Key Timestamps
00:00 - Start
01:45 - SMART Trial Background
04:30 - Study Population Characteristics
06:10 - SMART Trial Results
07:35 - Dose-Dependent Effects of Semaglutide
09:15 - Filtration Markers
14:15 - Hypertension and BNP
News
Podcast
Kidney Compass: Semaglutide for Nondiabetic Kidney Disease, with Hiddo Heerspink, PhD, PharmD, at Kidney Week 2024
Key Takeaways
- The SMART trial showed semaglutide significantly reduced UACR by 52.1% in nondiabetic CKD patients with obesity.
- No significant difference in Cr-eGFR was observed between semaglutide and placebo groups at week 24.
Hiddo Heerspink, PhD, PharmD, joins the podcast during Kidney Week 2024 to discuss the SMART trial and the potential of semaglutide in people with kidney disease without diabetes.
Live from Kidney Week 2024!
In the latest episode of Kidney Compass: Navigating Clinical Trials, Hiddo Heerspink, PhD, PharmD, of the University of Groningen, after he presented the landmark SMART trial, which suggested the benefit of semaglutide (Ozempic/Wegovy) on chronic kidney disease (CKD) extend to patients without diabetes.
Presented at the American Society of Nephrology’s Kidney Week 2024 and simultaneously published in Nature Medicine, the placebo-controlled, double-blind trial evaluated semaglutide 2.4 mg in patients with obesity and nondiabetic CKD, with urine albumin-to-creatinine ratio (UACR) at week 24 as the primary outcome.
The trial enrolled 101 patients aged 18 to 75 with CKD (eGFR ≥25 mL/min/1.73m²) and a BMI ≥27 kg/m². Baseline characteristics included a mean Cr-eGFR of 65 mL/min/1.73m², median UACR of 251 mg/g, mean BMI of 36.2 kg/m², and prevalent ACE inhibitor or ARB use (87%).
Results showed a placebo-corrected UACR reduction of -52.1% (95% CI, -65.2 to -34.1; P <.0001) in the semaglutide arm by week 24, with effects sustaining 4 weeks post-treatment. No significant Cr-eGFR difference was observed between groups at week 24 (mean difference, -1.1 mL/min/1.73m²; P = .57), despite an initial decline in Cr-eGFR by week 8. Secondary outcomes included body weight and waist circumference reductions of -9.1 kg (P <.0001) and -4.4 kg (P = .04), respectively, with no observed correlation between weight and eGFR changes.
During the episode, Heerspink shares the impetus behind the SMART study, explaining how early pandemic lockdowns offered time to explore semaglutide's application for CKD without diabetes. The group delves into the study's design, patient profile, and a 52% reduction in albuminuria observed with semaglutide. They address dose-dependency, how higher doses may amplify albuminuria reduction, and the relationship between creatinine and cystatin C as filtration markers.
The conversation shifts to broader implications, including the drug’s anti-inflammatory benefits, its potential for longer-term GFR protection, and specific impacts on blood pressure and BNP levels. As Heerspink elaborates, these results underscore semaglutide’s versatility, suggesting new therapeutic avenues across kidney and cardiovascular care. The episode concludes with a look at future research needs, including additional trials to clarify semaglutide’s role in non-diabetic CKD and broader nephrology applications.
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Relevant disclosures for Heerspink include AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Chinook Therapeutics Inc., Gilead Sciences, Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis AG, Novo Nordisk A/S, Travere Therapeutics, and others. Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for Wadhwani include the National Institute of Diabetes and Digestive and Kidney Diseases, GSK, Calliditas and Travere Therapeutics.
References:
Apperloo EM, Gorriz JL, Soler MJ, et al. Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial. Nat Med. Published online October 25, 2024. doi:10.1038/s41591-024-03327-6
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