New Data From Boehringer Ingelheim's Ongoing Linagliptin Trial Programme Show Promising Safety and Efficacy Results

Ingelheim, Germany (ots/PRNewswire) -

- Results From Linagliptin Study in Type 2 Diabetes Patients Who
Were Inadequately Controlled on Metformin Therapy Alone, Presented at
Major Diabetes Meeting

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 p greater than 0.001) were observed already from week four
onwards.
- In addition, all linagliptin doses showed significant reductions
in FPG levels compared with metformin alone (the placebo-corrected
mean changes from baseline were -19.2 mg/dL for 1 mg, -34.7 mg/dL
for 5 mg, and -29.0 mg/dL for 10 mg).
- In the open-label comparator arm, the placebo-corrected mean
change from baseline in HbA1c was -0.90%.
- The predefined efficacy criterion of more than 80% DPP-4 inhibition in
more than 80% of patients was reached with the 5 mg and 10 mg
linagliptin doses, but not with the 1 mg dose, which fully supports the
5mg dose as optimal dosage.
- HbA1c reductions of greater than or equal to 0.5% were achieved in 44%
to 53% of patients on linagliptin, but only in 13% of the patients
receiving metformin alone.
- Linagliptin had a placebo-like safety/tolerability profile.
The incidence of adverse events was similar in all treatment
groups. No dose relationship of adverse event was observed
- No cases of hypoglycaemia were recorded in the linagliptin groups,
whereas three hypoglycaemic episodes were reported in the
glimepiride group.

INGELHEIM, Germany, June 6 /PRNewswire/ --

Linagliptin is the most advanced compound for the treatment of
Type 2 diabetes within Boehringer Ingelheim's diabetes portfolio.
Linagliptin belongs to the class of DPP-4 inhibitors and is being
developed as an oral once-daily tablet. It is currently in phase III
clinical development.

Please 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 distribution within the U.S.A.

Notes to Editor:

About the Boehringer Ingelheim diabetes pipeline

Metabolism is one of Boehringer Ingelheim's core R&D areas and
diabetes is 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
sodium-dependent glucosetransporter-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 mortality.(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 becomes 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)

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading
pharmaceutical companies. Headquartered in Ingelheim, Germany, it
operates globally with 138 affiliates in 47 countries and 41,300
employees. Since it was founded in 1885, the independent,
family-owned company has been committed to researching, developing,
manufacturing and marketing novel products of high therapeutic value
for human and veterinary medicine.

In 2008, Boehringer Ingelheim posted net sales of 11.6 billion
euro while spending one fifth of net sales in its largest business
segment Prescription Medicines on research and development.

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, 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 at:
http://www.diabetes.org/diabetes-research/summaries/tirosh-plasma-
glucose.jsp. Accessed on: 22 April 2009

INGELHEIM, Germany, June 6 /PRNewswire/ --

For more information please visit
http://www.boehringer-ingelheim.com

ots Originaltext: Boehringer Ingelheim
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Contact:
Contact: Ursula Bardon, Corporate Division Communications, Boehringer
Ingelheim GmbH, 55216 Ingelheim/Germany, Phone: +49-6132-77-2622,
Fax: +49-6132-72-2622, E-mail: press@boehringer-ingelheim.com