Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial.
OBJECTIVE
The aim of the present study was to investigate the effect of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in type 2 diabetic patients.


METHODS
The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) Retinal Measurements study, a substudy of ADVANCE, is a randomised (using a central, computer-based procedure) controlled 2 x 2 factorial trial comprising a double-blind comparison of blood pressure lowering with perindopril-indapamide vs placebo, and an open comparison of standard vs intensive glucose control targeting a HbA(1c) of < or = 6.5% in 1,602 diabetic patients from ADVANCE centres with access to retinal cameras conducted from 2001 to 2008. At baseline and the final visit, seven-field stereoscopic retinal photographs were taken and graded by blinded readers (gradeable baseline and final photographs from 1,241 patients). Progression of > or =2 steps in the Early Treatment of Diabetic Retinopathy Study classification (using the eye with worst grading) was the primary outcome.


RESULTS
Retinopathy progressed in 59 (4.8%) patients and developed in 128 (10.3%) patients over 4.1 years. Fewer patients on blood pressure-lowering treatment (n = 623) experienced incidence or progression of retinopathy compared with patients on placebo (n = 618), but the difference was not significant (OR 0.78; 95% CI 0.57-1.06; p = 0.12). Blood pressure-lowering treatment reduced the occurrence of macular oedema (OR 0.50; 95% CI 0.29-0.88; p = 0.016) and arteriovenous nicking compared with placebo (OR 0.60; 95% CI 0.38-0.94; p = 0.025). Compared with standard glucose control (n = 611), intensive glucose control (n = 630) did not reduce (p = 0.27) the incidence and progression of retinopathy (OR 0.84; 95% CI 0.61-1.15). Lower, borderline significant risks of microaneurysms, hard exudates and macular oedema were observed with intensive glucose control, adjusted for baseline retinal haemorrhages. These effects of the two treatments were independent and additive. Adverse events in the ADVANCE study are reported elsewhere.


CONCLUSIONS
Blood pressure lowering or intensive glucose control did not significantly reduce the incidence and progression of retinopathy, although consistent trends towards a benefit were observed, with significant reductions in some lesions observed with both interventions.


BACKGROUND
ClinicalTrials.gov ID no. NCT00145925.


BACKGROUND
Grants from Servier and the National Health and Medical Research Council of Australia.
Beulens
J W J
JW
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, GA, the Netherlands. J.Beulens@umcutrecht.nl
Patel
A
A
Vingerling
J R
JR
Cruickshank
J K
JK
Hughes
A D
AD
Stanton
A
A
Lu
J
J
McG Thom
S A
SA
Grobbee
D E
DE
Stolk
R P
RP
D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000196:embryology* / Q000209:etiology / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007190:Indapamide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000494:pharmacology / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007190:Indapamide; D020913:Perindopril