Long-term follow-up of intensive glycaemic control on renal outcomes in the Veterans Affairs Diabetes Trial (VADT)
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Aims/hypothesisWe conducted an analysis of data collected during the Veterans Affairs Diabetes Trial (VADT) and the follow-up study (VADT-F) to determine whether intensive (INT) compared with standard (STD) glycaemic control during the VADT resulted in better long-term kidney outcomes.MethodsVADT randomly assigned 1791 veterans from 20 Veterans Affairs (VA) medical centres who had type 2 diabetes mellitus and a mean HbA1c of 9.4 ± 2% (79.2 mmol/mol) at baseline to receive either INT or STD glucose control for a median of 5.6 years (randomisation December 2000 to May 2003; intervention ending in May 2008). After the trial, participants received routine care through their own physicians within the VA. This is an interim analysis of the VADT-F (June 2008 to December 2013). We collected data using VA and National databases and report renal outcomes based on serum creatinine, eGFR and urine albumin to creatinine ratio (ACR) in 1033 people who provided informed consent to participate in the VADT-F.ResultsBy the end of the VADT-F, significantly more people who received INT treatment during the VADT maintained an eGFR >60 ml min−1 1.73 m−2 (OR 1.34 [95% CI 1.05, 1.71], p = 0.02). This benefit was most evident in those who were classified as at moderate risk (INT vs STD, RR 1.3, p = 0.03) or high risk (RR 2.3, p = 0.04) of chronic kidney disease on the Kidney Disease Improving Global Outcomes (KDIGO-CKD) at the beginning of VADT. At the end of VADT-F, significantly more people from the INT group improved to a low KDIGO risk category (RR 6.1, p = 0.002). During the VADT-F there were no significant differences between INT and STD for average HbA1c, blood pressure or lipid levels.Conclusions/interpretationAfter just over 11 years of follow-up, there was a 34% greater odds of maintaining an eGFR of >60 ml min−1 1.73 m−2 and of improving the KDIGO category in individuals with type 2 diabetes who had received INT for a median of 5.6 years.VADT clinical trials.gov number: NCT 00032487.
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Intensive lowering of blood glucose with the goal of achieving near-normoglycemia has been shown in large randomized studies to delay the onset and progression of albuminuria and reduce eGFR in people with type 1 diabetes and type 2 diabetes.
“Intensive lowering of blood glucose with the goal of achieving near-normoglycemia has been shown in large, randomized studies to delay the onset and progression of albuminuria and reduce eGFR in people with type 1 diabetes (52,53) and type 2 diabetes (1,(54)(55)(56)(57)(58)(59).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [59]
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Experimental — accuracy not yet measuredLowering blood glucose itself helps prevent CKD and its progression.
“Insulin alone was used to lower blood glucose in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study of type 1 diabetes, while a variety of agents were used in clinical trials of type 2 diabetes, supporting the conclusion that lowering blood glucose itself helps prevent CKD and its progression.”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [59]
The Results and Discussion (page not specified) report that intensive glucose control helped more participants with type 2 diabetes maintain eGFR above the stage 3 CKD threshold and reduced albuminuria development and progression during the trial. The broader conclusion that lowering glucose itself prevents CKD and its progression overstates these findings: the albuminuria benefit was not maintained at follow-up, and the groups did not differ significantly in ESRD or doubling of serum creatinine. (LLM, conf=0.87)
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Self-citation
- Authors
- for the VADT Study Group, Agrawal, L., Azad, N., Bahn, G. D., Ge, L., Reaven, P. D., Hayward, R. A., Reda, D. J., & Emanuele, N. V.
- Affiliations
- Edward Hines, Jr. VA Hospital (US)
- Carl T. Hayden Veterans Affairs Medical Center (US)
- VA Ann Arbor Healthcare System (US)
- Corresponding author
- Agrawal, Lily
- Venue
- Diabetologia
- Published
- 2017-11-03
- Volume
- 61
- Issue
- 2
- Pages
- 295-299
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC5747983
- OpenAlex
- W2766844376
- Semantic Scholar
- 7dc8a1135faf79493ac77f3a67197e9158807c73
- Cited by
- 92
- References
- 17
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 19 · 2020: 8 · 2019: 9 · 2018: 7 · 2017: 1
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 HX000237, I01 HX000681)
- Health Services Research and Development
- Centers for Medicare and Medicaid Services
- National Heart, Lung, and Blood Institute (R01HL067690, R01HL094775)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK092926)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- tight glycemic control, type 2 diabetes, chronic kidney disease, estimated glomerular filtration rate, HbA1c, veterans, long-term renal outcomes, albuminuria, serum creatinine, VADT, follow-up study, diabetes complications, renal function preservation, risk stratification, serum lipids
- MeSH terms
- Serum Albumin, Human, Blood Glucose, Creatinine, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Female, Follow-Up Studies, Glomerular Filtration Rate, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Kidney, Male, Veterans, Treatment Outcome
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