OncologyNew Data From Boehringer Ingelheim's Ongoing Linagliptin Trial Programme Show Promising Safety And Efficacy Results
Study results presented for the first
time in the scientific sessions of this year"s American Diabetes Association
Annual Meeting (ADA) show clinically relevant and statistically significant
reductions in haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG)
levels when linagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, is given
as add-on therapy in Type 2 diabetic patients inadequately controlled with
metformin. Furthermore, these phase II study results show a placebo-like
safety and tolerability profile under these therapeutic conditions. Notably, in
the study no case of hypoglycaemia was recorded with linagliptin
treatment.1
"To date, metformin is the most widely used oral therapy in Type 2
diabetes. However, many patients do not achieve adequate glycaemic
control with metformin alone. As HbA1c and FPG levels are key diagnostic
indicators for effective management of Type 2 diabetes, the significant
efficacy results together with the favourable safety profile shown in this trial
for the investigational drug linagliptin are very encouraging. Based on the
results seen to date, we are very confident that linagliptin, if approved, can
provide additional benefit to patients with Type 2 diabetes," said Dr.
Manfred Haehl, MD, Senior Vice-President Medicine at Boehringer
Ingelheim headquarters. "Type 2 diabetes is a progressive chronic condition
which frequently requires long-term treatment. Physicians treating patients
with Type 2 diabetes need to have a range of treatment options including
combination regimens so they can tailor the therapy to the individual
patient"s need and response. We are now awaiting results from additional
ongoing studies which will further assess the full potential of linagliptin for
the treatment of Type 2 diabetes."
Trial objective and results:
The aim of the 12-week, international, randomised, double-blind placebo-
controlled study was to assess the safety and efficacy profile of linagliptin
as add-on therapy in patients with Type 2 diabetes who were failing to
achieve glycaemic control despite being treated with metformin. Primary
endpoint was the change in HbA1c from baseline to week 12. Out of the 333
randomised patients, 268 patients received double-blind treatment with
linagliptin or placebo. Three doses of linagliptin were investigated in this
study: 1 mg, 5 mg and 10 mg. An open-label arm with 65 patients on
glimepiride was added for descriptive control.
- The addition of linagliptin to metformin treatment for 12 weeks resulted
in clinically relevant and statistically significant reductions in HbA1c and
FPG levels (p-values of less than 0.05%).
- All doses of linagliptin showed superior HbA1c reduction
compared to metformin alone after treatment for 12 weeks (the
placebo-corrected changes from baseline were -0.40% for the
1 mg dose, -0.73% for the 5 mg dose, and -0.67% for the 10 mg
dose). Statistically significant reductions in mean HbA1c levels
with linagliptin 5 mg and 10 mg compared with metformin alone
(both pPlease be advised: This release is from Boehringer Ingelheim Corporate
Headquarters in Germany. Please be aware that there may be national
differences between countries regarding specific medical information,
including licensed uses. Please take account of this when referring to the
information provided in this document. This press release is not intended for
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Notes
About the Boehringer Ingelheim diabetes pipeline
Metabolism is one of Boehringer Ingelheim"s core R&D areas and diabetes
one of the indications at the centre of interest within the company"s global
research network. As a result, Boehringer Ingelheim is pursuing various
modes of action. The company"s most advanced compounds targeting Type
2 diabetes are linagliptin (planned trade name Ondero), an oral once-daily
tablet which belongs to the novel class of dipeptidylpeptidase (DPP-4)
inhibitors and is currently in Phase III development, and a compound in
Phase II which belongs to another class of novel antidiabetics, the sodiumdependent
glucose transporter-2 (SGLT-2) inhibitors.
About Diabetes and Type 2 Diabetes
There are approximately 246 million people with diabetes in the adult
population.2a The International Diabetes Federation estimates the number of
people with diabetes will increase to 380 million people worldwide by
2025.2a Some 3.8 million men and women worldwide were estimated to
have died from diabetes-related causes in the year 2007. This is more than
6% of the total world mortaliy.2b
Type 2 diabetes is the most common type of diabetes accounting for up to
95% of all diabetes cases in the developed world.2a Type 2 diabetes rates
continue to increase and patients continue to be burdened by serious
diabetes-related complications, 2a also reflected in the fact that
approximately 50% of people with diabetes die of cardiovascular disease,
and more than 10% die of renal failure.3 Traditional therapies have
frequently failed to meet the demands of today"s Type 2 diabetes landscape
and new, effective and tolerable treatments are required.
To address this unmet need, Boehringer Ingelheim is committed to
researching and developing new compounds in this disease area.
HbA1c = The erythrocyte haemoglobin become irreversibly glycosylated in
proportion to circulating glucose concentrations, and the resultant product is
commonly referred to as haemoglobin A1c (HbA1c). Because of the half-life
of the erythrocyte, the percentage of haemoglobin represented by HbA1c
provides an index of the average plasma glucose concentration during the
previous two to three months.4
FPG = Fasting plasma glucose is the level of glucose in blood after an
overnight fast.5
References
1. DPP-4 inhibitor linagliptin improves glycaemic control in type 2 diabetes patients when
added to ongoing metformin therapy. Poster No.535-P presented at the 69th American
Diabetes Association Scientific Sessions (ADA), 05-09 June 2009, New Orleans,
U.S.A.
2. International Diabetes Federation. Diabetes Atlas. 3rd edn. Brussels: International
Diabetes Federation, 2006
a. Available at: http://www.eatlas.idf.org/index2983.html. Accessed on 28 April, 2009.
b. Available at http://www.eatlas.idf.org/index3669.html. Accessed on 28 April, 2009.
3. Morrish,N.J. et al.. Mortality and causes of death in the WHO Multinational Study of
Vascular Disease in Diabetes. Diabetologia.2001; 44 Suppl 2: S14-S21
4. Woerle, H.J. et al. Diagnostic and Therapeutic Implications of Relationships Between
Fasting, 2-Hour Postchallenge Plasma Glucose and Hemoglobin A1C
Values. Arch
Intern Med. 2004; 164:1627-1632.
5. American Diabetes Association. Diabetes Research. Available here..
Accessed on: 22 April 2009
Boehringer Ingelheim