חברת אוונטיס פרסמה בכנס הסוכרת האירופאי שהתקיים בימים האחרונים במינכן את תוצאות מחקר ה-AT.LANTUS .

מטרת המחקר הייתה לבדוק במציאות של real life שיטות שונות לטיטרציה של אינסולין לנטוס בחולי סוכרת סוג 1 וסוג 2.

המסקנות העיקריות של המחקר הן שבחולי סוכרת סוג 1 , שתי שיטות הטיטרציה שנבדקו הניבו תוצאות טובות מבחינת ירידת ה- A1c עם שיעור דומה של היפוגליקמיות, בעוד שבסוכרת סוג 2 לשיטת הטיטרציה העצמית שבה המטופל עצמו מגדיל את המינון בהתאם לבדיקות הסוכר היומיות היה יתרון בהפחתת ה-A1c , ללא הבדל בשיעור ההיפוגליקמיות.

במחקר השתתפו 7,371 מטופלים, מהם 2,410 עם סוכרת סוג 1  ו-4,961 עם סוכרת סוג 2.

כל המטופלים היו ברמות בסיס של A1c גבוהות מ-7% . היעד שהוצב במחקר היה להשיג רמת סוכר בצום (FBG ) של בין 80-120 מ”ג/ד”ל בסוכרת סוג 1  ומתחת ל-100 מ”ג/ד”ל בחולי סוכרת סוג 2.

בחולי סוכרת סוג 1 המחקר השווה בין אלגוריתם של טיטרציה שבו האינסולין הבאזלי עולה בכמות יח’ קבועה, לטיטרציה שמותאמת לרמות ה-FBG כאשר יעדי המטרה אינם מושגים.

גם בסוכרת סוג 2 הטיטרציה בוצעה בשתי שיטות: שיטה אחת התבססה על ביקורים במרפאה, אשר בהתאם לבדיקות הועלה המינון ב-2-8 יח’ ביום, לאחר שהמינון ההתחלתי היה 10 יח’ לחולים שלפני כן לא טופלו באינסולין.

השיטה השנייה התבססה על טיטרציה עצמית של המטופלים אשר הוסיפו למינון 2 יח’ אינסולין מידי 3 ימים במידה ורמת המטרה של ה-FBG לא הושגה. בנוסף התקיימו ביקורים רגילים במרפאה שבהם בוצעו בדיקות ופיקוח על הטיפול.

התוצאות שהתקבלו כאמור הראו שבסוכרת סוג 1 לא היה הבדל ממשי בין שתי השיטות: בשתיהן הושגה ירידה משמעותית ומובהקת של A1c של 0.68% וירידה ב-FBG של 58 מ”ג/ד”ל. שיעור ההיפוגליקמיות היה דומה: 7.7% לטיטרציה עם מינון עולה קבוע, ו-6.8% בטיטרציה המבוססת על רמת ה-FBG .

נתון מעניין הוא שחולים שטופלו לפני כן באינסולין אחר מסוגים שונים הפחיתו את רמות ה-A1c שלהם ב-1.1% (בחולים שהיו במשטר הזרקה דו יומי) או ב-0.79% (בחולים שהיו במשטר הזרקה תלת יומי).  חולים שהיו במשטר טיפולי אינטנסיבי שכלל שילוב של אינסולין באזלי-בולוסי עם NPH או אינסוליני ביניים אחרים אשר עברו לטיפול בלנטוס חד יומי הפחיתו את ה-A1c שלהם ב-0.63% ואת ה-FBG ב-57 מ”ג/ד”ל.

חולי סוכרת סוג 2  שהשתתפו במחקר,  סבלו מהמחלה במשך 12.3 שנים בממוצע, עם רמות בסיס של 8.9% של A1c , כאשר 72% מהם כבר היו תחת משטר טיפולי של אינסולין. לאחר העברתם לטיפול בלנטוס חלה ירידה של מעל 1% ברמת ה-A1c שלהם. בחולים אלה היה הבדל משמעותי בין הטיטרציה העצמית לטיטרציה שנעשתה במסגרת ביקורי מרפאה.

