GLP-1 receptor agonist → Kidney disease

Mechanism

The drugs slow the stomach, raise insulin when glucose is high, and cut appetite. Weight, blood pressure, and glucose then fall. Authors also name a kidney-level path: less pressure in the filter and less albumin in the urine. The trials count events and the eGFR slope, not a biopsy. Perkovic, Tuttle, Rossing and colleagues (2024) assigned 3,533 people with type 2 diabetes and chronic kidney disease to weekly semaglutide 1.0 mg or placebo. Median follow-up was 3.4 years after the trial stopped early. The primary composite was kidney failure (dialysis, a transplant, or eGFR under 15), a 50 percent eGFR drop from baseline, or death from kidney or cardiovascular causes. First events: 331 of 1767 versus 410 of 1766. Hazard ratio 0.76 (95 percent CI 0.66 to 0.88). The kidney-only pieces sat at 0.79 (0.66 to 0.94). The yearly eGFR fall was slower by 1.16 ml per minute per 1.73 m2. abstract_only. Mann, Orsted, Brown-Frandsen and colleagues (2017) reported the prespecified renal secondary of LEADER. 9,340 people with type 2 diabetes and high cardiovascular risk. Daily liraglutide or placebo. Median 3.84 years. The composite was new persistent macroalbuminuria, a persistent doubling of creatinine, end-stage kidney disease, or death from kidney disease. Events: 268 of 4668 versus 337 of 4672. Hazard ratio 0.78 (0.67 to 0.92). The cut was mostly new macroalbuminuria (161 versus 215; 0.74, 0.60 to 0.91). abstract_only. Shaman, Bain, Bakris and colleagues (2022) pooled SUSTAIN 6 and LEADER (12,637 people). Semaglutide or liraglutide cut urine albumin 24 percent versus placebo at two years and slowed a persistent 50 percent eGFR drop (hazard ratio 0.80, 0.66 to 0.97). full_text.

Caveats

Someone was assigned a pen, so the stamp is an RCT stamp. FLOW stopped early at a planned look. The primary composite includes death from heart causes, not only a kidney certificate. LEADER's renal count was a prespecified secondary. The cut was mostly new albumin in the urine, not dialysis. The pooled file restacks SUSTAIN 6 and LEADER. It is not a third assignment. FLOW is type 2 diabetes and established chronic kidney disease. LEADER is type 2 diabetes at high heart risk, not a dedicated kidney trial. Neither is a claim in lean people with healthy kidneys. Gut symptoms were the usual reason people left the drug. Did not hang the FLOW heart-failure satellite, the mineralocorticoid-receptor subgroup, or the cardiovascular-status split. Those are not a new kidney-event count. Did not hang a 24-week albuminuria trial in 101 people without diabetes, a phase-2 cotadutide file, a journal-club note, or a retrospective in advanced kidney failure. This page is a journal entry. It is not medical advice and not a reason to start or stop a drug.

Effect

odds_ratio = 0.76. FLOW HR 0.76 (0.66-0.88) major kidney events, N=3533 T2D+CKD. LEADER renal HR 0.78 (0.67-0.92), N=9340. Kidney-only FLOW 0.79.

Nodes

Named confounders

• Cigarette smoking
• Ultra-processed food intake
• Prolonged sitting
• Aerobic exercise
• Major cardiovascular events

Papers

• Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.

  V Perkovic, KR Tuttle, P Rossing, KW Mahaffey, JFE Mann, G Bakris, FMM Baeres, T Idorn · 2024 · The New England journal of medicine

• Liraglutide and Renal Outcomes in Type 2 Diabetes.

  JFE Mann, DD Ørsted, K Brown-Frandsen, SP Marso, NR Poulter, S Rasmussen, K Tornøe, B Zinman · 2017 · The New England journal of medicine

• Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER.

  AM Shaman, SC Bain, GL Bakris, JB Buse, T Idorn, KW Mahaffey, JFE Mann, MA Nauck · 2022 · Circulation