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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.

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