לא היה הבדל משמעותי בשיעורי ההיפוגליקמיות בין שתי שיטות הטיטרציה (0.9% ו-1.1% ).

הירידה ב- A1c הייתה גדולה יותר בחולים שהועברו לטיפול בלנטוס לאחר שהיו בטיפול פומי בלבד לפני כן – ירידה של 1.48% .

מקור הידיעה: הודעת חברת אוונטיס.

 ניתן לעיין בהודעה המלאה :

Basal Therapy with LANTUS® Improves Glycaemic Control, with Low Risk of Hypoglycaemia, in Patients Failing Prior Insulin Regimens

Once-Daily LANTUS® Shown Safe and Effective in Global Study Of Poorly Controlled Type 1 and Type 2 Diabetes

Strasbourg, France, September 7, 2004 Aventis announced today the results of a worldwide study of more than 7,000 people with diabetes, demonstrating that treatment with the 24-hour basal insulin analogue LANTUS® (insulin glargine [rDNA origin] injection) significantly enhanced glycaemic (blood sugar) control with a low risk of severe hypoglycaemia (low blood sugar). The study population included patients with both type 1 and type 2 diabetes, all of who were failing to reach treatment targets despite use of insulin and/or oral antidiabetic medications.  These findings were presented today in several different sessions at the 40th Annual Meeting of the European Association for the Study of Diabetes in Munich, Germany.

The study, called AT.LANTUS (A Trial comparing LANTUS® Algorithms to achieve Normal blood glucose Targets in patients with Uncontrolled blood Sugar) examined two different algorithms (step-by-step methods) for titrating the dose of LANTUS® in each type of diabetes. (Titration is the process of starting and increasing the dose until a desired result of treatment is achieved—in this case, a predetermined reduction in fasting blood sugar levels.)  In both type 1 and type 2 diabetes, both titration algorithms were used safely to optimize glycaemic control, including significant reductions in A1C and fasting blood sugar levels.  In type 2 diabetes, titration that was self-directed by patients produced significantly greater reductions in A1C and fasting blood sugar than titration performed during physician office visits.

“The AT.LANTUS data, from more than 1,000 investigational sites in 59 countries, confirm that the unique and predictable 24-hour profile of LANTUS® permits proactive titration in real-world clinical practice, with a low risk of severe hypoglycaemia,” said Melanie Davies, MD, Consultant in Diabetes, at the University Hospitals of Leicester and the principle researcher of the study.  “The study included a very large, diverse group of patients with advanced diabetes (for more than 12 years), but all groups showed benefit from LANTUS® therapy regardless of prior treatment options.”

“This extensive study provides important new information on current diabetes treatment patterns around the world, and on the impact of LANTUS® on actual patient care,” said Kim Carroll, vice president, Metabolism at Aventis.  “Its particularly encouraging that patients who switched to LANTUS® from a range of prior insulin regimens—including basal therapy with NPH or premix insulin (conventional insulin use) —achieved significant improvements in A1C and other outcomes.” 

Basal therapy uses a long-acting insulin to control blood sugar throughout the day and night; it may be used in conjunction with oral antidiabetic therapy and shorter-acting insulin at mealtimes. LANTUS® is the first and only once-daily, insulin analogue with no pronounced peak that provides 24-hour basal glycaemic control for adults with type 2 and adults and children 6 years and older with type 1 diabetes.  

A1C, also referred to as glycated hemoglobin or HbA1c, is a measure of blood glucose levels over a two- to three-month period and is the preferred standard blood test for assessing and monitoring glucose control in people with type 1 and type 2 diabetes. The American Diabetes Association recommends that people with diabetes achieve an A1C <7% for optimal diabetes control.  Prominent landmark studies the United Kingdom Prospective Diabetes Study (UKPDS) and the Diabetes Complications and Control Trial (DCCT) have shown that reduction in A1C is associated with a reduced risk for microvascular complications (small blood vessel complications that result in eye, kidney and nerve damage) and macrovascular complications which result in cardiovascular events such as heart attack and stroke).  Other expert organizations, including the International Diabetes Federation, recommend an even tighter goal of A1C <6.5%.

