PopulationRegistry record; REDEFINE 1/2 reported weight but no renal endpoints.
Fundingindustry/sponsor of record - Novo Nordisk A/S (disclosed via registry)
Scope limitsNo human renal results as of search date; entry records the registered trial and data absence. NCT from web; date = search date.
Comparatorssemaglutide; cagrilintide; placebo
CotadutideMARKETED
renalDecrease
Moderate evidence
A PK/PD model from the same phase 2b CKD/T2D study predicted ~-45.6% UACR and ~-47.2% urinary-albumin change versus placebo at 26 weeks with 600 ug cotadutide,...
SourceYu et al., Br J Clin Pharmacol 2025;91(9):2672-2683Source
Full findingA PK/PD model from the same phase 2b CKD/T2D study predicted ~-45.6% UACR and ~-47.2% urinary-albumin change versus placebo at 26 weeks with 600 ug cotadutide, corroborating the dose-dependent antialbuminuric effect.
PopulationSecondary PK/PD modelling analysis of the phase 2 randomised controlled trial NCT04515849 (247 participants); cotadutide 100/300/600 ug vs semaglutide 1 mg vs placebo.
Scope limitsmodel-predicted (PK/PD) surrogate endpoint; same trial programme NCT04515849 as PMID39218393
Comparatorsplacebo; semaglutide 1 mg
CotadutideMARKETED
renalDecrease
Moderate evidence
In a phase 2b trial in T2D + CKD, cotadutide (GLP-1/glucagon dual agonist) dose-dependently reduced urinary albumin-to-creatinine ratio versus placebo, reaching...
SourceSelvarajah V et al., Kidney Int 2024;106(6):1170-1180Source
Full findingIn a phase 2b trial in T2D + CKD, cotadutide (GLP-1/glucagon dual agonist) dose-dependently reduced urinary albumin-to-creatinine ratio versus placebo, reaching significance at 300 ug (-43.9%) and 600 ug (-49.9%) at week 14, sustained to week 26, on top of standard of care.
PopulationPhase 2 double-blind randomised controlled trial (NCT04515849): 248 randomised; T2D + CKD (eGFR 20 to <90, UACR >50 mg/g); cotadutide 100/300/600 ug daily vs placebo, vs open-label semaglutide 1 mg.
Scope limitsphase 2b surrogate (UACR) endpoint; ~47% on background SGLT2i
Comparatorsplacebo; semaglutide 1 mg
DulaglutideMARKETED
renalDecrease
Moderate evidence
REWIND exploratory renal composite reduced with dulaglutide versus placebo (albuminuria-driven; eGFR-decline/RRT components non-significant).
SourceGerstein HC et al. (REWIND renal), Lancet, 2019;394:131-138Source
PopulationREWIND: N=9,901 T2D; median 5.4 years; exploratory analysis.
Fundingindustry - Eli Lilly and Company
Scope limitssurrogate/exploratory endpoint
Comparatorsplacebo
DulaglutideMARKETED
renalDecrease
Moderate evidence
AWARD-7: dulaglutide slowed eGFR decline and reduced UACR versus insulin glargine at 52 weeks in T2D with moderate-to-severe CKD (parent-trial primary finding; the...
Full findingAWARD-7: dulaglutide slowed eGFR decline and reduced UACR versus insulin glargine at 52 weeks in T2D with moderate-to-severe CKD (parent-trial primary finding; the captured paper reports fibrosis biomarkers).
PopulationAWARD-7 subset N=330 (dulaglutide 1.5 mg vs insulin glargine); T2D + moderate-to-severe CKD; 52 weeks; post hoc biomarker analysis.
Fundingindustry - Eli Lilly
Scope limitspost-hoc (not prespecified)
Comparatorsinsulin glargine; dulaglutide 0.75 mg
DulaglutideMARKETED
renalDecrease
Moderate evidence
AWARD-7 exploratory analysis: dulaglutide 1.5 mg reduced the composite of >=40% eGFR decline or ESKD versus insulin glargine in T2D with moderate-to-severe CKD,...
