New data presented at AASD further demonstrate benefits of Trajenta^® (linagliptin) with efficacy and safety in specific patient populations

Ingelheim, Germany and Indianapolis, US, 7th November 2013 – Boehringer Ingelheim and Eli Lilly and Company announce new data that reinforce the efficacy and tolerability of linagliptin in people with Type 2 Diabetes (T2D) and liver disease, as well as Asian people with T2D aged 65 years or older. The data add to a growing body of clinical evidence supporting the use of linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor from Boehringer Ingelheim (BI) and Eli Lilly and Company, in a broad range of adults with T2D. The data will be announced on Saturday 9th November during the 2013 International Conference on Diabetes and Metabolism & 5th Asian Association for the Study of Diabetes (AASD) Annual Scientific meeting.

Adults with T2D aged 65 years or older and those with pre-existing liver and biliary disease are characterised by limited treatment options. With the rate of T2D rapidly growing in Asia,¹ and the prevalence of T2D and hepatobiliary diseases being high, especially in Asian countries,² effective and safe treatment options are increasingly becoming a priority. Moreover, given the major elimination of linagliptin via the entero-hepatic system, it is particularly important to further characterise the efficacy and safety of linagliptin in T2D patients with liver and biliary complications.

Efficacy and tolerability in people with T2D and previous/current liver and biliary disease
In a pooled analysis of 17 double-blind placebo controlled randomised clinical trials investigating the efficacy and tolerability of linagliptin in people with T2D and self-reported previous/current liver and biliary disease, results showed:

• Linagliptin demonstrated a statistically significant placebo-adjusted reduction in HbA1c of 0.52 and 0.62 percent in patients with- and without hepatobiliary disorders, respectively, from baseline to 24 weeks.³
• Overall incidence of adverse events (AEs) was similar for hepatobiliary (65.1 percent – linagliptin; 68.0 percent – placebo) and non-hepatobiliary patients (56.7 percent – linagliptin; and 62.0 percent - placebo).
• Rates of serious AEs were 7.9 percent vs. 9.9 percent (linagliptin and placebo, respectively) in the hepatobiliary group, and 4.7 percent vs. 6.6 percent, (linagliptin and placebo, respectively) in the non-hepatobiliary group.
• Fewer patients in the linagliptin group experienced drug related AEs than placebo (12 percent vs. 15.3 percent hepatobiliary; 11.6 percent vs. 13.6 percent non-hepatobiliary); and hypoglycaemia was less frequent with linagliptin versus placebo (12.2 percent vs. 19.2 percent hepatobiliary; 11.9 vs. 14.8 non-hepatobiliary).

Efficacy and safety in Asian elderly people with T2D
In a second pooled analysis investigating the efficacy and safety of linagliptin (as monotherapy or in combination with common anti-hyperglycaemic drugs) in Asian people aged 65 years or older with uncontrolled T2D, results showed:

• Linagliptin demonstrated a statistically significant reduction in HbA1c of 0.90 percent, compared to a 0.08 percent reduction with placebo, resulting in a treatment difference of 0.82 percent after 24 weeks.⁴
• Overall incidence of adverse events (AEs) or serious adverse events (SAEs) with linagliptin was similar to placebo (AE 53.6 percent vs 61.9 percent, and SAE 4.5 percent vs. 6.9 percent respectively).
• Drug-related AEs were lower in the linagliptin arm than with placebo (12.6 percent vs. 17.5 percent, respectively); as was the occurrence of investigator defined hypoglycaemia (9.5 percent vs. 18.1 percent, respectively).
• The incidence of symptomatic hypoglycemia events was similar to placebo (1.1 percent in linagliptin vs 1.5 percent in placebo) when patients were not on insulin or sulphonylurea background therapy.
  

  
  
  

  
  

Commenting on the studies, Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim, said: "The effects of treatment on health and safety in specific groups of people with Type 2 Diabetes, such as the elderly and those with liver disease, must be considered when selecting the most appropriate therapy. However, those patients present complications that limit their choice of treatment. The findings that will be presented at AASD support linagliptin’s safety and efficacy in these populations with Type 2 Diabetes, and confirm that linagliptin is an important treatment option."

The U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), Japan Pharmaceuticals and Medical Devices Agency (PMDA) and several other regulatory authorities worldwide have approved linagliptin for the treatment of adults with T2D as monotherapy or in combination with metformin, metformin + sulphonylurea, and as add-on therapy to insulin. With linagliptin, no dose adjustment is required regardless of renal function or hepatic impairment.^5,6

About the studies
Efficacy and tolerability of linagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, in people with Type 2 Diabetes (T2DM) and liver disease: a pooled analysis of 17 randomised placebo-controlled double-blind studies³ (AASD abstract no. 192)Pooled data were analysed from 7009 subjects (621 with a history of hepatobiliary disorders [among whom the most frequent conditions were hepatic steatosis, cholelithiasis, and cholecystitis]) receiving linagliptin (n=418 with hepatobiliary disorder; n=4207 with no hepatobiliary disorder) or placebo (n=203 with hepatobiliary disorder; n=2181 with no hepatobiliary disorder). Almost 40 percent of subjects in each group (hepatobiliary and non-hepatobiliary) were Asian. All studies had a primary outcome measure of change from baseline HbA1c.

Efficacy and safety of linagliptin in Asian patients aged≥65 years: results of a pooled analysis⁴ (AASD abstract no. 170)
Data from placebo-controlled trials evaluating linagliptin (monotherapy or in combination with common anti-diabetes drugs) were pooled. Efficacy data were pooled from 11 trials, comprising 347 Asian adults with T2D (linagliptin n=239; placebo n=108) that included assessments of more than 24 weeks. Safety data were pooled from 15 trials of varying durations, comprising 518 Asian adults with T2D (linagliptin n=358; placebo n=160).

About Linagliptin
Linagliptin (5 mg) is marketed in Europe as Trajenta^® (linagliptin) and in the U.S. as Tradjenta^® (linagliptin), as a once-daily tablet that is used along with diet and exercise to improve glycaemic control in adults with T2D. Linagliptin should not be used in patients with Type 1 Diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine).^5,6

About Diabetes
An estimated 371 million people worldwide have Type 1 and Type 2 Diabetes.⁷ Type 2 Diabetes is the most common type, accounting for an estimated 90 percent of all diabetes cases.⁸ Diabetes is a chronic disease that occurs when the body either does not properly produce, or use, the hormone insulin.⁹

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 three compounds representing several of the largest diabetes 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 140 affiliates and more than 46,000 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.

Social responsibility is a central element of Boehringer Ingelheim's culture. 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 endeavours. In 2012, Boehringer Ingelheim achieved net sales of about €14.7 billion. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% 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 programmes and more – to make lives better.
For more information, visit www.lillydiabetes.com

This press release contains forward-looking statements about linagliptin 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 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.