Cardio-kidney-metabolic protective effects of semaglutide across the spectrum of chronic kidney disease

Figure 1 The effects of semaglutide on the primary Kidney Outcome end-point in recent major clinical trials. FLOW: Evaluate Renal Function with Semaglutide Once Weekly. Primary kidney Outcome- New or worsening nephropathy: Macroalbuminuria, doubling of serum creatinine with estimated glomerular filtration rate (eGFR) ≤ 45, initiation of renal replacement, or renal death. SELECT: Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity. Primary Kidney Outcome- Composite: ≥ 50% decline in eGFR, kidney failure, or kidney-related death. SUSTAIN-6: Semaglutide Use to Stabilize and Improve Glycemic Control in Individuals with Type 2 Diabetes. Primary Kidney Outcome- New or worsening nephropathy: Macroalbuminuria, doubling of serum creatinine with eGFR ≤ 45, initiation of renal replacement, or renal death. SOUL: Semaglutide Cardiovascular Outcomes Trial. Primary Kidney Outcome- Includes: Cardiovascular death, kidney death, ≥ 50% eGFR decline, sustained eGFR < 15, or initiation of dialysis/transplant. eGFR: Estimated glomerular filtration rate; ACR: Albumin to creatine ratio.

Figure 2 Potential kidney-cardiovascular and metabolic effects of semaglutide in people with chronic kidney disease. ANP: Atrial natriuretic peptide; BP: Blood pressure; CKD: Chronic kidney disease; CV: Cardiovascular; HbA1c: Glycated haemoglobin; KIM-1: Kidney injury molecule-1; LDL-C: Low-density lipoprotein cholesterol; NF-κB: Nuclear factor-κB; NHE3: Sodium-hydrogen exchanger-3; NO: Nitric oxide; RAAS: Renin-angiotensin-aldosterone system; RAGE: Receptor for advanced glycation end products; TGF-β: Transforming growth factor-β. Created in BioRender (https://BioRender.com/yd9812v).

Figure 3 The effects of semaglutide on the average annual change in estimated glomerular filtration rate in Evaluate Renal Function with Semaglutide Once Weekly, Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity and Semaglutide Use to Stabilize and Improve Glycemic Control in Individuals with Type 2 Diabetes. FLOW: Evaluate Renal Function with Semaglutide Once Weekly; SELECT: Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity; SUSTAIN-6: Semaglutide Use to Stabilize and Improve Glycemic Control in Individuals with Type 2 Diabetes; eGFR: Estimated glomerular filtration rate; ETD: Estimated treatment difference.

Figure 4 The theoretical benefits of delaying onset of kidney failure, in terms of years gained, for patients in Evaluate Renal Function with Semaglutide Once Weekly treated with semaglutide vs placebo, if the amelioration of estimated glomerular filtration rate decline occurs a constant rate with semaglutide. eGFR: Estimated glomerular filtration rate; CKD: Chronic kidney disease; FLOW: Evaluate Renal Function with Semaglutide Once Weekly.

Figure 5 The effects of semaglutide on major kidney and cardiovascular outcomes in the Evaluate Renal Function with Semaglutide Once Weekly trial. Evaluate Renal Function with Semaglutide Once Weekly kidney outcome- New or worsening nephropathy: Macroalbuminuria, doubling of serum creatinine with estimated glomerular filtration rate (eGFR ≤ 45), initiation of renal replacement, or renal death. Major CV events: Major CV events including CV death, non-fatal myocardial infarction, or non-fatal stroke and heart failure with secondary/exploratory outcomes included hospitalization for heart failure; CV: Cardiovascular; HF: Heart failure; FLOW: Evaluate Renal Function with Semaglutide Once Weekly.