Jentadueto® (linagliptin/metformin hydrochloride) tablets receive approval for the treatment of adults with Type 2 Diabetes in Europe

New treatment will provide a single tablet option for adults who need to reduce their blood sugar

For Non-U.S. and Non-UK Media

Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) received Marketing Authorisation from the European Commission for Jentadueto^® which combines the DPP-4 inhibitor, linagliptin and metformin in a single tablet. ¹ Linagliptin/metformin hydrochloride (HCl) will provide a new, single-tablet treatment option, taken twice-daily, for adults with Type 2 Diabetes.¹

“We’re delighted that linagliptin/metformin hydrochloride (HCl) will soon be available across Europe to help people with Type 2 Diabetes,” said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “Many patients need more than one treatment to adequately manage their diabetes. Linagliptin/metformin hydrochloride (HCl) offers a simplified, single tablet dosing option, to improve glycaemic control and with a favourable side effect profile.”

The European Commission has approved linagliptin/metformin hydrochloride (HCl) for use alongside diet and exercise to improve glycaemic control in adults with Type 2 Diabetes who are inadequately controlled on their maximal tolerated dose of metformin alone, metformin and a sulphonylurea, or those already being treated with the combination of linagliptin and metformin.¹ It may also be used with a sulphonylurea.

In clinical trials, statistically significant, placebo-corrected mean reductions in haemoglobin A_1c (HbA_1c or A_1C ) levels of -1.7 percent were observed in patients with inadequate glycaemic control when the maximum dose of 2.5 mg linagliptin/1,000 mg metformin HCI was administered twice daily.^1.2 HbA_1c is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months. In clinical studies, linagliptin/metformin HCl did not cause any significant change in body weight, and can be used alone or in combination with a sulphonylurea, a commonly prescribed medication for Type 2 Diabetes.¹

Linagliptin/Metformin HCl Clinical Trials

In a 24-week, randomised, double-blind, placebo controlled study evaluating 791 patients with Type 2 Diabetes and inadequate glycaemic control with diet and exercise, 2.5 mg linagliptin/1,000 mg metformin HCl twice daily demonstrated the following:¹

• Statistically significant, placebo-corrected mean HbA_1c reductions of -1.7 percent
• Statistically significant reductions in fasting plasma glucose (FPG) of -60 mg/dL. FPG is used to determine glucose levels in a fasting state (usually upon waking in the morning)

The approval of linagliptin/metformin HCl tablets was based on clinical trials that evaluated linagliptin and metformin as separate tablets. Bioequivalence of linagliptin/metformin HCl was demonstrated in a previous study, with co-administered linagliptin and metformin tablets in healthy subjects with Type 2 Diabetes.^1,2

In clinical studies, adverse reactions were uncommon. Gastrointestinal disorders occurred most frequently during initiation therapy with linagliptin/metformin HCl or metformin HCl and tended to resolve spontaneously. A comparable rate of diarrhoea was reported with linagliptin/metformin HCl treatment versus metformin plus placebo.² Due to the impact of background therapy, hypoglycaemia was more commonly reported in patients treated with the combination of linagliptin/metformin HCl and sulphonylurea compared with those treated with the combination of placebo, metformin and sulphonylurea.¹

Linagliptin (5 mg, once-daily) is marketed as Trajenta^® across Europe and Canada, as Tradjenta^® in the US, and Trazenta^® in Japan, as well as in additional markets.

About Linagliptin/Metformin HCl

Linagliptin/metformin HCl is not intended to be used in patients with Type 1 Diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine).^1,3

The use of linagliptin/metformin HCl in combination with insulin has not been adequately studied.^1,3

Linagliptin/metformin HCl will be made available in the following twice-daily doses in Europe: 2.5 mg linagliptin/850 mg metformin tablets and 2.5 mg linagliptin/1,000 mg metformin tablets.¹

About Linagliptin

Linagliptin is an inhibitor of the enzyme DPP-4 (dipeptidyl peptidase-4) which is involved in the inactivation of the incretin hormones GLP-1 and GIP (glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide). Linagliptin glucose-dependently increases insulin secretion and lowers glucagon secretion thus resulting in an overall improvement in the glucose homoeostasis.¹

