Burlington and Toronto, Ontario, October 3, 2011 – Boehringer Ingelheim Canada and Eli Lilly Canada today announced that Health Canada has approved Trajenta™ (linagliptin), a new oral therapy to improve glycemic control in Canadian adults with type 2 diabetes. Trajenta belongs to a class of prescription medications called dipeptidyl peptidase-4 (DPP-4) inhibitors and is the first of its class to be approved at one dosage strength with no dose adjustment required in patients with mild or moderate renal impairment.[1]

Trajenta can be used as a monotherapy in conjunction with diet and exercise in patients for whom metformin is inappropriate due to contraindications or intolerance, or in combination with other commonly prescribed medications for type 2 diabetes in conjunction with diet and exercise– providing Trajenta with the broadest indication of the DPP-4i class of medications in the Canadian market. Studies show that Trajenta is efficacious with a favourable safety and tolerability profile, reducing hemoglobin A1c levels up to 0.7 per cent compared to placebo.[2],[3] A1c is used as a marker in people with diabetes to determine the efficacy of glucose-lowering therapies.

“Trajenta is an important new option for patients with Type 2 diabetes. Unlike other DPP-4 inhibitors, Trajenta has only five per cent renal excretion, meaning no dose adjustment is needed in adult patients with mild or moderate renal impairment,” says David Lau, M.D., Ph.D., FRCPC, endocrinologist, Chair, Diabetes and Endocrine Research Group, Professor of Medicine, Biochemistry & Molecular Biology, University of Calgary “This is convenient for both patients and physicians, because one dose is the right dose for all adult patients.”

As type 2 diabetes progresses, there is an increasing risk of declining renal function. About 67 per cent of type 2 diabetes patients are at high risk of declining renal function[4],[5] and approximately 30 per cent already have declining renal function.[6] Diabetes patients with declining renal function have an increased risk of serious complications including hypoglycaemic episodes.[7]

Some of the currently available anti-diabetic medications are predominantly cleared through the kidneys before leaving the body. One of the challenges is that as kidney function declines, patients on these medications often have to adjust the dose of their medication, or stop taking it altogether.[8] Metformin and sulfonylrueas, which are two of the most commonly prescribed oral medications in Canada, as well as the DDP-4 inhibitors currently available, are either not indicated for use in patients with compromised renal function, or must be adjusted and monitored carefully as a patient’s renal function declines. [9],[10]

“The approval of Trajenta marks the first regulatory milestone for the Boehringer Ingelheim and Eli Lilly and Company alliance in Canada,” said Dr. Ted Witek, President and CEO, Boehringer Ingelheim Canada. “Together our companies are dedicated to providing type 2 diabetes patients with a new treatment option to improve glycemic control without the concerns of dose adjustments for patients with mild to moderate renal impairment.”

“We are extremely proud to offer a new treatment option that could potentially help the millions of people with Type 2 diabetes in Canada,” said Michael Mason, President and General Manager, Eli Lilly Canada. “Trajenta is the first of what we hope will be many new treatment options this alliance brings to improve patient care in diabetes.”

About Trajenta

Trajenta 5 mg once daily was approved based on a robust clinical development program. Included in the trials were placebo controlled studies evaluating Trajenta as monotherapy in patients for whom metformin therapy is inappropriate, due to intolerability or contraindication [11], and in combination with the commonly prescribed oral anti-diabetic medications metformin and/or sulphonylurea.[12], [13], [14]In two monotherapy studies, Trajenta showed a statistically significant mean difference in A1c from placebo of -0.6 to -0.7 percent.[15],[16] In patients who were not adequately controlled on metformin or metformin plus sulphonylurea, the addition of Trajenta also resulted in a statistically significant mean difference in A1c from placebo of -0.6 per cent.[17],[18] With Trajenta , the A1c reduction achieved with mono, dual and triple therapy at 24 weeks was maintained to 78 weeks of use.[19] Hypoglycemia was rare and weight did not change significantly from baseline.[20],[21]

Treatment with Trajenta also produced significant reductions in fasting plasma glucose (FPG) compared to placebo, when used as monotherapy and in combination with metformin and/or sulfonylurea.[22], [23]Treatment with Trajenta produced significant reductions in two-hour post-prandial glucose (PPG) levels compared with placebo when used in combination with metformin. FPG is used to determine glucose levels in a fasting state (usually upon waking in the morning), and PPG is used to determine glucose levels after meals (usually two hours after eating).

