Date: 2012-10-02
Type of information:
phase: 3
Announcement: presentation of data from three pooled analyses for linagliptin at the 48th European Association for the Study of Diabetes (EASD) Annual Meeting in Berlin.
Company: Boehringer Ingelheim (Germany) Eli Lilly (USA)
Product: Tradjenta® (linagliptin)
Action mechanism:
Disease: type 2 diabetes
Therapeutic area: Metabolic diseases
Country:
Trial
details: Poster #850 Study Design
This post-hoc analysis included seven randomized, double-blind, placebo-controlled phase III trials of linagliptin 5 mg once daily as monotherapy or add-on to various glucose-lowering therapies of at least 24 weeks\' duration. The trial included 1,331 patients aged 65 years, including 841 patients on linagliptin and 490 patients on placebo. Overall, 21 percent of patients had renal function decline, more than 80 percent had diabetes for at least five years, and more than 60 percent were receiving two or more glucose-lowering drugs.
Presentation #36 Study Design
Data from seven randomized, double-blind, 24- to 52-week, placebo-controlled trials of linagliptin monotherapy or as add-on to various glucose-lowering medicines were pooled for the analysis. This included patients from four clinical trials (n=2,472) who had early diabetic nephropathy and were on stable ACE/ARB therapy and elderly patients from all seven trials (n=377) who had diabetic nephropathy and met the UACR inclusion criteria (30 to 3,000 mg/g creatinine). The endpoint in both data sets was the percentage change in geometric mean UACR after 24 weeks of treatment. In all trials, blood pressure and renal function were not affected to a clinically-meaningful extent by either treatment.
Presentation #6 Study Design
In the 52-week insulin study, a total of 1,261 patients inadequately controlled on basal insulin (glargine, insulin detemir, or NPH insulin) were randomized to receive linagliptin 5 mg once daily or placebo. Background basal insulin had to be kept stable for the first 24 weeks but could then be adjusted as needed, to mirror real-world use with basal insulin.
Poster #848 Study Design
Data from two phase III studies evaluating linagliptin vs. placebo as add-on therapy to basal insulin and as T2D management in elderly patients (age >70 years) were pooled for a pre-specified analysis exploring its safety and efficacy. A total of 247 patients inadequately controlled on insulin glargine, insulin detemir, or NPH insulin received either linagliptin 5 mg once daily (n=126) or placebo (n=121). Mean insulin doses were 35.0 IU and 36.6 IU, respectively. The primary efficacy endpoint was change from baseline to week 24 in A1C. Safety and tolerability based on AEs also were assessed.
Latest
news: Boehringer Ingelheim Pharmaceuticals and Eli Lilly and Company have announced data from three pooled analyses for linagliptin at the 48th European Association for the Study of Diabetes (EASD) Annual Meeting in Berlin. The new analyses show linagliptin, alone or in combination with other diabetes therapies, lowered hemoglobin A1c (HbA1c or A1C) in elderly patients with type 2 diabetes, as well as in adults with type 2 diabetes with diabetic nephropathy (renal disease). Data from a fourth study found adding linagliptin to a stable dose of basal insulin improved blood glucose control over 52 weeks without an additional risk of hypoglycemia or weight gain compared to placebo.
An analysis of data pooled from seven phase III trials among 1,331 patients (poster #850) showed linagliptin, used alone or as add-on to various glucose-lowering therapies, had a placebo-adjusted reduction in A1C of 0.62 percent from a baseline A1C of 8.0 percent at 24 weeks in elderly patients (>65 years) with type 2 diabetes. A1C is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months. These patients also experienced a placebo-adjusted reduction in fasting plasma glucose (FPG) of 14.8 mg/dL.
Adverse events (AEs) were experienced by 71.3% and 73.3% of patients who received linagliptin and placebo, respectively, and drug-related AEs were reported in 18.1% of patients treated with linagliptin compared with 19.8% of patients treated with placebo. The incidence of hypoglycemia was 21.4% in patients who received linagliptin compared with 25.7% in patients who received placebo. Severe hypoglycemic events requiring assistance were reported in both groups (1.0% and 1.8%, respectively). Overall AE reporting for GI disorders was comparable between both groups (14.1% and 15.5%, respectively).
A second post-hoc analysis of seven randomized trials with treatment durations of 24 to 52 weeks (Presentation #36) assessed the clinical effect of linagliptin on albuminuria in adult and elderly (>65 years) patients with type 2 diabetes who had diabetic nephropathy (n=2,472). The primary endpoint of the analysis was changes to the urinary albumin-to-creatinine ratio (UACR) – a measure of glomerular integrity in patients with type 2 diabetes and diabetic nephropathy – after week 24. Overall, patients treated with linagliptin showed a significant reduction in UACR. This included a 29 percent placebo-adjusted reduction in UACR among patients with type 2 diabetes receiving linagliptin with or without oral glucose-lowering therapies and stable treatment with one of two types of blood pressure medicines that are the standard treatment for diabetic renal disease (angiotensin-converting enzyme inhibitors [ACEs] and angiotensin receptor blockers [ARBs]), and also a 30 percent reduction in UACR among elderly patients with diabetic nephropathy.2
In a third abstract (presentation #6), patients with type 2 diabetes treated with linagliptin in combination with a stable dose of basal insulin showed a placebo-adjusted reduction in A1C of 0.53 percent from baseline after 52 weeks (n=1,261). This was accompanied by a mean change in basal insulin dose of +2.6 +/- 0.8 IU/day for linagliptin plus basal insulin vs. +4.2 +/- 0.8 IU/day for placebo plus basal insulin. The incidence of hypoglycemia was similar between the groups (linagliptin, 31.4%; placebo, 32.9%), as was the number of severe hypoglycemic events over one year (linagliptin, 1.7%; placebo, 1.1%). In addition, the average changes in body weight were comparable between the treatment groups (linagliptin, -0.30 +/- 3.7kg; placebo, -0.04 +/- 3.1kg).
In a fourth abstract (poster #848), linagliptin as add-on to basal insulin therapy vs. placebo also was studied in elderly patients (>70 years) in a separate pre-specified pooled analysis of two Phase III studies over 24 weeks (poster #848). Linagliptin achieved improvements in glycemic control of -0.77% (placebo-adjusted change in A1C from baseline [P<0.0001]), with a rate of hypoglycemia of 28.6% in linagliptin-treated patients and 37.2% in placebo-treated patients. In this population, the overall incidence of AEs for linagliptin in combination with basal insulin was not higher than placebo (75.4% and 81.0%, respectively).3
