New data from ORIGIN

Sanofi (EURONEXT: SAN and NYSE: SNY) today announced new results from the landmark ORIGIN (Outcome Reduction with Initial Glargine INtervention) trial showing treatment with Lantus® (insulin glargine) was approximately 3-fold more likely (p<0.001) to achieve and maintain target glycemic levels, defined as HbA1C < 6.5% in this analysis, vs. standard care in individuals with pre-diabetes or early type 2 diabetes at high cardiovascular (CV) risk.

Data presented at the European Association for the Study of Diabetes (EASD) 48th Annual Meeting showed that insulin glargine use was an independent predictor of maintaining mean yearly HbA1c < 6.5% target over 5 years, vs. standard care. Similarly, a lower HbA1c baseline level was also found to predict reaching the same target.

ORIGIN was a six-year randomized clinical trial designed to assess the effects of treatment with insulin glargine vs. standard care on CV outcomes and involved over 12,500 participants worldwide with pre-diabetes (impaired fasting glycemia or impaired glucose tolerance) or early type 2 diabetes (treated at most with one oral anti-diabetic) and high CV risk. Key results reported earlier this year at the American Diabetes Association Congress (June 2012) showed insulin glargine had a neutral effect on CV outcomes and significantly reduced progression from pre-diabetes to diabetes (secondary outcome) by 28% (p=0.006).1

“This analysis shows that insulin glargine generally brought glycemic control to HbA1c <6.5%, a commonly sought target, and sustained it over 5 years. Further study of the ORIGIN data is likely to provide further insights regarding the medical benefits or risks of this approach to treatment,” stated Professor Matthew Riddle M.D., Oregon Health and Science University, USA, lead author of this ORIGIN sub-analysis.

These new findings showed that insulin glargine was more effective than standard care at maintaining glycemic control in all subgroups assessed, including age, alcohol consumption, depression, baseline HbA1c, urine albumin:creatinine ratio (ACR), diabetes and particularly in individuals with abdominal obesity (p=0.011) and greater grip strength (p<0.001).

Dr. Riccardo Perfetti, Vice President Medical Affairs, Global Diabetes, Sanofi, commented: “Contrary to conventional understanding that diabetes is a progressively worsening disease, these new results from this sub-study of ORIGIN suggest that achieving and maintaining glycemic control early with insulin glargine might positively affect the natural history of the disease.”

Safety outcomes from the new ORIGIN sub-study were not included in the presentation at the EASD 48th Annual Meeting. Hypoglycemic events as observed in the ORIGIN main study1 were infrequent: In the insulin glargine arm, the rate of severe hypoglycemia was 0.01 episodes per patient-year of exposure versus 0.003 episodes per patient-year for standard care. Rates for overall hypoglycemia 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.

In addition to more than 10 years of real life experience with Lantus® and clinical programs involving 80,000 people,2 ORIGIN and its sub-studies assert insulin glargine as the most studied basal insulin with long-term proven efficacy and established safety. Its indication is for the treatment of diabetes where insulin use is required; it does not include people with pre-diabetes.

About ORIGIN

ORIGIN (Outcome Reduction with Initial Glargine Intervention) is a unique, six-year landmark cardiovascular (CV) outcomes trial, evaluating Lantus® (insulin glargine) versus standard care in over 12,500 individuals who are at high CV risk with pre-diabetes or early type 2 diabetes mellitus. Spanning 40 countries worldwide, it is the world’s longest and largest randomized clinical trial of its type in this population, and the first to formally evaluate the effects of insulin on CV outcomes. The trial used a 2×2 factorial design to determine whether using insulin glargine to target fasting normoglycemia (FPG ≤ 95mg/dL), and separately omega-3 polyunsaturated fatty acids (PUFA), could reduce cardiovascular morbidity and/or mortality.3 Participants assigned to standard care were treated on the basis of the investigator’s best judgment and local guidelines, including lifestyle measures, dietary modifications, metformin, sulfonylureas and other oral anti-diabetic agents.

About Diabetes

Diabetes is a chronic disease that occurs in two main clinical presentations: type 1 diabetes, which is an autoimmune disease characterized by the lack of insulin (the hormone that regulates blood glucose concentrations) production by the pancreas, and type 2, a metabolic disorder in which there are two main biological defects: a deficient production of insulin and reduced ability of the body to respond to the insulin being produced. Type 1 and type 2 diabetes are characterized by an increase in blood glucose concentrations (hyperglycemia). Over time, uncontrolled hyperglycemia leads to the macrovascular and microvascular complications of diabetes. Macrovascular complications, which affect the large blood vessels, include heart attack, stroke and peripheral vascular disease. Microvascular complications affect the small blood vessels of the eyes (retinopathy), kidney (nephropathy) and nerves (neuropathy). Nearly 35 million people worldwide are living with type 1 diabetes. And, the incidence of type 2 diabetes is growing at an alarming rate, with more than 310 million people worldwide living with the condition today.

References

1. Gerstein H (ORIGIN Trail Investigators) et al. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia. New England Journal of Medicine 2012; 367: 319-328.
2. Data on file
3. ORIGIN Trial Investigators, Gerstein H, Yusuf S, et al. Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention). Am Heart J 2008;155(1): 26-32.