Sanofi presented results from the landmark ORIGIN trial (Outcome
Reduction with Initial Glargine Intervention) at the American Diabetes
Association 72nd Scientific sessions. The key findings showed
that, compared to standard care, Lantus® (insulin glargine
[rDNA] injection) had no statistically significant positive or negative
impact on cardiovascular (CV) outcomes versus standard care during the
study period and that there was no association between insulin glargine
use and increased risk of any cancer. Furthermore, the study findings,
which are also published online in the New England Journal of Medicine
(NEJM), showed that insulin glargine delayed progression
from pre-diabetes to Type 2 diabetes (T2DM).
ORIGIN was a six-year randomised clinical trial designed to assess the
effects of treatment with insulin glargine versus standard care on CV
outcomes. The study involved over 12,500 participants worldwide with
pre-diabetes or early Type 2 diabetes mellitus and high CV risk, with
6,264 participants randomised to receive insulin glargine titrated to
achieve fasting normoglycaemia. There were two coprimary composite
cardiovascular outcomes. The first was death from cardiovascular causes,
nonfatal myocardial infarction, or nonfatal stroke, and the second was a
composite of any of these events, a revascularisation procedure
(cardiac, carotid, or peripheral), or hospitalisation for heart failure.
Other adjudicated outcomes were a composite microvascular outcome,
incident cases of diabetes in participants without baseline diabetes,
all-cause mortality, and new or recurrent cancers.
Professor Melanie Davies, UK Principle Investigator ORIGIN and Professor
of Medicine Leicester University Hospitals NHS Trust commented, "ORIGIN
is an impressive study delivered by an international collaborative
addressing a clinically important question. It was demonstrated, in
these high risk CV patients, that the use of insulin glargine confirmed
no additional benefit in terms of CV outcomes. But it demonstrated that
insulin glargine was a highly effective agent in achieving and
She continued, "An additional important outcome of this study is that it
provides conclusive evidence in the context of this long duration
clinical trial that there was no increase in cancer associated with
The study demonstrated that achieving fasting normoglycaemia did not
affect CV outcomes in these participants with early dysglycaemia during
the study period (first co-primary endpoint: Hazard Ratio [HR]: 1.02;
95% confidence interval [CI], 0.94 to 1.11: p = 0.63, NS; and second
co-primary endpoint: HR: 1.04; 95% CI, 0.97 to 1.11: p = 0.27, NS).
Insulin glargine maintained targeted long-term glycaemic control (median
fasting plasma glucose 5.2 mmol/L and HbA1c 6.2% from
baseline 6.4%), which was sustained over the 6.2 years of follow-up.
There was no association between insulin glargine and increased
incidence of any cancer (HR: 1.00; 95% CI, 0.88 to 1.13: p = 0.97, NS).
Neither analysis of death from cancer, nor analysis of cancer at
specific sites, suggested an increased risk for the users of insulin
Results showed that insulin glargine delayed progression from pre-diabetes (impaired fasting glucose/IFG or impaired glucose tolerance/IGT) to T2DM by 28% (25% progressed with insulin glargine vs. 31% with standard care; HR: 0.72; 95% CI, 0.58 to 0.91: p = 0.006). Other secondary outcomes included a composite microvascular outcome (metrics of kidney or eye disease; (HR: 0.97; 95% CI, 0.90 to 1.05: p= 0.43), and all-cause mortality (HR: 0.98; 95% CI, 0.90 to 1.08: p= 0.70).
Mike Baxter, Consultant in Diabetes and Endocrinology and consultant to
Sanofi commented, "The results have shown that glargine treatment is a
highly effective intervention for patients with established and early
diabetes, which can achieve normoglycaemia without the need to escalate
therapy, or use multiple tablets, for at least six years. The inference
that there is a beneficial effect of glargine on the progression of
diabetes may be clinically important."
Hypoglycaemic events were infrequent. In the insulin glargine arm, the
rate of severe symptomatic hypoglycaemia was 0.01 episodes per
patient-year of exposure versus 0.003 episodes per patient-year for
standard care. Rates for overall symptomatic hypoglycaemia with insulin
glargine were 16.7 patients with events per 100 patient-years of
exposure versus 5.2 patients with events per 100 patient-years for
standard care. In addition, weight gain was modest for participants in
the insulin glargine arm, at an average of 3.5 pounds over the duration
of the study.
ORIGIN investigated the use of insulin glargine in a population in which
insulins are not typically used,2 providing new data on the
potential benefits and risks of initiation of insulin glargine therapy
earlier in the course of diabetes (average disease duration since
diagnosis at entry in trial: 5.5 years). Of the patients on insulin
glargine, 58% were free of any symptomatic hypoglycaemic episode for the
entire duration of the study.
"Our commitment to funding this vitally important long-term trial
exemplifies our aim to help identify new ways of treating and
understanding diabetes," commented Pierre Chancel, Senior Vice
President, Global Diabetes, Sanofi. "I am pleased to announce that
Sanofi will extend the observations of ORIGIN by an additional two