Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38
Open accessAbstract
Objective: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. Design: Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of <150/85 mm Hg (with the use of an angiotensin converting enzyme inhibitor captopril or a β blocker atenolol as main treatment) with less tight control aiming at a blood pressure of <180/105 mm Hg. Setting: 20 hospital based clinics in England, Scotland, and Northern Ireland. Subjects: 1148 hypertensive patients with type 2 diabetes (mean age 56, mean blood pressure at entry 160/94 mm Hg); 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years. Main outcome measures: Predefined clinical end points, fatal and non-fatal, related to diabetes, deaths related to diabetes, and all cause mortality. Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography. Results: Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control (144/82 mm Hg) compared with the group assigned to less tight control (154/87 mm Hg) (P<0.0001). Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24% in diabetes related end points (95% confidence interval 8% to 38%) (P=0.0046), 32% in deaths related to diabetes (6% to 51%) (P=0.019), 44% in strokes (11% to 65%) (P=0.013), and 37% in microvascular end points (11% to 56%) (P=0.0092), predominantly owing to a reduced risk of retinal photocoagulation. There was a non-significant reduction in all cause mortality. After nine years of follow up the group assigned to tight blood pressure control also had a 34% reduction in risk in the proportion of patients with deterioration of retinopathy by two steps (99% confidence interval 11% to 50%) (P=0.0004) and a 47% reduced risk (7% to 70%) (P=0.004) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study (ETDRS) chart. After nine years of follow up 29% of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures. Conclusion: Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinically important reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy, and deterioration in visual acuity.
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Hypertension is more prevalent in people with T2D than in the general population, and hypertension predicts progression to T2D.
“Hypertension is not only more prevalent in persons with T2D than in the general population, but hypertension also predicts progression to T2D.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [182]
The Introduction states that hypertension is more prevalent in people with type 2 diabetes than in the general population. It describes hypertension as a risk factor for microalbuminuria and retinopathy, not as a predictor of progression to type 2 diabetes. Searches for that prediction and for new-onset diabetes found no supporting passage. (LLM, conf=0.89)
Experimental — accuracy not yet measuredAntihypertensive therapy reduces the risk of albuminuria.
“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 [69]
Antihypertensive therapy reduces the risk of albuminuria.
“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 [70]
In the UKPDS trial, intensive blood pressure management in people with type 2 diabetes reduced the risk for heart failure by 56%.
“in the UK Prospective Diabetes Study (UKPDS) trial, intensive blood pressure management in people with type 2 diabetes reduced the risk for heart failure by 56% (276).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [276]
In the UKPDS trial, intensive blood pressure management in people with type 2 diabetes reduced the risk for heart failure by 56%.
“For example, in the UK Prospective Diabetes Study (UKPDS) trial, intensive blood pressure management in people with type 2 diabetes reduced the risk for heart failure by 56% (273).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [273]
Trials of interventions for single risk factors have shown efficacy in reducing the development and progression of complications.
“However, trials of interventions for single risk factors have shown efficacy in reducing the development and progression of complications.[4][5][6][7][8][9]”
From Effect of a multifactorial intervention on mortality in type 2 diabetes (2008) · cites this paper as [5]
Once diagnosed with hypertension, a person is 2.5 times more likely to be diagnosed with T2D within the next five years.
“Once diagnosed with hypertension, an individual is 2.5 times more likely to be diagnosed with T2D within the next 5 years.181,182”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [182]
The Introduction says hypertension and type 2 diabetes commonly coexist, while Subjects and methods describes a trial enrolling people who already had type 2 diabetes. Neither section reports whether a hypertension diagnosis predicts a type 2 diabetes diagnosis within five years. Searches for the claimed 2.5-fold risk and five-year sequence found no supporting passage in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThiazolidinediones increased the risk of heart failure hospitalization in several trials.
“Thiazolidinediones increased the risk of HF hospitalization in several trials and are not recommended in patients with diabetes and symptomatic HF. 165,[565][566][567]”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [566]
Pioglitazone is associated with an increased risk of incident heart failure in patients with diabetes.
“Pioglitazone is associated with an increased risk of incident HF in patients with diabetes and is not recommended for glucose-lowering treatment in patients at risk of HF (or with previous HF).165,566 III A”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [566]
In a UKPDS substudy, there was a marked significant 44% risk reduction for stroke and a non-significant 21% risk reduction for myocardial infarction associated with a 10 mmHg reduction in systolic blood pressure and a 5 mmHg reduction in diastolic blood pressure.
“There was a marked and significant 44% risk reduction for stroke and a non-significant 21% risk reduction for myocardial infarction associated with a 10 mmHg reduction in SBP and a 5 mmHg reduction in DBP.”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [441]
Randomized clinical trials have demonstrated the benefit (reduction of CHD events, stroke, and nephropathy) of lowering blood pressure to <140 mmHg systolic and <80 mmHg diastolic in individuals with diabetes.
“Randomized clinical trials have demonstrated the benefit (reduction of CHD events, stroke, and nephropathy) of lowering blood pressure to <140 mmHg systolic and <80 mmHg diastolic in individuals with diabetes (160,163–165).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [163]
Evidence for distinct advantages of RAS inhibitors on CVD outcomes in diabetes remains conflicting.
“Though evidence for distinct advantages of RAS inhibitors on CVD outcomes in diabetes remains conflicting (163,182), the high CVD risks associated with diabetes, and the high prevalence of undiagnosed CVD, may still favor recommendations for their use as first-line hypertension therapy in people with diabetes (160).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [163]
Control of blood pressure can reduce the development of nephropathy.
“The UKPDS provided strong evidence that control of blood pressure can reduce the development of nephropathy (163).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [163]
Lowering blood pressure decreases the progression of retinopathy.
“Lowering blood pressure has been shown to decrease the progression of retinopathy (163).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [163]
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- Authors
- UK Prospective Diabetes Study Group
- Corresponding author
- UK Prospective Diabetes Study Group,
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 1998-09-12
- Volume
- 317
- Issue
- 7160
- Pages
- 703-713
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- OpenAlex
- W3198570063
- Semantic Scholar
- 0689ea6f352bd212c4984871f32639f9e2ef70cb
- Cited by
- 6,683
- References
- 30
- Citations by year
- 2026: 61 · 2025: 99 · 2024: 96 · 2023: 129 · 2022: 145 · 2021: 120 · 2020: 140 · 2019: 168 · 2018: 208 · 2017: 204 · 2016: 230 · 2015: 212 · 2014: 263 · 2013: 277 · 2012: 268
- FWCI
- 173.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- tight blood pressure control, type 2 diabetes, hypertension, macrovascular complications, microvascular complications, diabetic retinopathy, diabetic nephropathy, urinary albumin excretion, stroke, captopril, atenolol, ACE inhibitors, beta-blockers, all-cause mortality, diabetes mortality, retinal photocoagulation
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