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Abstract: SA-PO893

The Effect of Semaglutide on Kidney Function: Post Hoc Analysis of Three Randomized Controlled Trials in Non-Alcoholic Fatty Liver Disease

Session Information

Category: CKD (Non-Dialysis)

  • 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials

Authors

  • Tuttle, Katherine R., Providence Medical Research Center, Spokane, Washington, United States
  • Idorn, Thomas, Novo Nordisk A/S, Søborg, Denmark
  • Jara, Maximilian Kurt, Novo Nordisk A/S, Søborg, Denmark
  • Palle, Mads Sundby, Novo Nordisk A/S, Søborg, Denmark
  • Sejling, Anne-Sophie, Novo Nordisk A/S, Søborg, Denmark
  • Groenbaek, Henning, Aarhus Universitetshospital Lever- Mave- og Tarmsygdomme, Aarhus, Midtjylland, Denmark
Background

Chronic kidney disease is a common comorbidity in non-alcoholic fatty liver disease (NAFLD). Semaglutide is being investigated in non-alcoholic steatohepatitis (NASH), a severe form of NAFLD. This post-hoc analysis pooled data from three randomized, placebo-controlled, phase 1 or 2 NAFLD trials to investigate the effects of semaglutide on kidney function.

Methods

Data from NCT03357380 (semaglutide 0.4 mg once daily [OD] for 72 weeks in NAFLD), NCT02970942 (semaglutide 0.1, 0.2, or 0.4 mg OD for 72 weeks in NASH with fibrosis stage 1–3), and NCT03987451 (semaglutide 2.4 mg once weekly [OW] for 48 weeks in compensated NASH cirrhosis) were included. Placebo arms were pooled, as were the semaglutide 0.4 mg OD arms in NCT03357380 and NCT02970942, and the semaglutide 2.4 mg OW arm in NCT03987451 (NCT02970942 semaglutide 0.1 and 0.2 mg OD arms were excluded). Annual slope of change in estimated glomerular filtration rate (eGFR) was analyzed for semaglutide vs placebo. Results were analyzed by baseline eGFR: <75 and ≥75 mL/min/1.73 m2.

Results

Baseline characteristics were comparable for semaglutide (n=163) and placebo (n=137). In eGFR <75 mL/min/1.73 m2, semaglutide appeared to have a beneficial effect on eGFR (annual slope semaglutide 5.91 mL/min/1.73 m2 [n=19], placebo –1.53 mL/min/1.73 m2 [n=19]; difference 7.45 mL/min/1.73 m2 95% confidence interval [CI] 3.12, 11.74). In eGFR ≥75 mL/min/1.73 m2 there was no treatment difference (semaglutide n=144, placebo n=118; difference 0.40 mL/min/1.73 m2 95% CI –1.12, 1.92). The test for interaction between the <75 and ≥75 mL/min/1.73 m2 groups was significant (p=0.0026). Semaglutide did not affect annual change in eGFR vs placebo in the overall population (difference 1.19 mL/min/1.73 m2 95% CI –0.24, 2.62). The difference in slopes was primarily driven by the positive slope in the eGFR <75 mL/min/1.73m2 group.

Conclusion

A potential protective effect of semaglutide on eGFR was seen in patients with NAFLD and eGFR <75 mL/min/1.73 m2. Although this post-hoc analysis had a small sample size, the results support further studies of semaglutide in NAFLD with low eGFR, irrespective of diabetes status.

Funding

  • Commercial Support – Novo Nordisk A/S