5-Year Study Published in Diabetologia Demonstrated Long-Term Safety of Lantus Compared to NPH
- Long-term study found no increased progression of retinopathy in Lantus(R) over NPH treatment regimen -
BRIDGEWATER, N.J., July 6
/PRNewswire-FirstCall/ -- Sanofi-aventis (EURONEXT: SAN and NYSE:
SNY) announced today that the results of the long-term, 5-year
study of Lantus(R) (insulin glargine [rDNA] injection) versus NPH
insulin on progression of retinopathy in patients with type 2
diabetes, published on-line in Diabetologia (DOI
10.1007/s00125-009-1415-7) showed similar effects on retinopathy
and overall safety in the two treatment groups. This is the longest
controlled study ever reported using insulin glargine.
Diabetic retinopathy is a major cause of
blindness in patients with diabetes. It is a progressive disease
that results from cellular proliferation within the eye. The
stimulation of IGF1 receptors is involved in this process. In the
study of patients with retinopathy, the progression of diabetic
retinopathy was similar in the two treatment groups over the
long-term course of treatment.
This indicates that Lantus does not have
mitogenic effects different from the human NPH insulin within the
eye.
"This 5-year study is the longest randomized
controlled study with insulin glargine versus NPH human insulin,"
said lead investigator Julio Rosenstock, MD, Director of the Dallas
Diabetes and Endocrine Center at Medical City and also Clinical
Professor of Medicine, University of Texas Southwestern Medical
School. "This study demonstrated no evidence of a greater risk of
progression of retinopathy with insulin glargine."
The 5-year open-label study was specifically
designed to further characterize the retinal safety profile of
Lantus(R) versus NPH in 1024 patients (Lantus(R) once daily: 515
patients; NPH twice daily: 509 patients). Retinopathy progression
was assessed using serial fundus photography.
Progression was evaluated using the Early
Treatment Diabetic Retinopathy Study (ETDRS) scale; the scores at
study end were similar in both treatment groups (Lantus(R): 14.2%,
NPH: 15.7%; 95% CI: -7.02, 3.06). As per protocol, the study aimed
to achieve similar levels of glycemic control in both groups, in
order to avoid introducing bias on the primary retinopathy
end-point that could be related to differences in blood glucose
control. Both groups had comparable HbA1c at study end (mean HbA1c
improved from a baseline of 8.4% and 8.3% to 7.8% and 7.6% for all
patients in the insuline glargine and NPH insulin groups
respectively). NPH insulin was associated with a significantly
greater incidence of severe hypoglycemia than was insulin glargine
(11.1% vs 7.6% respectively, p=0.0439) and mean yearly rates of
symptomatic hypoglycemia (7.08+/-16.49 vs 5.13+/-12.79,
p=0.0017).
There was no observable trend for a difference
in the incidence of serious adverse events including cancer, as
well as adverse events leading to study withdrawal. The most common
adverse events in the study were: upper respiratory tract infection
(glargine 149 [29%], NPH 169 [33.6%]), peripheral edema (glargine
103 [20%], NPH 114 [22.7%]), and arthralgia (glargine 73 [14.2%],
NPH 81 [16.1%]).
About the study
This long-term study was designed to further
characterize the retinal safety profile of insulin glargine
(glargine) and human neutral protamine Hagedorn insulin (NPH) in
patients with type 2 diabetes mellitus.
This was an open-label, 5-year, randomized
(1:1), multicentre, stratified, parallel-group study comparing
patients treated with either twice-daily NPH (n=509) or once-daily
basal glargine (n=515).
The main objective of this study was to compare
the progression of diabetic retinopathy between treatment groups by
analyzing the percentage of patients with greater than or equal to
3-step progression in the Early Treatment Diabetic Retinopathy
Study (ETDRS) retinopathy patient-level severity scale after
treatment with either insulin. Masked, centralized grading of
seven-field stereoscopic fundus photographs was used.
Main characteristics of the population were the
following and well balanced between groups: : mean age 55, 54%
males, mean baseline HbA1c 8.4 vs 8.3% (glargine vs NPH) diabetes
duration 11 years, and about 70% of the population was already
treated with insulin prior to study entry.
Similarly sustained glycaemic control was
observed in both the glargine and NPH treatment groups. Despite a
slightly greater severity of diabetic retinopathy for the
glargine-treated group at baseline, greater than or equal to 3-step
progression in ETDRS score from baseline to end-of-study was
similar between treatment groups (14.2% [53/374] of
glargine-treated patients vs 15.7% [57/363] of NPH-treated
patients). 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. Rates of symptomatic and clinically important
hypoglycaemia were significantly lower in the glargine group: NPH
insulin was associated with a significantly greater incidence of
severe hypoglycemia than was insulin glargine (11.1% vs 7.6%
respectively, p=0.0439) and mean yearly rates of symptomatic
hypoglycemia (7.08+/-16.49 vs 5.13+/-12.79, p=0.0017). Body weight
gain tended to be greater with NPH insulin compared with insulin
glargine treatment, with a baseline to endpoint increase in mean
body weight of 3.7 kg for insulin glargine and 4.8 kg for NPH
insulin (ITT population; p=0.0505). No other safety issues for
either insulin emerged during the 5-year study.
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company, discovers, develops and distributes therapeutic solutions
to improve the lives of everyone. Sanofi-aventis is listed in Paris
(EURONEXT: SAN) and in New York (NYSE:SNY) .
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Contact: Carrie Melia - sanofi-aventis,
+1-908-981-6486, carrie.melia@sanofi-aventis.com
US.GLA.09.07.021
Source: sanofi-aventis
CONTACT: Carrie Melia, sanofi-aventis,
+1-908-981-6486,
carrie.melia@sanofi-aventis.com
carrie.melia@sanofi-aventis.com
Web Site: http://www.sanofi-aventis.us/