No dose adjustment for Trajenta is required for patients with mild to moderate renal impairment.[24] In controlled studies, change from baseline in body weight did not differ significantly between groups when Trajenta was administered as monotherapy[25], in combination with metformin[26] or in combination with metformin plus sulphonylurea[27]. Patients treated with Trajenta exhibited a significant mean decrease from baseline body weight compared to a significant weight gain in patients administered sulphonylurea (-1.39 kg vs. +1.29 kg p<0.0001).

The safety of Trajenta has been evaluated in 4,687 patients with type 2 diabetes of which 4,040 patients received the target dose of 5 mg.[28] In the pooled analysis of the placebo controlled trials, the overall incidence of adverse events in patients treated with placebo was similar to that seen with linagliptin 5 mg (53.8 per cent versus 55.0 per cent). The most frequently reported adverse reaction was hypoglycemia observed with the triple combination of Trajenta plus metformin plus sulphonylurea (14.7 per cent with Trajenta versus 7.6 per cent with placebo). None of the hypoglycemias were classified as severe.

Trajenta ™ is a trademark used under license by Boehringer Ingelheim (Canada) Ltd.

About Type 2 Diabetes

There are approximately 285 million people with diabetes in the population worldwide[29] and over 9 million Canadians with diabetes or prediabetes.[30] The Canadian Diabetes Association estimates that by 2020, it is expected that 9.9 per cent of the population will be living with diabetes.[31] Type 2 diabetes usually occurs later in life and affects approximately 90 per cent of people with diabetes.[32] The list of complications that diabetes patients face is long. In Canada, diabetes is the single largest cause of blindness and 42 per cent of new kidney dialysis patients in 2004 had diabetes.[33]

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.ca or www.lilly.com .

About Boehringer Ingelheim (Canada) Ltd.

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 42,000 employees.

Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products 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 2010, Boehringer Ingelheim posted net sales of 11.7 billion euro while spending almost 24 per cent of net sales in its largest business segment Prescription Medicines on research and development.

The Canadian headquarters of Boehringer Ingelheim was established in 1972 and the Research and Development Centre located in Laval, Québec, Canada since 1988. Boehringer Ingelheim (Canada) Ltd. is home to more than 700 employees including 160 scientists across the country. For more information please visit www.boehringer-ingelheim.ca

About Eli Lilly Canada Inc.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Indiana, Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs. Eli Lilly Canada, headquartered in Toronto, Ontario, employs close to 500 people across the country. Additional information about Eli Lilly Canada can be found at www.lilly.ca.

CONTACT:

Sara McClelland

Communications

Boehringer Ingelheim (Canada) Ltd.

Email: sara.mcclelland@boehringer-ingelheim.com

Phone: (905) 631-4713

Cell phone: (905) 599-2364

[1] Boehringer Ingelheim (Canada) Ltd. TrajentaTM Product Monograph. 2011; pg16.

[2] Taskinen MR, et al., “Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo controlled study” Diabetes, Obesity and Metabolism, 2011; 13: 65-74

[3] Del Prato S, et al., “Effect of linagliptin monotherapyon glycemic control and markers of B-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial”, Diabetes, Obesity and Metabolism, 2011; 13:193-287

[4] “National Diabetes Fact Sheet”, American Diabetes Association, accessed September 7, 2011, http://www.diabetes.org/diabetes-basics/diabetes-statistics.

[5] “Risk Factors”, Kidney Foundation of Canada, accessed September 7, 2011, http://www.kidney.ca/page.aspx?pid=333

[6] “Diabetes and Kidney Disease”, Canadian Diabetes Association, accessed August 11, http://www.diabetes.ca/diabetes-and-you/living/complications/kidney

[7]Davis TIME, et al., “Determinants of Severe Hypoglycemia Complicating Type 2 Diabetes: Fremantle Diabetes Study”, The Journal of Clinical Endocrinology and Metabolism, 2010;95:2240–47. 2.

[8] Deacon, C.F., “Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review “. Diabetes, Obesity and Metabolism, 2011; 13:7-18, pg12

[9] Sanofi-aventis Canada Inc. Glucophage (metformin) Product Monagraph, 2009; pg4.

