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

Abstract

Aims/hypothesis 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 patientlevel severity scale after treatment with either basal insulin. Masked, centralised grading of seven-field stereoscopic fundus photographs was used.

Does diabetes therapy influence the risk of cancer?

“…The three other observational analyses presented in this issue of Diabetologia were therefore commissioned to examine the safety of this insulin [10,24,25], and the main findings will be summarised here. Coincidentally, a further paper in this issue reports a prospective evaluation of the risk of retinopathy progression in patients treated with insulin glargine or human NPH insulin [41]. Additional safety data relating to cancer risk in this and other studies have been made available to our journal and will be published shortly.…”

“…A further safety concern requiring human studies arose when one of the early clinical trials [44] was reported to have observed a threefold increase in retinopathy progression with insulin glargine compared with human insulin [41]. Curiously, this fact is not mentioned in the original report [44], which concludes with the statement that insulin glargine has a safety profile that, apart from reduced nocturnal hypoglycaemia, is 'otherwise similar to NPH insulin'.…”

Diabetic retinopathy and insulin glargine

“…To the Editor: The recent paper by Rosenstock et al [1] published in Diabetologia claims that 'this study was specifically designed to detect differences in the incidence of retinopathy progression by fundus photography over a 5 year period' and that it demonstrated 'similar progression of diabetic retinopathy with insulin glargine (A21Gly, B31Arg,B32Arg human insulin) and neutral protamine Hagedorn (NPH) insulin'. The authors explain that, to verify progression status, a side-by-side comparison of baseline and follow-up photographs was conducted for any patient whose Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy severity scale score progressed by three steps or more, compared with baseline, at any time point during the study.…”

“…15-35% (secondary intervention group), which was clearly different from the 5 year incidence of retinopathy (change in ETDRS score of at least three steps from baseline) of approximately 5-15% in cases without retinopathy at baseline (primary prevention group) [2]. The estimate for power calculations by Rosenstock et al [1], a 20% 5 year event rate, was taken from the DCCT data [1]. However, the DCCT only included type 1 diabetic patients.…”

“…In the UK Prospective Diabetes Study on type 2 diabetic patients, cases without pre-existing retinopathy progressed much slower than those with; indeed, the 6 year event rate was less than half that in the DCCT [3]. Hence, the study by Rosenstock and colleagues [1] was considerably underpowered.…”