SourceTuttle KR et al. (AWARD-7 exploratory), Kidney360 2020;2(2):254-262Source
Full findingAWARD-7 exploratory analysis: dulaglutide 1.5 mg reduced the composite of >=40% eGFR decline or ESKD versus insulin glargine in T2D with moderate-to-severe CKD, concentrated in the macroalbuminuria subgroup; benefit at MATCHED glycaemia and BP argues for a glycaemia-independent renal effect.
PopulationAWARD-7 prespecified exploratory secondary analysis of a randomised controlled trial: dulaglutide 0.75/1.5 mg weekly vs daily insulin glargine; T2D + moderate-to-severe CKD (stage 3-4); 1 year; active comparator at matched glycaemia/BP.
Fundingindustry - Eli Lilly and Company (AWARD-7 sponsor; disclosed)
Scope limitsexploratory analysis (parent trial Tuttle 2018); active comparator insulin glargine at matched glycaemia/BP
Comparatorsinsulin glargine; dulaglutide 0.75 mg
DulaglutideMARKETED
renalMixed
Moderate evidence
AWARD-7 parent trial: in type 2 diabetes with moderate-to-severe CKD, dulaglutide gave HbA1c control non-inferior to insulin glargine with a slower decline in eGFR...
SourceTuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patient...Source
Full findingAWARD-7 parent trial: in type 2 diabetes with moderate-to-severe CKD, dulaglutide gave HbA1c control non-inferior to insulin glargine with a slower decline in eGFR over 52 weeks.
PopulationAWARD-7: phase-3, multicentre, open-label, randomised trial, N=577; type 2 diabetes plus moderate-to-severe CKD (stages 3-4) on ACEi/ARB; dulaglutide 1.5/0.75 mg vs daily insulin glargine, both with insulin lispro; 52 weeks; NCT01621178.
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Scope limitsopen-label (unblinded)
Comparatorsinsulin glargine
EfpeglenatideMARKETED
renalDecrease
Moderate evidence
AMPLITUDE-O: in T2D with cardiovascular disease or kidney disease plus a risk factor, efpeglenatide reduced a composite renal outcome (decreased kidney function or new...
SourceGerstein HC et al., N Engl J Med, 2021Source
Full findingAMPLITUDE-O: in T2D with cardiovascular disease or kidney disease plus a risk factor, efpeglenatide reduced a composite renal outcome (decreased kidney function or new macroalbuminuria) versus placebo (HR 0.68), a prespecified secondary alongside the MACE primary.
PopulationAMPLITUDE-O (NCT03496298): 4076 randomised (2717 efpeglenatide 4/6 mg, 1359 placebo); T2D + CVD or CKD (eGFR 25.0-59.9) + a risk factor; median follow-up 1.81 years; double-blind RCT; SGLT2i-stratified.
Scope limitsNEW-GATHER (identifier already in corpus as MACE-only finding C-EFPE-CARDIO-01; the RENAL composite was missing). Top-tier CVOT renal secondary. Net-new OBSERVATION on an EXISTING source (PMID 34215025, Gerstein NEJM 2021, DOI 10.1056/NEJMoa2108269); inherits the source's grade. Albuminuria-inclusive composite (not a hard kidney-failure-only endpoint). AMPLITUDE-O renal composite HR 0.68 (95% CI 0.57-0.79; P<0.001), 13.0% vs 18.4%, independently re-confirmed via PubMed get_article_metadata 2026-06-24. Independently compendium substance-audited 2026-06-24 (WI-2 audit agent, distinct from the wi2-fold collector); see validation_evidence.
No published study has measured a direct renal effect (natriuresis, sodium handling, GFR, renal blood flow) of selective/isolating GIP-receptor agonism, GIP infusion,...
SourceAbsence established via PubMed sweep (2026-06-21): no dual-agonist CV-outcome-trial recor...Source
Full findingNo published study has measured a direct renal effect (natriuresis, sodium handling, GFR, renal blood flow) of selective/isolating GIP-receptor agonism, GIP infusion, or GIPR antagonism in humans; renal GIP-receptor expression is sparse and the independent renal contribution of the GIP arm is unestablished. Honest gap record.
