Sanofi-aventis announces results of research in the use of Lantus®( insulin glargine [rDNA] injection )


1. Two new meta-analyses confirm once-daily Lantus® efficacy and reduced risk of hypoglycaemia compared to NPH Insulin
2. With lower dose, Lantus® achieves similar and well tolerated glycemic control versus insulin detemir

Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced the results of new analysis that found a significantly lower risk of nocturnal hypoglycemia with Lantus® (insulin glargine [rDNA] injection) as compared to NPH insulin.  A separate post-hoc sub-analysis found a greater HbA1c and FBG reduction for elderly patients over 65 years of age taking Lantus® as compared to NPH insulin. In addition, Sanofi-aventis announced results of a head-to-head study providing further evidence on the efficacy of once-daily, 24-hour basal insulin Lantus® (insulin glargine [rDNA] injection) compared to twice-daily insulin detemir. Both the analyses and the study were presented during the 45th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Vienna.

Diabetes treatments are aimed at lowering the glucose in the blood, in order to delay the appearance of complications. Insulins are given as a substitute (Type 1) or a supplement (Type 2) to natural insulin secretion.

“Type 2 diabetes is a growing epidemic in the UAE, it is our duty as specialists to continue to explore all means to manage this disease,” said Dr. Hisham Mahmoud, Medical Director Gulf countries, Sanofi-aventis,  “There is a general misconception about insulin therapy among patients in the Middle East; they might assume that only advanced cases of diabetes succumb to this kind of therapy. Initiating insulin immediately, if patients are not achieving target glycemia, will allow better control of the disease. These studies further reinforce the early  use of insulin glargine, proving its efficacy in the treatment of diabetes.”

The first analysis demonstrated that should they be treated with Lantus®, within 6 months, 1 in 8 patients using Lantus® would avoid a confirmed symptomatic event compared to patients using NPH (p<0.0001). They also found that there was a significantly lower risk of nocturnal hypoglycemia with Lantus® treatment and that daytime symptomatic hypoglycaemia tended to be lower with Insulin Lantus® vs NPH, but the differences were not statistically significant.

“The avoidance of confirmed symptomatic hypoglycemic events with Lantus® is highly meaningful for patients,” said Professor Philip Home, Newcastle University, UK, author of the study. ”The studies also found that there was a significantly lower risk of nocturnal severe hypoglycemia, which may help patients better adhere to their insulin therapy.”

Fear of hypoglycaemia can delay insulin initiation and prevent adequate blood glucose control. Nocturnal hypoglycaemia is particularly feared by healthcare professionals and patients because it often goes unrecognised. Left undetected, hypoglycaemia can lead to increased morbidity such as sleep disturbance, morning headache, chronic fatigue or mood changes.

A second meta-analysis2 demonstrated a reduced risk of nocturnal hypoglycemia with once-daily Lantus patients over NPH. In particular, in elderly patients over 65, not only was there a reduced risk of nocturnal hypoglycemia (1.99vs 3.45 events per patient year p<0.0001), but also a greater HbA1c reduction (1.2% v 0.9% p<0.05) was achieved with Lantus over NPH insulin in a post-hoc analysis.

“Improved glycaemic control can reduce the risk of micro- and macrovascular disease. In older adults, diabetes treatment should be individualized for each patient to achieve optimal glucose control while avoiding adverse side effects,” stated Dr. Pearl Lee, University of Michigan, U.S., author of the study. “Physicians often fear hypoglycemia in the elderly. Our study demonstrates that with Lantus® one can achieve both greater efficacy and a lower risk of hypoglycaemia in comparison to NPH.”

In the head-to-head study, randomised, non-inferiority controlled clinical trial of 964 patients, patients taking Lantus® required an average daily dose of 43.5 units to achieve the primary endpoint of HbA1c below 7% without symptomatic hypoglycaemia compared to patients on insulin detemir, who received 76.5 units – an increase of 76% (p<0.001). Despite lower doses of insulin in the glargine group, Lantus® once-daily and insulin detemir twice-daily resulted in similar improvements in glycaemic control (HbA1c) and a similar risk of hypoglycaemia (primary endpoint: 27.5% vs 25.6%, p=0.52). Patients in the Lantus® arm of the study also achieved significantly lower fasting blood glucose (-63.1 mg/dL Lantus® vs -57.7 mg/dL, p<0.001).

