Date: 2012-06-09
Type of information:
phase: 3
Announcement: results from two randomized phase 3 clinical trials and a post-hoc analysis for linagliptin at the American Diabetes Association's (ADA's) 72nd Scientific Sessions :
• 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. Abstract #999-P. Presented at the American Diabetes Association\'s (ADA\'s) 72nd Scientific Sessions®. June 8-12, Philadelphia, PA.
• Barnett A, Huisman H, Jones R, et al. Efficacy and Safety of Linagliptin in Elderly Patients (?70 Years) With Type 2 Diabetes. Abstract #1017-P. Presented at the American Diabetes Association\'s (ADA\'s) 72nd Scientific Sessions®. June 8-12, Philadelphia, PA.
• Gallwitz B, Rosenstock J, Emser A, 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. Abstract #1044-P. Presented at the American Diabetes Association\'s (ADA\'s) 72nd Scientific Sessions®. June 8-12, Philadelphia, PA.
Company: Boehringer Ingelheim (Germany) - Eli Lilly (USA)
Product: linagliptin (Tradjenta® in the US and Trajenta® in Europe)
Action
mechanism: Tradjenta® is a dipeptidyl peptidase-4 (DPP-4) inhibitor.
Disease: type 2 diabetes
Therapeutic area: Metabolic diseases
Country:
Trial
details: Abstract 999-P Study Design and Safety
This 52-week, multicenter, randomized, placebo-controlled phase 3 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 type 2 diabetes. The study included 1,261 patients who had inadequate glycemic control with a stable dose of basal insulin with or without metformin and/or pioglitazone (i.e., insulin glargine, insulin detemir or NPH insulin).Patients were randomized to receive either 5 mg of linagliptin or placebo once daily. The primary efficacy endpoint was the mean change in A1C from baseline to week 24, during which time the basal insulin and metformin and/or pioglitazone dose remained stable.
The overall frequency of adverse events (linagliptin, 71.8 percent versus placebo, 72.5 percent) and hypoglycemia (linagliptin, 25.7 percent versus placebo, 27.3 percent) were similar in both groups.(1) In addition, body weight did not significantly change from baseline (-0.17 kg +/- 0.11 versus +0.13 kg +/- 0.12; p=0.07) in the linagliptin and placebo groups, respectively.
Abstract 1017-P Study Design and Safety
This randomized, placebo-controlled, double-blind phase 3 study evaluated the efficacy and safety of linagliptin 5 mg daily in 241 elderly patients (74.9 years +/- 4.3 years) with type 2 diabetes, who had insufficient glycemic control despite treatment with metformin, sulfonylurea and/or insulin therapy. Patients were randomized to receive either 5 mg of linagliptin once daily, or placebo as an add-on to stable background therapy over 24 weeks.[2] Patients were taking either metformin (84.9 percent), sulfonylurea (57.6 percent) or insulin therapy (21.0 percent). Baseline A1C was 7.8 percent and 7.7 percent in the linagliptin and placebo groups, respectively.[2] Drug-related adverse events were experienced by 21.0 percent and 13.9 percent of linagliptin and placebo patients, respectively. Hypoglycemia occurred in 24.1 percent and 16.5 percent, respectively (p=0.1625).[2]
Abstract 1044-P Study Design and Safety
An exploratory analysis of a 104-week study assessed the proportions of adult patients with type 2 diabetes treated with linagliptin versus glimepiride both on a background of metformin who achieved a glycemic target of A1C <7 percent without weight gain (defined as <1kg increase in body weight versus baseline) and without hypoglycemia (defined event per protocol).
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 A1C thresholds). A total of 504 patients were evaluable (233 linagliptin; 271 glimepiride). Baseline A1C levels were similar in the two groups (linagliptin, 7.2 percent and glimepiride, 7.3 percent).[3] Six percent of linagliptin patients experienced hypoglycemia versus 22 percent on glimepiride and 22 percent experienced weight gain, versus 55 percent on glimepiride. Consequently, a significantly higher proportion in the linagliptin group than with the glimepiride group achieved the composite endpoint (54 percent versus 23 percent, respectively).
Latest
news: Boehringer Ingelheim and Eli Lilly have presented results from two randomized phase 3 clinical trials and a post-hoc analysis for linagliptin at the American Diabetes Association's (ADA's) 72nd Scientific Sessions®. The new studies provide additional data evaluating the efficacy and safety of linagliptin (alone or in combination with other diabetes therapies) in adults with type 2 diabetes.
• Interim results of the first phase 3 study presented here (abstract #999-P) showed that adding linagliptin to a background of basal insulin – alone or in combination with metformin and/or pioglitazone – demonstrated a placebo-adjusted reduction in hemoglobin A1c (HbA1c or A1C) of 0.65 percent from a baseline A1C of 8.3 percent[1] at 24 weeks versus adding placebo to these background therapies in adult patients 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.
• In a second phase 3 study (abstract #1017-P), linagliptin showed a 0.64 percent placebo-adjusted reduction in A1C (p<0.0001) at 24 weeks from baseline (A1C = 7.8 percent) in elderly patients (mean age 74.9 years) insufficiently controlled despite previous treatment with metformin and/or sulfonylurea and/or insulin therapy. Hypoglycemia occurred in 24.1 percent of patients on linagliptin versus 16.5 percent of patients on placebo.[2]
• The third abstract was a post-hoc analysis (abstract #1044-P) in which patients with uncontrolled A1C on a background of metformin were randomized to add-on linagliptin or glimepiride. The endpoint of the 104-week exploratory analysis was to assess the proportions achieving a glycemic target A1C <7 percent without weight gain (defined as <1 kg increase in body weight vs baseline) and without hypoglycemia. After 104 weeks of treatment, both linagliptin and glimepiride reduced mean A1C levels by 0.6 percent from baseline (baseline: 7.2 percent linagliptin, 7.3 percent glimepiride) and 76 percent of patients in both groups achieved target A1C <7 percent. Analyses were based on a per protocol population on treatment after 104 weeks without the use of rescue medication. Fewer patients taking linagliptin versus glimepiride experienced hypoglycemia (very low blood sugar levels) and weight gain during the trial period (6 percent versus 42 percent and 22 percent versus 55 percent, respectively). A significantly higher proportion in the linagliptin group than the glimepiride group achieved the composite endpoint (54 percent versus 23 percent, respectively).
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in the field of diabetes that centers on four pipeline compounds, including LY2605541 (See http://biopharmanalyses.fr/agreements/?pageid=204).
