Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy
Open accessAbstract
BACKGROUND: Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors in persons with type 2 diabetes. METHODS: In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure; the rates of end-stage renal disease and cardiovascular events; and the rate of death from all causes. RESULTS: After five years, the change in the glomerular filtration rate was -17.5 ml per minute per 1.73 m2 (where the minus sign denotes a decrement) in the telmisartan-treated subjects, as compared with -15.0 ml per minute per 1.73 m2 in the enalapril-treated subjects; the treatment difference was thus -2.6 ml per minute per 1.73 m2 (95 percent confidence interval, -7.1 to 2.0 ml per minute per 1.73 m2)[corrected] The lower boundary of the confidence interval, in favor of enalapril, was greater than the predefined margin of -10.0 ml per minute per 1.73 m2, indicating that telmisartan was not inferior to enalapril. The effects of the two agents on the secondary end points were not significantly different after five years. CONCLUSIONS: Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes. These findings do not necessarily apply to persons with more advanced nephropathy, but they support the clinical equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events.
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Among 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 [75]
The paper’s introductory passage reports that ARBs reduced progression to end-stage renal failure in earlier studies of people with type 2 diabetes and overt albuminuria. But this trial enrolled only people with type 2 diabetes and early nephropathy, required baseline GFR above 70 mL/min/1.73 m² (Subjects; page unavailable), and compared an ARB with an ACE inhibitor rather than testing either against no such therapy. It does not establish the claimed ESKD-risk reduction for people with type 1 or type 2 diabetes meeting the stated eGFR and UACR thresholds. (LLM, conf=0.89)
Experimental — accuracy not yet measuredACE inhibitors and ARBs are considered to have similar benefits and risks.
“ACE inhibitors and ARBs are considered to have similar benefits (76,77,83) and risks.”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [76]
The Abstract reports that telmisartan was not inferior to enalapril for long-term renoprotection in people with type 2 diabetes, supporting similar benefits in that setting. The safety section reports adverse events in both groups, but more discontinuations with enalapril (23% versus 17%); it does not establish that ACE inhibitors and ARBs have similar risks as classes. (LLM, conf=0.82)
Experimental — accuracy not yet measuredACE inhibitors and ARBs are considered to have similar benefits and risks.
“ACE inhibitors and ARBs are considered to have similar benefits (75,76) and risks.”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [75]
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- Authors
- Barnett, A. H., Bain, S. C., Bouter, P., Karlberg, B., Madsbad, S., Jervell, J., & Mustonen, J.
- Affiliations
- National Health Service (GB)
- Linköping University Hospital (SE)
- Hvidovre Hospital (DK)
- Oslo University Hospital (NO)
- Tampere University Hospital (FI)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2004-11-04
- Volume
- 351
- Issue
- 19
- Pages
- 1952-1961
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1984061204
- Cited by
- 910
- References
- 24
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 16 · 2023: 19 · 2022: 18 · 2021: 20 · 2020: 33 · 2019: 24 · 2018: 21 · 2017: 30 · 2016: 40 · 2015: 50 · 2014: 43 · 2013: 40 · 2012: 48
- FWCI
- 54.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Novo Nordisk
- Servier
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- type 2 diabetes, diabetic nephropathy, angiotensin receptor blockers, ACE inhibitors, telmisartan, enalapril, renal protection, glomerular filtration rate, end-stage renal disease, cardiovascular events, urinary albumin excretion, blood pressure
- MeSH terms
- Telmisartan, Adult, Aged, Angiotensin-Converting Enzyme Inhibitors, Benzimidazoles, Benzoates, Blood Pressure, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Enalapril, Female, Glomerular Filtration Rate, Humans, Male, Middle Aged, Prospective Studies, Angiotensin Receptor Antagonists
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