In the study, patients taking Lantus® once-daily reported a significantly greater treatment satisfaction over insulin detemir twice-daily, with over 50% less drop-outs (4.6% vs 10.1%, p=0.001). Discontinuations in patients taking insulin detemir were primarily due to adverse events, including skin reactions. Whilst a similar rate of overall hypoglycaemia and nocturnal hypoglycaemia was observed in both arms, patients on Lantus® once-daily experienced less daytime hypoglycaemia as compared to insulin detemir (1.06 vs 1.64 events per patient year, p=0.046). Patients on insulin detemir experienced less weight gain (0.6 vs 1.4 kg, difference 0.77 kg, p<0.001).

“This study demonstrated that for insulin-naïve patients with type 2 diabetes, initiating insulin therapy with once-daily glargine achieved the same glycaemic control as twice-daily detemir, with somewhat more weight gain, but lower insulin doses” Study Investigator Hertzel Gerstein, Professor of Diabetes Medicine, Faculty of health sciences, Hamilton, Canada.

About the meta-analyses

Home, P et al: Estimating Number-Needed-to-Treat with Insulin Glargine (GLAR) Compared with NPH Insulin to Avoid a Hypoglycemic Episode in People with Type 2 Diabetes (T2D): a Meta-analysis.

Five studies conducted between 2000 and 2007 were included in the analysis of evening Lantus® injection (n=2711). Patients had a mean age of nearly 60 years, were moderately overweight (mean BMI 28.0–29.0 kg/m2) had a mean disease duration of 10 years, and were using a combination of insulin and oral glucose-lowering drugs. Most of the patients were insulin naïve. All of the patients were using a combination of insulin and oral agents.

The primary outcome was between-treatment comparison of the proportion of patients with ≥1 hypoglycaemic event differentiated into time of occurrence (daytime or nocturnal, and total events) adjusted for change in HbA1c from baseline to end of the study. Secondary endpoints were hypoglycaemic events by category/severity. The categories were severe, or symptomatic with self-monitoring blood plasma levels of <2.00 mmol/L (36 mg/dL) or <3.9 mmol/L (70 mg/dL). Severity of hypoglycaemia and the time of day of occurrence was documented for more than 97% of participants (Lantus® : n=1303, NPH: n=1338).

Lee, P et al: Safety and Efficacy of Insulin Glargine compared with NPH Insulin in older adults with T2DM. EASD 2009: Pooled Analysis

Data were pooled from four similar, international, multisite, randomized clinical trials comparing the safety and efficacy of the addition of Lantus® or NPH insulin to uncontrolled OADs patients. All patients in these trials were insulin naive, had diagnosed type 2 diabetes, and were treated with a basal insulin only (Lantus® or NPH insulin). Duration of treatment in all studies was 24 weeks.

Studies were compared for HbA1c reduction and hypoglycemic events at the end of 24 weeks in patients ≤65 (Lantus® [n=831] versus NPH [n=859]) and >65 years (Lantus® [n=215] versus NPH [n=236]).

Authors found that the rate of nocturnal hypoglycemia was statistically significantly lower with Lantus® than with NPH in both age groups studied  (below 65 and above 65 years old): (1.1 versus 2.3 average events per patient year [p<0.0001] ; and 1.3 versus 2.7 average events per patient year [p<0.005] respectively). The number of symptomatic hypoglycemic events per patient year in these older patients was 2.2 for Lantus® and 2.4 for NPH, with 0.01 severe hypoglycemic events for Lantus® and 0.03 for NPH.

Among patients 65 or younger, there was no significant difference between Lantus® and NPH in HbA1c reduction (1.26% for Lantus®, 1.20% for NPH) or FBG reduction (86 mg/dL for Lantus®, 84 mg/dL for NPH) after 24 weeks of treatment. Similar results were also found for daytime symptomatic hypoglycemic events per patient year in patients ≤65 years old (2.4 for Lantus® and 2.6 for NPH) and severe hypoglycemic events (0.03 for Lantus® and 0.04 for NPH)

There was a lower rate of daytime symptomatic hypoglycaemia confirmed by PG ≤ 56 mg/dL (3.1 mmol/L) with Lantus® treatment vs. insulin detemir (1.06 ± 3.13 vs. 1.64 ± 5.42 events/patients-year, p=0.046). Frequencies of asymptomatic, overall symptomatic, nocturnal symptomatic and severe hypoglycaemia were comparable between treatment groups. Significantly more patients in the insulin detemir group terminated the study early (10.1 vs. 4.6%, p=0.001), which was mostly related to skin reactions. Limited weight gain in both groups, although compared with the glargine group, patients on insulin detemir experienced less weight gain (0.6 versus 1.4kg, difference 0.77kg p<0.001).

