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25 Sep 2013

Data From Post-Hoc Analyses Presented at EASD Examine Safety Profile of Linagliptin in Adults with Type 2 Diabetes

Boehringer Ingelheim and Eli Lilly and Company have 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 49th Annual Meeting of the European Association for the Study of Diabetes (EASD).

Linagliptin, which is marketed as TRADJENTA (linagliptin) tablets in the US, 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 7400 adults with T2D (4810 received linagliptin, 2590 received placebo) included the following(1):

     •  The hypoglycemic incidence rate for linagliptin compared with placebo was 11.5% versus 14%, respectively
     •  Overall incidence of adverse events (AE) or serious adverse events (SAE) with linagliptin was similar to placebo (AE 56.5% versus 61.2%, and SAE 4.8% versus 6.3%, 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(2) evaluated pooled data from seven randomized, placebo-controlled phase III clinical trials including 1293 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 versus -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 5.55 and 4.35 of linagliptin and placebo patients, respectively
     •  Incidence of investigator-defined hypoglycemia was lower in patients who received linagliptin compared with placebo (21.3% versus 24.7%), with most events occurring in trials that included a sulfonylurea or basal insulin as background therapy
     •  Acute renal failure occurred in 0.5% and 0.2% 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."

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.(3,4)


1. Lehrke M et al. Safety and tolerability of linagliptin in 7,400 patients  with Type 2 Diabetes: A pooled comprehensive analysis of prospective safety reporting in placebo-controlled studies. Poster No: 986. Presented
at the European Association for the Study of Diabetes (EASD), September 3-27, Barcelona.

2. Patel S et al. Renal safety of linagliptin in elderly patients with Type 2 Diabetes: analysis of pooled patient data from seven Phase III clinical trials. Poster No: 926. Presented at the European Association for the Study of Diabetes (EASD), September 23-27, Barcelona.

3. Tradjenta® (linagliptin) tablets. Highlights of Prescribing Information. Initial US Approval: 2011.

4. EMA. Trajenta® (linagliptin) tablets. EMA Summary of Product Characteristics. 2011.


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