PopulationNarrative review (GIP in cardiovascular and kidney disease) attesting the absence/controversy; carries no positive attribution.
Fundingacademic / non-commercial (De Fano GIP review; no industry sponsor; disclosed)
Scope limitsanimal data; human relevance uncertain; surrogate/exploratory endpoint
An oral sodium-load study in 10 lean healthy men found that adding 6 g NaCl to an oral glucose load selectively amplified postprandial plasma GLP-1 but did NOT change...
SourceAsmar A et al., Physiol Rep 2020;8(15):e14519Source
Full findingAn oral sodium-load study in 10 lean healthy men found that adding 6 g NaCl to an oral glucose load selectively amplified postprandial plasma GLP-1 but did NOT change the postprandial GIP response; the proposed acute feed-forward natriuretic gut-kidney signal was attributed to GLP-1, with GIP showing no sodium-sensitivity.
Population10 lean healthy male participants; crossover (75 g glucose + 6 g NaCl vs glucose alone).
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitssmall sample (N~10) lean healthy men; mechanistic crossover; indirect (GIP secretion vs sodium stimulus, not a GIPR renal action)
Comparatorsglucose alone (no added NaCl)
GLP-1 (native; Physiology)MARKETED
renalIncrease
Low evidence
GLP-1 increases natriuresis principally by inhibiting the sodium-hydrogen exchanger isoform 3 (NHE3) in the renal proximal tubule, a candidate mechanism for the...
Full findingGLP-1 increases natriuresis principally by inhibiting the sodium-hydrogen exchanger isoform 3 (NHE3) in the renal proximal tubule, a candidate mechanism for the antihypertensive effect of GLP-1 receptor agonists; GLP-1 regulation of GFR is more complex and may involve atrial natriuretic peptide and the renin-angiotensin system.
PopulationReview-tier mechanism synthesis of GLP-1 renal actions (human-relevant physiology).
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsmechanism review; cannot outweigh primary; renal GLP-1R localises to arterial smooth muscle not tubular epithelium (direct-tubular NHE3 route is candidate not settled)
Glucagon (native; Physiology)MARKETED
renalIncrease
Low evidence
Acute glucagon infusion raises renal plasma flow, GFR and natriuresis at the isolated GCGR level, whereas pure GLP-1R agonism is natriuretic but does not change...
SourceFarah AE, Pharmacol Rev 1983;35(3):181-217 (Glucagon and the circulation)Source
Full findingAcute glucagon infusion raises renal plasma flow, GFR and natriuresis at the isolated GCGR level, whereas pure GLP-1R agonism is natriuretic but does not change GFR/RPF at healthy baseline; the co-agonist-minus-GLP-1 logic therefore attributes any GFR/RPF rise on a co-agonist toward the GCGR arm, with both arms independently natriuretic suggesting additive natriuresis.
PopulationReview-tier (glucagon side, Farah 1983); GLP-1 contrast poles are human-primary (Skov JCEM 2013 PMID 23463656; Asmar AJP-Endo 2015 PMID 25670826) cited as contrast only.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limits1983 review; primaries uncited at this locator; species-mixed (dog/rat micropuncture for the direct-tubular mechanism); 'large doses' qualifier limits transport to therapeutic exposures
Glucagon (native; Physiology)MARKETED
renalIncrease
Low evidence
Starvation (fasting) natriuresis has been linked to raised circulating glucagon, the likely mechanism being that glucagon increases renal excretion of organic acids by...
SourceFarah AE, Pharmacol Rev 1983;35(3):181-217 (Glucagon and the circulation)Source
Full findingStarvation (fasting) natriuresis has been linked to raised circulating glucagon, the likely mechanism being that glucagon increases renal excretion of organic acids by inhibiting their tubular reabsorption.
