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GLP-1 RECEPTOR AGONIST (GLP-1 RA)

STUDY DETAILS

Title: Effects of semaglutide on Chronic Kidney Disease in patients with Type 2 Diabetes [see Ref. 1].

Year of Publication: 2024

Journal: The New England Journal of Medicine

Study Type: Randomized, double-blind study comparing semaglutide with placebo. The semaglutide dose was escalated up to 1 mg weekly via subcutaneous administration.

Sponsored by: Novo Nordisk

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Number of Patients: 3,533 (1,767 in the semaglutide group and 1,766 in the placebo group)

Evaluation Period: Average of 3.4 years

Inclusion Criteria: Patients older than 18 years with chronic kidney disease and type 2 diabetes, treated with an ACE inhibitor or ARB at the maximum tolerated dose; with:

  • Albumin-to-creatinine ratio of 300–5000 if eGFR ≥50 ml/min/1.73 m², or

  • Albumin-to-creatinine ratio of 100–5000 if eGFR 25 to <50 ml/min/1.73 m²

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Patient Characteristics:

  • Average age: 66.6 years

  • Semaglutide group: 70.6% men  |  Placebo group: 68.9% men

  • eGFR distribution (semaglutide group): 

12.3%: eGFR 25 to <30 ml/min  |  37.7%: eGFR 30 to <45 ml/min  |  29.1%: eGFR 45 to <60 ml/min  |  20.7%: eGFR ≥60 ml/min

  • Baseline mean eGFR (semaglutide group): 46.9 ± 15.6 ml/min/1.73 m² (Stage 3a)

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RESULTS

In the semaglutide group, 331 of 1,767 patients (18.7%) reached the primary outcome of major kidney disease events, compared to 410 of 1,766 patients (23.2%) in the placebo group.

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eGFR Findings

The semaglutide group had an average annual decline of 2.19 ml/min/1.73 m², compared to 3.36 ml/min/1.73 m² in the placebo group, with an intergroup difference of 1.16 ml/min per year in favor of semaglutide.

Patients already receiving SGLT2 inhibitors or non-steroidal mineralocorticoid receptor antagonists were allowed to continue those treatments.

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  • During the first 12 weeks:

    • Semaglutide: −1.07 ml/min

    • Placebo: −1.05 ml/min

  • From week 12 to the end of the study:

    • Semaglutide: −2.36 ml/min/year

    • Placebo: −3.30 ml/min/year

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Its mechanism of action may include:

  • Reduction of inflammation, oxidative stress, and fibrosis

  • Decreased cellular expression of pro-inflammatory and pro-fibrotic mediators

Cited References

  1. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on Chronic Kidney Disease in patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109-121. https://www.nejm.org/doi/full/10.1056/NEJMoa2403347.

DISCLAIMER: This website provides educational information about Chronic Kidney Disease and published medical research. It is not intended to diagnose disease, recommend treatment, replace medical consultation, or instruct patients to start, stop or modify medications or kidney replacement therapy. Treatment decisions should be made by a qualified healthcare professional based on the individual patient's clinical condition.

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