Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes
Open accessAbstract
BACKGROUND: It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure. METHODS: We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration, the development of end-stage renal disease, or death from any cause. We also compared them with regard to the time to a secondary, cardiovascular composite end point. RESULTS: The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group (P=0.02) and 23 percent lower than that in the amlodipine group (P=0.006). The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group (P=0.003) and 37 percent lower in the irbesartan group than in the amlodipine group (P<0.001). Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups (P=0.07 for both comparisons). These differences were not explained by differences in the blood pressures that were achieved. The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group (P=0.008) and 21 percent more slowly than in the amlodipine group (P=0.02). There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point. CONCLUSIONS: The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of the reduction in blood pressure it causes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Finerenone lowers risks of substantial GFR decline, kidney failure, HF, ASCVD events, and death in a broad T2D population.
“The nonsteroidal mineralocorticoid antagonist finerenone is also recommended for kidney and heart protection in T2D with eGFR >25 mL/min/1.73 m2, normal serum potassium concentration, and albuminuria (UACR ≥ 30 mg/g) despite a maximally tolerated dose of a renin-angiotensin system inhibitor, because it reduced risks of substantial GFR decline, kidney failure, HF and ASCVD events, and related death”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [434]
The Results describe a trial of irbesartan, not finerenone, in patients with type 2 diabetes and nephropathy. Although irbesartan reduced the risk of the renal composite outcome, the Results state that there were no significant differences in death or the cardiovascular composite outcome; the paper therefore does not support the claimed finerenone benefits. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn patients with diabetic kidney disease and increased albuminuria, large placebo-controlled trials have shown that RAS inhibitors, SGLT2 inhibitors, and finerenone each reduced the risk of progression to kidney failure.
“In patients with diabetic kidney disease with increased levels of albuminuria, large placebo-controlled trials have shown that renin-angiotensin system (RAS) inhibitors,3–5 sodium-glucose cotransporter 2 (SGLT2) inhibitors,6,7 and the non-steroidal mineralocorticoid receptor antagonist finerenone8,9 all reduced the risk of progression to kidney failure.”
From Empagliflozin in Patients with Chronic Kidney Disease (2023) · cites this paper as [4]
The Study Patients section describes people with type 2 diabetic nephropathy and substantial proteinuria. In Primary, Renal Outcome, irbesartan reduced the composite endpoint versus placebo, but the 23% lower risk of end-stage renal disease alone was not statistically significant (P=0.07). Thus this trial supports reduced renal-disease progression, but not a definitive reduction in kidney failure itself. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAmong people with type 1 or 2 diabetes with established CKD (eGFR <60 mL/min/1.73m2 and UACR >=300 mg/g creatinine), ACE inhibitor or ARB therapy reduces the risk of progression to ESKD.
“Antihypertensive therapy reduces the risk of albuminuria (67)(68)(69)(70), and among people with type 1 or 2 diabetes with established CKD (eGFR <60 mL/min/1.73m 2 and UACR $300 mg/g creatinine), ACE inhibitor or ARB therapy reduces the risk of progression to ESKD (71)(72)(73)(74)(75)(76)(77)(78)(79)(80).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [73]
The Primary, Renal Outcome section reports a 23% lower observed risk of end-stage renal disease with the ARB irbesartan than with placebo or amlodipine, but the comparison was not statistically significant (P=0.07). The Study Patients section enrolled people with type 2 diabetes using serum-creatinine and urinary-protein criteria, not the stated eGFR and UACR thresholds. The Discussion mentions ACE inhibitors and type 1 diabetes but cautions against assuming that ACE inhibitors and ARBs have equivalent effects in type 2 diabetes. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTreatment with ACE inhibitors or ARBs prevents major adverse kidney outcomes in people with diabetes and is recommended by clinical practice guidelines for people with type 2 diabetes who have or are at high risk of kidney disease.
“Treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) has been shown to prevent major adverse kidney outcomes in people with diabetes, and these drugs are recommended by clinical practice guidelines for the treatment of people with type 2 diabetes who have, or are at high risk of, kidney disease.[4][5][6][7][8]”
From SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis (2019) · cites this paper as [5]
The Results report fewer primary composite events with irbesartan, an ARB, than with placebo or amlodipine in patients with type 2 diabetes and overt nephropathy. The Discussion cautions against assuming ACE inhibitors have equivalent effects in this population. The paper does not establish prevention in people merely at high risk of kidney disease or state a clinical-practice-guideline recommendation. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe only currently approved treatment for renoprotection in patients with type 2 diabetes is renin-angiotensin system blockade.
“The only currently approved treatment for renoprotection in patients with type 2 diabetes is reninangiotensin system blockade, which was first shown to be effective 18 years ago.3,4”
From Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (2019) · cites this paper as [4]
The Conclusions (page not provided) report that irbesartan, an angiotensin-II-receptor blocker, protects against progression of nephropathy due to type 2 diabetes. The Discussion cautions against assuming equivalent effects for ACE inhibitors and receptor blockers in these patients. The paper does not establish that renin–angiotensin system blockade is the only currently approved renoprotective treatment. (LLM, conf=0.85)
Experimental — accuracy not yet measured
The eGFR ≥57% decrease outcome was selected because it is a classic outcome in diabetic nephropathy studies and is a more robust kidney failure surrogate outcome than a ≥40% decrease in eGFR, particularly when initial changes in eGFR occur.
