June 25, 2013
/PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) today announced results from a new pooled analysis of phase III data for the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin. The post-hoc meta-analysis, presented at the American Diabetes Association
73rd Scientific Sessions
, compared the incidence of cardiovascular (CV) events with linagliptin for the treatment of adults with type 2 diabetes (T2D) with the incidence of CV events for a number of comparators (placebo, glimepiride and voglibose).
People with T2D have a significantly elevated risk for heart attack, stroke and other CV events, compared with the general population. A second abstract published in the ADA's abstract book for the conference highlights the characteristics of people with T2D at high CV risk or with CV complications enrolled in the CAROLINA (
utcome Study of
gliptin versus Glimepiride in Early Type 2 Diabetes) study. This study is investigating the long-term CV safety of linagliptin compared to glimepiride and to evaluate their effects on CV outcomes in these high-risk patients.
"There is a well-established association between cardiovascular events and type 2 diabetes," said Professor Odd-Erik Johansen, senior clinical program leader, Boehringer Ingelheim. "In fact, cardiovascular events rank as the major cause of death in patients with diabetes, accounting for more than 65 percent of all diabetes fatalities.
It is, therefore, important to evaluate treatments within this context in order to inform clinical decision-making when selecting a therapy in type 2 diabetes."
About the Pooled Analysis
For the post-hoc analysis, researchers pooled results from 19 double-blind studies, including data from 9,459 patients treated with either linagliptin (5mg: 5,687, 10mg: 160) or a comparator group of placebo and other oral antihyperglycemic treatments (placebo: 2,675, glimepiride: 775, voglibose: 162). The cumulative patient exposure (the total length of time all patients had been exposed to treatment) was 4,421 patient-years in the linagliptin group and 3,255 patient-years in the comparator group. The primary endpoint of the pooled analysis was a composite of CV death, non-fatal stroke, non-fatal myocardial infarction (MI) and hospitalization for unstable angina pectoris (UAP). CV events were prospectively adjudicated by a blinded independent expert committee.
The post-hoc meta-analysis showed a lower incidence rate of the composite CV endpoint for the linagliptin group (13.4 per 1,000 patient years), versus the comparator group (18.9 per 1,000 patient years), and a hazard ratio of 0.78 (CI: 0.55, 1.12, p=NS).
CAROLINA is evaluating the long-term impact of treatment with linagliptin and glimepiride on CV death and disability, and is the only ongoing long-term CV outcome trial of a DPP-4 inhibitor versus a single active comparator (glimepiride). The baseline patient characteristics for the study patients (n=6,103), published in the ADA Scientific Sessions Abstract book, showed that the recruited patient population is reflective of the target population with early type 2 diabetes and an increased risk for CV events.
Results from the double-blind, active controlled, event-driven trial are expected in 2018.
The CAROLINA baseline patient characteristics include the following:
- 33.7 percent have previous CV complications
- 41 percent have diabetes for less than five years; 28 percent have diabetes for up to 5-10 years
- 72.5 percent have a baseline HbA 1c<7.5 percent
- 67.3 percent were on one glucose-lowering agent; 22.3 percent were on two agents
- 89.1 percent of patients on monotherapy receiving metformin
- 46 percent are obese (BMI≥30 kg/m 2)
- 84.2 percent are on an antihypertensive therapy; 60 percent are on a statin; 47.5 percent are on aspirin
Linagliptin, which is marketed as Tradjenta® (linagliptin) tablets in the U.S., is a once-daily 5mg 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). If you have had inflammation of the pancreas (pancreatitis) in the past, it is not known if you have a higher chance of getting pancreatitis while you take TRADJENTA. Linagliptin is a DPP-4 inhibitor that does not require dose adjustments, regardless of declining renal function or hepatic impairment. There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with TRADJENTA or any other antidiabetic drug.