Linagliptin (5 mg, once-daily) is marketed as Trajenta^® across Europe and Canada, as Tradjenta^® in the US, and Trazenta^® in Japan, as well as in additional markets.^4,5

Linagliptin is a prescription medicine that is used along with diet and exercise to lower blood glucose in adults with Type 2 Diabetes.^4,5 Linagliptin is not for people with Type 1 Diabetes or for people with diabetic ketoacidosis (increased ketones in the blood or urine). ^4,5 It is not known if linagliptin is safe and effective when used with insulin.⁵

About Diabetes

An estimated 366 million people worldwide have Type 1 and Type 2 Diabetes.⁶ Type 2 Diabetes is the most common type, accounting for an estimated 85 to 95% of all diabetes cases.⁷ Diabetes is a chronic disease that occurs when the body either does not properly produce, or use, the hormone insulin.⁸

Boehringer Ingelheim and Eli Lilly and Company

In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in the field of diabetes that centres on four pipeline compounds representing several of the largest treatment classes. This alliance leverages the companies’ strengths as two of the world’s leading pharmaceutical companies, combining Boehringer Ingelheim’s solid track record of research-driven innovation and Lilly’s innovative research, experience, and pioneering history in diabetes. By joining forces, the companies demonstrate commitment in the care of patients with diabetes and stand together to focus on patient needs. Find out more about the alliance at www.boehringer-ingelheim.com or www.lilly.com .

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 145 affiliates and more than 44,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2011, Boehringer Ingelheim achieved net sales of about 13.2 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales.

For more information please visit www.boehringer-ingelheim.com

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organisations. Headquartered in Indianapolis, IN, Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com .

About Lilly Diabetes

Lilly has been a global leader in diabetes care since 1923, when we introduced the world’s first commercial insulin. Today we work to meet the diverse needs of people with diabetes through research and collaboration, a broad and growing product portfolio and a continued commitment to providing real solutions - from medicines to support programs and more - to make lives better.

For more information, visit www.lillydiabetes.com .

This press release contains forward-looking statements about linagliptin and linagliptin/metformin HCl tablets for the treatment of Type 2 Diabetes. It reflects Lilly's current beliefs; however, as with any such undertaking, there are substantial risks and uncertainties in the process of drug development and commercialisation. There is no guarantee that future study results and patient experience will be consistent with study findings to date or that linagliptin and linagliptin/metformin HCl will prove to be commercially successful. For further discussion of these and other risks and uncertainties, please see Lilly's latest Forms 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

No. No. No.

1. Jentadueto^® (linagliptin/metformin HCI) tablets. EMA Summary of Product Characteristics. 2012
2. Haak T, Meinicke T, Jones R, Weber S, Eynatten M von, Woerle HJ Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomised, double-blind, placebo-controlled study. Diabetes Obesity and Metabolism, Accepted manuscript online: 22 FEB 2012, doi: 10.1111/j.1463-1326.2012.01590.x Diabetes Obes Metab 14 (6) , 565-574 (2012)
3. Jentadueto^TM (linagliptin/metformin HCI) tablets. Highlights of Prescribing Information. Initial US Approval: 2012
4. Trajenta^® (linagliptin) tablets. EMA Summary of Product Characteristics. Approval 25 September 2011. www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002110/WC500115745.pdf
5. Tradjenta^TM (linagliptin) tablets. Highlights of Prescribing Information. Initial U.S. Approval: 2011.
6. International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: The Global Burden
   http://www.idf.org/diabetesatlas/5e/the-global-burden . Accessed on: June 21, 2012.
7. International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: Diabetes
   http://www.idf.org/diabetesatlas/5e/diabetes . Accessed on: June 21, 2012.
8. International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: What is Diabetes? http://www.idf.org/diabetesatlas/5e/what-is-diabetes . Accessed on: June 21, 2012.

Contact:

Boehringer Ingelheim GmbH
Ute E Schmidt
Email: press@boehringer-ingelheim.com
Phone: +49 (6132) 77-97296
or
Lilly Diabetes
Tammy Hull
Communications Manager
Email: hullta@lilly.com
Phone: +1 (317) 651-9116