New data for once-daily linagliptin show durable efficacy over two years

Lisbon, Portugal, 16 September, 2011 – Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) today announced results of a 102 week Phase III study for linagliptin (trade name Trajenta® in Europe), which show meaningful and durable reductions in blood glucose for adults with type 2 diabetes (T2D). In the two-year study presented today at the 47^th Annual Meeting of the European Association for the Study of Diabetes (EASD), the DPP-4 inhibitor linagliptin showed a favourable safety profile and lowered HbA1c levels by 0.8% over the long term¹ in those patients treated with linagliptin for the full study period.

"These results show that the efficacy achieved by linagliptin is reliable and meaningful in a clinical setting, but also that it is durable over the long term. This is especially important in chronic conditions such as type 2 diabetes," commented Prof. David Owens, Clinical Professor of the Department of Medicine, Cardiff University School of Medicine, Wales, UK.

The data from these patients demonstrate the efficacy and tolerability of linagliptin as mono-, dual- (plus metformin or initial combination with pioglitazone) or triple (plus metformin and sulphonylurea) oral therapy over a period of 102 weeks. Reductions in HbA1c of 0.8% after 24 weeks of blinded treatment were seen to be durable over the additional 78 weeks. Overall, the rate of hypoglycaemic events was low and body weight remained unchanged.²

An additional 12-week study also indicated the efficacy and tolerability of linagliptin as add-on therapy to metformin. In the trial, type 2 diabetes patients uncontrolled with metformin twice daily (≥1500mg/day) were randomised either to linagliptin 2.5mg twice daily (to enable integration with metformin twice daily dosing regimen during this 12-week-study) or linagliptin 5mg approved dose once daily. Results showed comparable placebo-adjusted HbA1c reductions of -0.74% and 0.8% respectively (from a mean baseline HbA1c of 8.0%, p<0.0001). ²

"Linagliptin is a new treatment that is primarily excreted unmetabolised via the bile and gut, and so delivers reliable HbA1c reductions at one dosage strength for all patients, even for those with declining hepatic or renal function," said Prof. Anthony Barnett, Consultant Physician, Heart of England NHS Foundation Trust and Emeritus Professor of Medicine, University of Birmingham, UK. "One dosage strength for all patients will help make the process of prescribing easier and more straightforward for physicians."

The data presented at EASD demonstrate meaningful efficacy of linagliptin with a good safety and tolerability profile across the full spectrum of type 2 diabetes, from newly diagnosed patients to those with severe renal impairment.³

Highlights of Linagliptin Clinical Studies Presented at EASD

• Long-term safety and efficacy of the DPP-4 inhibitor linagliptin: data from a large 2-year study in subjects with type 2 diabetes mellitus ¹
  
  The aim of this two-year study was to assess the long term efficacy and safety profile of linagliptin monotherapy , dual-therapy (plus metformin or in initial combination with pioglitazone) or triple-therapy (plus metformin + sulphonylurea) to treat T2D in those patients who have not achieved adequate glycaemic control (N=2121). Patients who previously completed one of four double-blind, placebo-controlled 24-week Phase III studies were enrolled in this open-label single-arm 78-week label extension trial.
  • Significant reductions in HbA1c achieved with linagliptin after 24 weeks' blinded treatment (-0.8%) were sustained over the further 78-wks open label extension (2-yr change vs. baseline of -0.8%).
  • Patients who were initially randomised to placebo before switching to linagliptin therapy at week 24 achieved a further reduction of 0.5% after the extension period. Treatment with linagliptin continued to be well-tolerated during the extension period.
  • The overall incidence of hypoglycaemic events during the extension period was similar for subjects continuing with linagliptin (14.6%) and those switching from placebo (13.6%).
  • Approximately one-third of subjects in each group were receiving background metformin plus sulphonylurea therapy. Hypoglycaemic events were most frequent in these subjects receiving triple therapy including sulphonylurea.
    
• Efficacy and safety of 5mg daily dosing regimens with linagliptin in adult patients with type 2 diabetes inadequately controlled on metformin ²
  
  The aim of this 12 week study was to assess the safety and efficacy of linagliptin 5mg once-daily and 2.5mg twice-daily when given in addition to metformin twice daily (≥1500mg/day) (N=491).
  • Linagliptin 2.5mg bid (twice per day) and 5mg qd (once per day) significantly reduced HbA1c (placebo-adjusted changes of -0.74% and -0.80%, both p<0.0001).
  • Efficacy was comparable for the two linagliptin regimens with a difference in HbA1c (0.06%) that was within the predefined noninferiority margin.
  • Rates of adverse events (AEs) were similar with linagliptin 2.5 mg bid, 5 mg qd and placebo (43.0%, 34.8% and 38.6%, respectively). Most AEs were mild-to-moderate in intensity and few were deemed related to study medication in any group.
    
• Long term efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment ³
  The aim of this 52-week, randomised, double-blind, placebo-controlled trial was to evaluate the efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment.
  • The adjusted mean change in HbA1c from baseline at week 52 was -0.72% (95% CI -1.03, -0.41; p<0.0001), confirming the superiority of linagliptin over placebo as demonstrated at week 12.
  • HbA1c values for the 12-52 week period showed that reductions were maintained throughout the study.
  • Rates for any adverse event (AE) and serious AEs were similar with linagliptin (94.1% and 36.8%, respectively) and PBO (92.3% and 41.5%).
  • Renal function remained stable throughout the study in both treatment arms, and numbers of cardiovascular deaths in this high-risk population were similarly low (linagliptin, n=2 [2.9%]; PBO, n=3 [4.6%]).
    
• Linagliptin improves glycaemic control independently of diabetes duration and insulin resistance in patients with type 2 diabetes ⁴
  
  The aim of this pooled analysis of three randomised, double-blinded, placebo-controlled, Phase III trials was to examine the safety and efficacy of linagliptin monotherapy, as add-on to metformin, or as add-on to metformin + sulphonylurea in patients with type 2 diabetes (N=2258).
• • Treatment with linagliptin provided clinically meaningful HbA1c reductions of -0.7% in patients with T2D independent of the diabetes duration and the degree of insulin resistance (IR), with an overall incidence of adverse events comparable to placebo.
  • Mean disease duration was up to 1 year in 13% of patients, > 1-5 years in 30% of patients, and >5 years in 57% of patients.
  • The overall hypoglycaemic event rate with linagliptin as monotherapy and add-on to metformin therapy was very low (≤1.0%).

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 about 12.6 billion euro while spending almost 24 percent of net sales in its largest business segment Prescription Medicines on research and development.

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 organizations. 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
For more than 85 years, Lilly has been a worldwide leader in pioneering industry-leading solutions to support people living with and treating diabetes. Lilly introduced the world's first commercial insulin in 1923, and remains at the forefront of medical and delivery device innovation to manage diabetes. Lilly is also committed to providing solutions beyond therapy - practical tools, education, and support programs to help overcome barriers to success along the diabetes journey. At Lilly, the journeys of each person living with or treating diabetes inspire ours. 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 commercialization. There is no guarantee that future study results and patient experience will be consistent with study findings to date or that linagliptin will 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.