patients with CKD stage 3-4. While BMI significantly decreased, changes in IMAT were modest and not statistically significant, with potential but unproven clinical and metabolic benefits. Many metabolic and inflammatory markers improved, though not statistically significantly, and physical performance remained unchanged. Muscle CSA and function were maintained, which may alleviate concerns about potential GLP-1RA-induced muscle loss. Dulaglutide was well-tolerated, with minimal side effects. The small sample size and short duration highlight the need for further research.

Trial Registration Name of the Registry: ClinicalTrials.gov

Trial Registration Number: NCT05254418

Date of Registration: 2022-02-01

The authors have declared no competing interest.

NCT05254418

This research was supported by the U.S. Department of Veterans Affairs (Grant Number: 5I01CX001755), the National Institute of Diabetes and Digestive and Kidney Diseases (Grant Number: R01DK125794), and the National Center for Advancing Translational Sciences (Grant Number: UL1‐TR000445).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Boards of Vanderbilt University Medical Center approved the study protocol, and written informed consent was obtained from all study participants. The procedures were conducted under the principles outlined in the Declaration of Helsinki regarding the ethics of human research.

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All data produced in the present study are available upon reasonable request to the authors.