About the Lantus® vs. insulin detemir study1

In the study, a total of 964 insulin-naïve patients were examined.  Patients were between 40 to 75 years of age and had type 2 diabetes for at least 1 year with sub-optimal blood glucose control using glucose-lowering drugs.

Patients were randomised and treated with Lantus® once daily, at either dinner or bedtime, or insulin detemir twice daily, both at breakfast and before dinner, along with stable doses of metformin. Thiazolidinedione treatment was halted as of insulin randomisation, but insulin secretagogues were continued or discontinued at the investigator’s discretion.

For both insulins, the starting daily dose was 0.2 U/kg, which was then titrated every 2 days by 2 units to obtain a Fasting Plasma Glucose (FPG) of <100 mg/dL (5.6 mmol/L). At baseline, mean age was 58.4 ± 8.3 yrs (mean ± standard deviation), mean type 2 diabetes duration was 9.9 ± 5.8 years, mean FPG was 189.2 ± 48.7 mg/dL, and mean HbA1c was 8.7 ± 0.9%. 27.5% and 25.6% of patients reached the primary endpoint of HbA1c <7% without confirmed hypoglycaemia. Change from baseline to endpoint HbA1c was similar with Lantus® and insulin detemir (-1.46 ±1.09 and -1.54 ± 1.11%; p=0.149), endpoint HbA1c levels were 7.2 ± 0.9% and 7.1 ± 0.9% respectively. Endpoint FBG was lower with Lantus® versus insulin detemir (108 ± 24 vs 119 ± 32mg/dL).

About SoloSTAR®

SoloSTAR® is an easy-to-use disposable pen for administration of Lantus® and Apidra®. SoloSTAR® allows to administer doses from 1 up to 80 units, in one unit increments, in one injection. SoloSTAR® offers a 33% greater maximum capacity than other disposable insulin pens, up to 80 units of insulin in one injection.

About Lantus®

Lantus® is indicated for once-daily subcutaneous administration in the treatment of adult patients with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycemia and for adult and pediatric patients (6 years and older) with type 1 diabetes mellitus. Lantus® demonstrates a peakless and sustained concentration/time profile over 24h thus reducing the risk of hypoglycemia and allowing a constant and high efficacy over 24h with one single daily injection. Lantus® is the number one prescribed insulin worldwide. Once prandial insulin is required, Apidra® is the logical partner to Lantus® .

About Apidra®

Apidra® is rapid-acting insulin analog with a unique zinc-free molecular structure that maintains a rapid onset and a short duration of action, indicated for adults, adolescents and children with diabetes. Apidra® offers patients mealtime dosing flexibility – it can be taken shortly (0-15 min) before or soon after the meal. Apidra® is also flexible for use in a wide range of patients from lean to obese.

About Diabetes

Diabetes is a chronic, widespread condition in which the body does not produce or properly use insulin, the hormone needed to transport glucose (sugar) from the blood into the cells of the body for energy. More than 230 million people worldwide are living with the disease and this number is expected to rise to a staggering 350 million within 20 years. It is estimated that nearly 24 million Americans have diabetes, including an estimated 5.7 million who remain undiagnosed. At the same time, about 40 percent of those diagnosed are not achieving the blood sugar control target of HbA1c <7 percent recommended by the ADA. The HbA1c test measures average blood glucose levels over the past two- to three-month period.

About sanofi-aventis

Sanofi-aventis, a leading global pharmaceutical 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).

Forward Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended.  Forward-looking statements are statements that are not historical facts.  These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements regarding future performance.  Forward-looking statements are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans” and similar expressions.  Although sanofi-aventis’ management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements.  These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in sanofi-aventis’ annual report on Form 20-F for the year ended December 31, 2008.  Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.


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