[10] Servier Canada Inc. Diamicron Product Monagraph, 2011; pg4

[11] Barnett AH, et al,. “Linagliptin monotherapy improves glycaemic control in type 2 diabetes patients for whom metformin therapy is inappropriate.” Poster 823 presented at the 46th Annual Meeting of the European Association for the Study of Diabetes, Stockholm, Sweden, September 20-24, 2010

[12] Taskinen MR, et al., “Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo controlled study” Diabetes, Obesity and Metabolism, 2011; 13: 65-74

[13] Owens DR, et al,. “Linagliptin improves glycemic control in type 2 diabetes patients inadequately controlled by metformin and sulfonylurea without weight gain and low risk of hypoglycemia.” Poster 548-P presented at the 70th American Diabetes Association Scientific Sessions, Orlando, Florida, June 25-29, 2010

[14] Lewin, AJ, et al,. “Safety and efficacy of linagliptin as add-on therapy to a sulphonylureain inadequately controlled type 2 diabetes.” Poster 821-p presented at the 46th Annual Meeting of the European Association for the Study of Diabetes. Stockholm, Sweden, September 20-24, 2010

[15] Del Prato S, et al., “Effect of linagliptin monotherapyon glycemic control and markers of B-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial”, Diabetes, Obesity and Metabolism, 2011; 13:193-287

[16] Barnett AH, et al,. “Linagliptin monotherapy improves glycaemic control in type 2 diabetes patients for whom metformin therapy is inappropriate.” Poster 823 presented at the 46th Annual Meeting of the European Association for the Study of Diabetes, Stockholm, Sweden, September 20-24, 2010

[17] Taskinen MR, et al., “Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo controlled study” Diabetes, Obesity and Metabolism, 2011; 13: 65-74

[18] Owens DR, et al,. “Linagliptin improves glycemic control in type 2 diabetes patients inadequately controlled by metformin and sulfonylurea without weight gain and low risk of hypoglycemia.” Poster 548-P presented at the 70th American Diabetes Association Scientific Sessions, Orlando, Florida, June 25-29, 2010

[19] Boehringer Ingelheim (Canada) Ltd. TrajentaTM Product Monograph. 2011; pg26.

[20] Taskinen MR, et al., “Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo controlled study” Diabetes, Obesity and Metabolism, 2011; 13: 65-74

[21] Owens DR, et al,. “Linagliptin improves glycemic control in type 2 diabetes patients inadequately controlled by metformin and sulfonylurea without weight gain and low risk of hypoglycemia.” Poster 548-P presented at the 70th American Diabetes Association Scientific Sessions, Orlando, Florida, June 25-29, 2010

[22] Taskinen MR, et al., “Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo controlled study” Diabetes, Obesity and Metabolism, 2011; 13: 65-74

[23] Owens DR, et al,. “Linagliptin improves glycemic control in type 2 diabetes patients inadequately controlled by metformin and sulfonylurea without weight gain and low risk of hypoglycemia.” Poster 548-P presented at the 70th American Diabetes Association Scientific Sessions, Orlando, Florida, June 25-29, 2010

[24] Boehringer Ingelheim (Canada) Ltd. TrajentaTM Product Monograph. 2011; pg16.

[25] Barnett AH, et al,. “Linagliptin monotherapy improves glycaemic control in type 2 diabetes patients for whom metformin therapy is inappropriate.” Poster 823 presented at the 46th Annual Meeting of the European Association for the Study of Diabetes, Stockholm, Sweden, September 20-24, 2010

[26] Taskinen MR, et al., “Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo controlled study” Diabetes, Obesity and Metabolism, 2011; 13: 65-74

[27] Owens DR, et al,. “Linagliptin improves glycemic control in type 2 diabetes patients inadequately controlled by metformin and sulfonylurea without weight gain and low risk of hypoglycemia.” Poster 548-P presented at the 70th American Diabetes Association Scientific Sessions, Orlando, Florida, June 25-29, 2010

[28] Boehringer Ingelheim (Canada) Ltd. TrajentaTM Product Monograph. 2011; pg7.

[29]. “The prevelance and cost of diabetes”, Canadian Diabetes Association, accessed June 10, 2011, http://www.diabetes.ca/diabetes-and-you/what/prevalence/ on: June 2011

[30] “Leading the Fight”, Canadian Diabetes Association, accessed June 10, 2011, http://www.diabetes.ca/about-us/leading-the-fight.

[31] “Leading the Fight”, Canadian Diabetes Association, accessed June 10, 2011, http://www.diabetes.ca/about-us/leading-the-fight.

[32] “Leading the Fight”, Canadian Diabetes Association, accessed June 10, 2011, http://www.diabetes.ca/about-us/leading-the-fight.

[33] “Leading the Fight”, Canadian Diabetes Association, accessed June 10, 2011, http://www.diabetes.ca/about-us/leading-the-fight.