About the AT.LANTUS Trial

AT.LANTUS was a phase IV, multinational, multicenter, randomized, open study.

The full study population consisted of 7,371 patients with poorly controlled diabetes (2,410 with type 1 diabetes and 4,961 with type 2) with baseline A1C level greater than 7% on any diabetes treatment regimen.  Treatment targets were: a fasting blood glucose (FBG) level of 4.4-6.7 mmol/L (80-120 mg/dL) for type 1 patients, and ≤5.5 mmol/L (≤100 mg/dL) in type 2 patients.  Participants were randomized to one of two LANTUS® treatment algorithms for each type of diabetes and followed for 24 weeks.

The Type 1 Diabetes Study compared a fixed-dose increment titration algorithm for basal insulin to one that used variable dose increments for basal insulin according to FBG levels if targets were not reached.

The Type 2 Diabetes Study compared two titration algorithms. One, based on clinic visits, raised the dose of LANTUS® by 2-8 IU increments (with a starting dose of 10 IU for insulin-naïve patients).  The other algorithm, facilitated self-titration by patients, added 2 IU of LANTUS® every 3 days if the target is not reached (with the first dose based on FBG for insulin-naïve patients).  Patients adjusted the dose themselves, and had regular clinic visits under the supervision of an investigator.

Clinical Outcomes

The AT.LANTUS study demonstrated that once-daily LANTUS® basal insulin is effective in improving blood sugar control in a diverse set of people with poorly controlled diabetes at an advanced stage of the disease, with no significant differences between the two sets of algorithms in the incidence of severe hypoglycaemia.

The Type 1 Diabetes Study

For the whole group of patients, both algorithms significantly reduced A1C (-0.68%) and FBG levels (-58 mg/dl), with no clinically significant differences between algorithms.  There was no significant difference between the two treatment algorithms in incidence of severe hypoglycaemia (7.7% for fixed-dose titration and 6.8% for variable-dose titration).

·        Overall, among patients previously treated with premix insulin, the switch to once-daily LANTUS® plus prandial (mealtime) insulin decreased A1C levels by 1.10% (if patients had been treated with <2 injections a day) to 0.79%  (for patients on > 3 injections a day).

·        Among patients previously treated with an intensified basal-bolus regimen with NPH (Neutral Protamine Hagedorn) or other intermediate-acting insulin as their basal insulin, the switch to once-daily LANTUS® as basal insulin was associated for the whole group with a significant decrease in A1C (-0.63%) and FBG (-57 mg/dl).

The Type 2 Diabetes Study

AT.LANTUS represents a very large prospective randomized study of glycemic management in type 2 diabetes.  Participants had type 2 diabetes of 12.3 years average duration, with an average A1C of 8.9% at baseline; 72% were already on some form of insulin therapy before starting LANTUS®.  By studys end, LANTUS®-treated patients had statistically significant decreases in A1C (>1%) and FBG from baseline values.

 · Patients who self-titrated LANTUS® showed significant additional reductions in A1C and FBG, compared to patients whose titration was managed during clinic visits.

 · There was no significant difference between the two treatment algorithms in incidence of severe hypoglycaemia (0.9% versus 1.1%).

 · Among patients previously treated with twice-daily premix insulin, A1C levels significantly decreased after treatment with once-daily LANTUS® (alone or with prandial insulin and/or oral diabetes medications), with a very low incidence of severe hypoglycaemia (2.2% or less).

·        Among patients previously treated only with once- or twice-daily NPH, A1C levels significantly decreased after treatment with once-daily LANTUS® alone (by 0.8% and 0.9% for the first and second algorithms, respectively). 

