New linagliptin Phase III data demonstrate significant reductions in blood glucose with no additional risk of hypoglycaemia when combined with insulin in patients with type 2 diabetes

INGELHEIM, Germany & INDIANAPOLIS--(BUSINESS WIRE)--Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) presented results from a randomised Phase III clinical trial and a post-hoc analysis for linagliptin at ADA. The results showed that adults with type 2 diabetes (T2D) treated with linagliptin in combination with certain other diabetes therapies achieved clinically meaningful blood glucose control.^1,2Linagliptin is a once-daily tablet that is used along with diet and exercise to improve glycaemic control in adults with T2D.^3,4

“Type 2 diabetes is a chronic, progressive condition and glycaemic control becomes harder to achieve over the long term”

“Type 2 diabetes is a chronic, progressive condition and glycaemic control becomes harder to achieve over the long term,” said Professor Baptist Gallwitz, Eberhard-Karls-University, Germany. “Metformin is a standard first-line treatment and many patients eventually require insulin to maintain glycaemic targets. Taken together, these two studies show that linagliptin can provide meaningful glycaemic control both in the early and later stages of the disease. In addition linagliptin is the only diabetes treatment to be approved at one dosage strength meaning physicians can be confident their patients are always on the right dose.”

Results of the one Phase III study presented (Poster No. 999-P) showed that linagliptin was effective as an add-on therapy to basal insulin alone or in combination with metformin and/or pioglitazone in reducing blood glucose levels in adult patients with T2D, when compared to placebo as an add-on to these background therapies. Linagliptin demonstrated a placebo-adjusted reduction in HbA1c of 0.65% (p<0.0001) from a baseline HbA1c of 8.3% at 24 weeks without weight gain or additional risk of hypoglycaemia.¹HbA1c is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months.

A post-hoc analysis from a second Phase III trial (Poster No. 1044-P) found that in hyperglycaemic patients on a background of metformin randomised to add linagliptin or glimepiride, a greater proportion of patients taking linagliptin achieved target HbA1c <7% without weight gain and/or hypoglycaemia than those taking glimepiride after 104 weeks (linagliptin 54% versus glimepiride 23%)² while comparably improving blood glucose levels.²

Linagliptin (5 mg, once-daily) is marketed in the U.S. as Tradjenta™ (linagliptin), in Europe as Trajenta™ (linagliptin), and in other global markets 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). Linagliptin is not approved for use in combination with insulin. With linagliptin, no dose adjustment is required regardless of declining renal function or hepatic impairment.^3,4

Efficacy and Safety of Linagliptin as Add-On Therapy to Basal Insulin in Patients with Type 2 Diabetes

This 52-week, multicentre, randomised, placebo-controlled Phase III study evaluated the efficacy and safety of linagliptin as an add-on therapy to basal insulin alone, or in combination with metformin and/or pioglitazone in adult patients with T2D. The study included 1,261 patients who had inadequate glycaemic control with a stable dose of basal insulin (i.e., insulin glargine, insulin detemir or NPH insulin)¹with or without metformin and/or pioglitazone. Patients were randomised to receive either 5 mg of linagliptin or placebo once daily. The primary efficacy endpoint was the mean change in HbA1c from baseline to week 24, during which time the basal insulin and metformin and/or pioglitazone doses remained stable.¹

At 24 weeks, linagliptin achieved a significant placebo-adjusted mean change in HbA1c from baseline of -0.65%.¹ The overall frequency of adverse events (linagliptin 71.8%, placebo 72.5%) and hypoglycaemia (linagliptin 25.7%, placebo, 27.3%) were similar in both groups.¹ In addition, body weight did not significantly change from the baseline (-0.17 kg ± 0.11 kg versus +0.13 kg ± 0.12 kg; p=0.07) in the linagliptin and placebo groups, respectively.¹

Linagliptin is More Effective than Glimepiride at Achieving a Composite Outcome of A1C Target with No Hypoglycemia and No Weight Gain over Two Years in Mildly Hyperglycemic Type 2 Diabetes Patients on Metformin

A post-hoc analysis of a 104-week study assessed the proportion of adult patients with T2D treated with linagliptin versus glimepiride on a background of metformin who achieved a glycaemic target of HbA1c <7% without weight gain (defined as <1 kg increase in body weight versus baseline) and without hypoglycaemia (defined event per protocol).²

Analyses were based on a per-protocol population on treatment after two years without the use of rescue medication (according to fasting plasma glucose and HbA1c thresholds). A total of 504 patients were evaluable (233 linagliptin; 271 glimepiride). Baseline HbA1c levels were similar in the two groups (linagliptin, 7.2% and glimepiride, 7.3%). After 104 weeks, linagliptin and glimepiride each had a mean HbA1c reduction from baseline of -0.6% and 76% of patients achieved HbA1c <7% in both groups.6% versus 22% experienced hypoglycaemia and 22% vs. 55% experienced weight gain in the linagliptin versus glimepiride arms. Consequently, a significantly higher proportion of patients in the linagliptin group compared with the glimepiride group achieved the composite endpoint (weight gain and/or hypoglycaemia 54% vs. 23% respectively). The odds ratio for achieving the composite endpoint was 4 times higher with linagliptin (p<0.0001).²

About Diabetes

An estimated 366 million people worldwide have type 1 and type 2 diabetes.⁵ Type 2 diabetes is the most common type, accounting for an estimated 90 to 95% of all diabetes cases.⁶ Diabetes is a chronic disease that occurs when the body either does not properly produce, or use, the hormone insulin.⁷

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 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.

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¹ References Yki-Jarvinen H, Duran-Garcia S, Pinnetti S, et al. Efficacy and Safety of Linagliptin as Add-On Therapy to Basal Insulin in Patients With Type 2 Diabetes. Poster No. 999-P. Presented at the American Diabetes Association^® 72^nd Scientific Sessions. June 8-12, Philadelphia, PA.
²Gallwitz B, Rosenstock J, et al. Linagliptin is More Effective than Glimepiride at Achieving a Composite Outcome of A1C Target with No Hypoglycemia and No Weight Gain over two Years in Mildly Hyperglycemic Type 2 Diabetes Patients on Metformin. Poster No. 1044-P. Presented at the American Diabetes Association’s (ADA’s) 72^nd Scientific Sessions^®. June 8-12, Philadelphia, PA.
³ 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
⁴Tradjenta™ (linagliptin) tablets. Highlights of Prescribing Information. Initial U.S. Approval: 2011.
⁵ International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: The Global Burden. 2011. http://www.idf.org/diabetesatlas/5e/the-global-burden. Accessed on: April 11, 2012.
⁶Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
⁷International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: What is Diabetes? http://www.idf.org/diabetesatlas/5e/what-is-diabetes. Accessed on: April 11, 2012.