PopulationReview-tier synthesis; the fasting-natriuresis/glucagon link is correlational.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limits1983 review; primaries uncited at this locator; species-mixed (dog/rat micropuncture for the direct-tubular mechanism); 'large doses' qualifier limits transport to therapeutic exposures
Glucagon (native; Physiology)MARKETED
renalIncrease
Low evidence
Glucagon increased RNA concentration in glomerular tissue (a cAMP-independent effect), related to glomerular enlargement and basement-membrane thickening seen in...
SourceFarah AE, Pharmacol Rev 1983;35(3):181-217 (Glucagon and the circulation)Source
Full findingGlucagon increased RNA concentration in glomerular tissue (a cAMP-independent effect), related to glomerular enlargement and basement-membrane thickening seen in poorly controlled insulin-dependent diabetes (low insulin, high glucagon); the increased glomerular filtration of poorly controlled diabetes has been linked to the same hyperglucagonaemia.
PopulationReview-tier synthesis; chronic-hyperglucagonaemia/diabetes association data.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limits1983 review; primaries uncited at this locator; species-mixed (dog/rat micropuncture for the direct-tubular mechanism); 'large doses' qualifier limits transport to therapeutic exposures
Glucagon (native; Physiology)MARKETED
renalIncrease
Low evidence
In 24 healthy young men, a 7-day high-protein versus normal-protein diet raised glomerular filtration rate by ~13% and filtration fraction, with concurrent rises in...
SourceFrank H et al., Am J Clin Nutr 2009;90(6):1509-16Source
Full findingIn 24 healthy young men, a 7-day high-protein versus normal-protein diet raised glomerular filtration rate by ~13% and filtration fraction, with concurrent rises in plasma GLUCAGON, natriuresis, urinary albumin and urea; renal plasma flow and renal vascular resistance were unchanged.
Population24 healthy young men; 7-day high-protein (2.4 g/kg/d) vs normal-protein (1.2 g/kg/d) crossover.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
At relatively large doses glucagon increased renal plasma flow, glomerular filtration and electrolyte excretion; intra-renal-arterial injection raised electrolyte...
SourceFarah AE, Pharmacol Rev 1983;35(3):181-217 (Glucagon and the circulation)Source
Full findingAt relatively large doses glucagon increased renal plasma flow, glomerular filtration and electrolyte excretion; intra-renal-arterial injection raised electrolyte excretion on the injected side with minimal/no GFR change, indicating a DIRECT renal tubular natriuretic action probably mediated via tubular cAMP and prostaglandin formation in the ascending limb and collecting ducts.
PopulationReview-tier synthesis of glucagon renal physiology (mixed-species mechanism; gross RPF/GFR/excretion rise the human-relevant datum).
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limits1983 review; primaries uncited at this locator; species-mixed (dog/rat micropuncture for the direct-tubular mechanism); 'large doses' qualifier limits transport to therapeutic exposures
LiraglutideMARKETED
renalDecrease
Moderate evidence
LEADER prespecified secondary renal composite reduced with liraglutide versus placebo (driven by new macroalbuminuria).
SourceMann JFE et al. (LEADER renal), NEJM, 2017;377:839-848Source
PopulationLEADER: N=9,340 T2D, high CV risk; median 3.84 years; RCT.
FLOW: in T2D + CKD, semaglutide reduced the primary composite kidney outcome versus placebo; trial stopped early for efficacy. eGFR slope also less steep.
In T2D with established ASCVD, tirzepatide reduced a composite of major adverse kidney events versus dulaglutide in a prespecified exploratory analysis of...
SourceZoungas S et al. Tirzepatide vs dulaglutide on major kidney events: pre-specified explora...Source
Full findingIn T2D with established ASCVD, tirzepatide reduced a composite of major adverse kidney events versus dulaglutide in a prespecified exploratory analysis of SURPASS-CVOT. Note the comparator is an active CV-proven GLP-1RA (dulaglutide), NOT placebo, and the analysis is exploratory (not part of the confirmatory hierarchy).
PopulationPrespecified exploratory analysis of SURPASS-CVOT (NCT04255433): n=13,165 with T2D + established ASCVD; tirzepatide (max-tolerated up to 15 mg) vs dulaglutide 1.5 mg; median follow-up 4.0 years.
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