      Among patients poorly controlled on oral antidiabetic medication at the start of the study, the addition of LANTUS® to one or more oral medications was associated with a reduction of at least 1.48% in A1C. 

About LANTUS® (insulin glargine [rDNA origin] injection)

LANTUSÒ (insulin glargine [rDNA origin] injection) 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 hyperglycaemia and for adult and pediatric patients (6 years of age and older) with type 1 diabetes mellitus.  LANTUSÒ demonstrates a consistent slow, prolonged absorption and a relatively constant concentration/time profile over 24 hours.

 
 
LANTUS® must not be diluted or mixed with any other
 
insulin or solution.  If mixed or diluted, the solution may become
cloudy,  and the onset of action/time to peak effect may be altered in an unpredictable manner. 
The adverse events commonly associated with LANTUS®
 
include the following: hypoglycaemia, lipodystrophy, skin reactions (such as injection-site reaction, pruritus, rash), and allergic reactions.  Hypoglycaemia is the most common adverse effect of insulins, including LANTUS®.  For additional information, please visit:
 
www.lantus.com.

About Apidra®

In April 2004, the U.S. Food and Drug Administration approved Apidra® (insulin glulisine [rDNA origin] injection), a rapid acting insulin analogue, for the treatment of adult patients with diabetes mellitus for the control of hyperglycaemia. On June 7th, 2004, the Committee for Medicinal Products for Human Use (CHMP), the scientific body of the European Medicines Evaluation Agency (EMEA), issued a positive opinion for Apidra® for the treatment of type 1 and type 2 diabetes mellitus. In combination with LANTUS®, Apidra® provides a synergistic approach to total glucose control.

Hypoglycemia is the most common adverse effect of insulin therapy, including Apidra®. Adverse events sometimes associated with human insulin therapy include allergic reactions, injection site reaction, lipodystrophy, pruritus and rash.

About Amaryl®

Amaryl® retains a favorable safety profile—the incidence of hypoglycemia with Amaryl® as documented by blood glucose values<60mg/dL, ranged from 0.9% to 1.7%.  Other most common adverse reactions (>1%) (n=746) include dizziness (1.7%) asthenia (1.6%), headache (1.5%), and nausea (1.1%).

As with all sulfonylureas, severe hypoglycemia may occur.

About Aventis Diabetes Products

LANTUS® (insulin glargine [rDNA origin] injection), which was launched in Germany in 2000, in the U.S. in 2001, in the UK and Ireland in 2002, and in France and Japan and over 40 other countries in 2003, is expected to become the flagship of the Aventis diabetes portfolio. This novel basal insulin analogue with no pronounced peak, which provides 24-hour basal glucose control while being administered just once per day, generated sales of € 487 million in 2003. In addition to LANTUS®, Aventis also offers Amaryl® (glimepiride tablets), a once-daily oral sulfonylurea as an adjuvant to diet and exercise that lowers blood glucose levels in type 2 diabetes. Amaryl® generated global sales of € 596 million in 2003. The Insuman® family of insulins generated sales of € 176 million globally in 2003. 

Pipeline products include Exuberaâ (inhaled insulin), submitted to the EMEA in early 2004, which is being developed in partnership with Pfizer, Inc.  In June 2003 Aventis signed a licensing agreement with Zealand Pharma A/S for the development and worldwide commercialization of AVE-0010, a GLP-1 (glucagon-like peptide-1) receptor agonist of the exendin class currently in phase I/II.

Full prescribing information is available by visiting the Aventis Pharmaceuticals U.S. Web site at http://www.aventis-us.com. Also available at this U.S. website are copies of this release or any recent release.

 About Aventis

Aventis is dedicated to treating and preventing disease by discovering and developing innovative prescription drugs and human vaccines. In 2003, Aventis generated sales of €16.79 billion, invested €2.86 billion in research and development, and employed approximately 69,000 people in its core business. Aventis corporate headquarters are in Strasbourg, France. For more information, please visit: www.aventis.com