Boehringer Ingelheim, Lilly present post-hoc analysis data from linagliptin clinical trials at EASD 2013

Eli Lilly and CompanySep 24 2013

Boehringer Ingelheim and Eli Lilly and Company (Lilly; NYSE: LLY) today announced results from two post-hoc, pooled analyses of data from placebo-controlled clinical trials, which examined the safety of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin in adults with type 2 diabetes (T2D). These data were presented at the 49^th Annual Meeting of the European Association for the Study of Diabetes (EASD).

Linagliptin, which is marketed as TRADJENTA^® (linagliptin) tablets in the U.S., is a once-daily, 5 mg tablet used along with diet and exercise to improve glycemic control in adults with type 2 diabetes. 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). TRADJENTA has not been studied in patients with a history of pancreatitis, and it is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using TRADJENTA.

General safety analysis 
Findings from a pooled, post-hoc analysis of safety data from 22 linagliptin clinical trials with 7,400 adults with T2D (4,810 received linagliptin, 2,590 received placebo) included the following:

• The hypoglycemic incidence rate for linagliptin compared with placebo was 11.5 percent vs. 14 percent, respectively
• Overall incidence of adverse events (AE) or serious adverse events (SAE) with linagliptin was similar to placebo (AE 56.5 percent versus 61.2 percent, and SAE 4.8 percent versus 6.3 percent, respectively)

"Drug safety is an important consideration in the selection of appropriate treatments for adults with type 2 diabetes, as different populations often may have drug contraindications and require dose adjustments to help manage their disease," said Prof. Nikolaus Marx, Professor of Medicine and Cardiology, University Hospital of Aachen, Germany. "The results presented today examine the safety profile of linagliptin."

Renal safety data in the elderly 
Results from another post-hoc analysis evaluated pooled data from seven randomized, placebo-controlled phase III clinical trials including 1,293 adults with T2D who were 65 years or older showed:

• Overall renal function, as assessed by estimated glomerular filtration rate (eGFR), was not significantly altered by treatment with linagliptin from baseline to week 24, compared with placebo (adjusted mean ± SE eGFR of −1.8 ± 0.7 mL/min for linagliptin vs. −1.1 ± 0.9 mL/min for placebo). The majority of patients in the linagliptin group had mild renal impairment with similar proportions of mild, moderate and severe renal impairment found in the placebo group.
• Renal and urinary AEs were experienced by 5.5 percent and 4.3 percent of linagliptin and placebo patients, respectively
• Incidence of investigator-defined hypoglycemia was lower in patients who received linagliptin compared with placebo (21.3 percent versus 24.7 percent), with most events occurring in trials that included a sulfonylurea or basal insulin as background therapy
• Acute renal failure occurred in 0.5 percent and 0.2 percent of linagliptin and placebo patients, respectively

"The results from these pooled analyses continued to demonstrate that linagliptin is a treatment option for a wide range of adults with type 2 diabetes, including the elderly and those with renal impairment," said Christophe Arbet-Engels, MD, PhD, vice president, metabolic clinical development and medical affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "These findings provide healthcare providers with additional information they may need to help manage the increasing number of adults with type 2 diabetes they work with every day."

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