“However, a sustained ≥57% decrease in eGFR (equivalent to doubling of serum creatinine) was selected in FIDELITY because it is a classic outcome in diabetic nephropathy studies2 , 12–14 and is a more robust kidney failure surrogate outcome than a ≥40% decrease in eGFR, particularly when initial changes in eGFR occur.14 , 15”
From Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis (2022) · cites this paper as [12]
The End Points section (page unavailable) uses doubling of baseline serum creatinine as a primary endpoint in a diabetic nephropathy trial, and the Discussion says it approximates a halving of glomerular filtration rate. The paper does not specify a sustained ≥57% eGFR decrease or compare its robustness with a ≥40% decrease, including when initial eGFR changes occur. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAmong people with type 1 or type 2 diabetes with established CKD (eGFR <60 mL/min/1.73m2 and UACR ≥300 mg/g creatinine), ACE inhibitor or ARB therapy reduces the risk of progression to kidney failure.
“Antihypertensive therapy reduces the risk of albuminuria (68-71), and among people with type 1 or 2 diabetes with established CKD (eGFR <60 mL/min/1.73m 2 and UACR ≥300 mg/g creatinine), ACE inhibitor or ARB therapy reduces the risk of progression to kidney failure (72)(73)(74)(75)(76)(77)(78)(79)(80)(81).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [74]
The Results report that irbesartan reduced the composite renal outcome in patients with type 2 diabetes and nephropathy. But the reduction in end-stage renal disease alone was not statistically significant (P=0.07). The Study Patients section used protein excretion and serum creatinine criteria, not the stated eGFR and UACR thresholds; the Discussion also cautions that the trial cannot establish equivalent effects for ACE inhibitors and ARBs. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn related studies in patients with type 1 and type 2 diabetes, the benefits of captopril or irbesartan were not tested in the presence of concurrent calcium-channel-antagonist therapy.
“In this regard, it should be noted that in related studies in patients with type 1 and type 2 diabetes, 1,28,29 the benefits of captopril or irbesartan were not tested in the presence of concurrent calcium-channel-antagonist therapy.”
From Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy (2001) · cites this paper as [28]
ACE inhibitors or ARBs have demonstrated benefit in slowing kidney disease progression.
“For many years, the only agents that had demonstrated benefit in slowing kidney disease progression were the renin angiotensin aldosterone system blockers of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) [11], [12], [13].”
From Glucagon-like peptide-1 receptor agonists in diabetic kidney disease: a review of their kidney and heart protection (2023) · cites this paper as [12]
ARBs (irbesartan/telmisartan) slowed progression from microalbuminuria (albuminuria stage A2) to overt nephropathy.
“ARBs (irbesartan/telmisartan) also slowed progression from microalbuminuria (albuminuria stage A2) to overt nephropathy.708,709”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [709]
Antagonism of the RAAS with ACE inhibitors or angiotensin II receptor blockers attenuates, but may not completely halt, the progression of kidney injury in patients with obesity, hypertension, and type 2 diabetes mellitus.
“Antagonism of the RAAS with ACE inhibitors or AngII receptor blockers also attenuates, but may not completely halt, the progression of kidney injury in patients with obesity, hypertension and T2DM67,68.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [68]
ARBs reduce the rate of progression from micro- to macroalbuminuria as well as ESRD in patients with type 2 diabetes.
“ARBs have also been shown to reduce the rate of progression from micro- to macroalbuminuria as well as ESRD in patients with type 2 diabetes (234–236).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [234]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 26 · Cited by 5,987
Research works printed but not linked: 2
- [10]10. Lee ET. Statistical methods for survival analysis. New York: John Wiley, 1992:67-78, 105-7.
- [11]11. Idem. Statistical methods for survival analysis. New York: John Wiley, 1992:250-63.
- Authors
- Lewis, E. J., Hunsicker, L. G., Clarke, W. R., Berl, T., Pohl, M. A., Lewis, J. B., Ritz, E., Atkins, R. C., Rohde, R., & Raz, I.
- Affiliations
- Rush University Medical Center (US)
- University of Iowa (US)
- Cleveland Clinic (US)
- Vanderbilt University (US)
- Heidelberg University (DE)
- Monash Medical Centre (AU)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2001-09-20
- Volume
- 345
- Issue
- 12
- Pages
- 851-860
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2044773944
- Cited by
- 5,987
- References
- 26
- Citations by year
- 2026: 125 · 2025: 166 · 2024: 164 · 2023: 186 · 2022: 177 · 2021: 180 · 2020: 182 · 2019: 155 · 2018: 158 · 2017: 161 · 2016: 182 · 2015: 178 · 2014: 227 · 2013: 215 · 2012: 261
- FWCI
- 253.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- irbesartan, amlodipine, diabetic nephropathy, type 2 diabetes, angiotensin receptor blockers, renal protection, end-stage renal disease, serum creatinine doubling, blood pressure, calcium channel blockers, cardiovascular events, hypertension, mortality, cardiovascular mortality, cardiovascular morbidity and mortality, renal function decline
- MeSH terms
- Irbesartan, Adult, Aged, Antihypertensive Agents, Biphenyl Compounds, Calcium Channel Blockers, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Humans, Hypertension, Kidney Failure, Chronic, Male, Middle Aged, Tetrazoles, Proportional Hazards Models, Amlodipine, Angiotensin Receptor Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
