Similar progression of diabetic retinopathy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: a long-term, randomised, open-label study.
OBJECTIVE
This long-term study was designed to further characterise the retinal safety profile of insulin glargine and human neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes mellitus.


METHODS
An open-label, 5 year, randomised (1:1), multicentre, stratified, parallel-group study conducted in the USA and Canada enrolled individuals with type 2 diabetes and either no or non-proliferative retinopathy (less than severe; Early Treatment Diabetic Retinopathy Study [ETDRS] level less than 53 in both eyes) who were treated with oral hypoglycaemic agents (OHAs) alone, insulin alone or OHAs with insulin for >/=3 months prior to study entry and a baseline HbA(1c) level of 6.0-12.0%. Patients were randomised by the investigator according to the centralised interactive voice response system to receive twice-daily NPH insulin (n = 509) or once-daily basal insulin glargine (n = 515). The investigator was not blinded to the treatment group to which each participant had been assigned. The main objective of this study was to compare the progression of diabetic retinopathy between treatment groups by analysing the percentage of patients with three or more step progression in the ETDRS retinopathy patient-level severity scale after treatment with either basal insulin. Masked, centralised grading of seven-field stereoscopic fundus photographs was used.


RESULTS
Similarly sustained glycaemic control was observed in both the insulin glargine and NPH insulin treatment groups. Despite a slightly greater severity of diabetic retinopathy for the insulin glargine group at baseline, three or more step progression in ETDRS score from baseline to end-of-study was similar between treatment groups (14.2% [53/374] of insulin glargine-treated patients vs 15.7% [57/363] of NPH-treated patients); the difference in the incidence of progression was -1.98% (95% CI -7.02, 3.06%). Other measures of retinopathy-the development of proliferative diabetic retinopathy and progression to clinically significant macular oedema-occurred to a similar degree in both treatment groups. No other safety issues, such as unexpected adverse events for either insulin emerged during the 5 year study. However, NPH insulin treatment was associated with a higher incidence of severe hypoglycaemia compared with insulin glargine.


CONCLUSIONS
This study shows no evidence of a greater risk of the development or progression of diabetic retinopathy with insulin glargine vs NPH insulin treatment in patients with type 2 diabetes mellitus.


BACKGROUND
ClinicalTrials.gov NCT00174824


BACKGROUND
This study was sponsored by sanofi-aventis.
Rosenstock
J
J
Dallas Diabetes and Endocrine Center at Medical City, 7777 Forest Lane C-685, Dallas, TX, 75230, USA. juliorosenstock@dallasdiabetes.com
Fonseca
V
V
McGill
J B
JB
Riddle
M
M
Hallé
J-P
JP
Hramiak
I
I
Johnston
P
P
Davis
M
M
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002170:Canada; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000627:therapeutic use*; D049528:Insulin, Long-Acting; D038622:Internationality; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D014481:United States
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D007336:Insulin, Isophane; D049528:Insulin, Long-Acting