Boehringer Ingelheim and Eli Lilly and Company have announced that the European Commission has approved an expanded therapeutic indication for the DPP-4 inhibitor Trajenta® (linagliptin) to include use in combination with insulin in adults with Type 2 Diabetes.
“We are delighted that approval has been granted for the use of linagliptin as an add-on to insulin in adults with Type 2 Diabetes,” said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim, “This expanded indication shows that linagliptin is an effective treatment for patients at various stages of Type 2 Diabetes.”
The approval means linagliptin is now indicated for use in combination with insulin with or without metformin, when this regimen alone, with diet and exercise, does not provide adequate glycaemic control.
The approval is based on data from a number of clinical studies, including efficacy data from a Phase III trial of at least 52 weeks duration demonstrating the efficacy and safety profile of linagliptin in combination with basal insulin (primary endpoint: efficacy after 24 weeks). The trial results showed that after 24 weeks, adding linagliptin to insulin produced better glucose control than insulin alone, without an additional risk of hypoglycaemia.
The US FDA approved linagliptin for use as add on to insulin in adults with Type 2 Diabetes in August 2012.
Linagliptin is an inhibitor of the enzyme DPP-4 (dipeptidyl peptidase-4) which is involved in the inactivation of the incretin hormones GLP-1 and GIP (glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide). Linagliptin glucose-dependently increases insulin secretion and lowers glucagon secretion thus resulting in an overall improvement in the glucose homoeostasis.
Linagliptin (5mg, once-daily) is marketed as Trajenta® across Europe and Canada, as Tradjenta® in the US, and Trazenta® in Japan, as well as in additional markets.(2)
Linagliptin is a prescription medicine that is used along with diet and exercise to lower blood glucose in adults with Type 2 Diabetes.(2,3) Linagliptin is not for people with Type 1 Diabetes nor for people with diabetic ketoacidosis (increased ketones in the blood or urine).(2,3)
About the clinical trial
Insulin add-on therapy trial
The efficacy of linagliptin as add-on to insulin therapy was evaluated in a 52-week randomised, double-blind, placebo-controlled trial with the primary endpoint measured after 24 weeks. In the trial, a total of 1,261 patients with Type 2 Diabetes inadequately controlled on insulin glargine, insulin detemir, or NPH insulin were randomised to receive either linagliptin 5 mg once daily or placebo. The trial included patients with a baseline HbA1c of ≥7% and ≤10%, including 709 patients with renal impairment, most of whom were categorised as having mild renal impairment (eGFR 60 to <90 ml/min). HbA1c is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months. Patients were kept on a stable dose on insulin prior to and during the trial for the first 24 weeks. A total of 16.1% of patients did not take oral antidiabetic drugs at baseline, 75.6% took metformin only, 7.3% took both metformin and pioglitazone, and 1.0% took pioglitazone only.(1)
At 24 weeks, linagliptin on a background of insulin therapy demonstrated a placebo-adjusted reduction in haemoglobin HbA1c of -0.65% from a baseline HbA1c of 8.3%. The differences in HbA1c seen between linagliptin and placebo were comparable for patients with or without renal impairment, and regardless of the severity of impairment. The overall frequency hypoglycaemia (linagliptin, 25.7%; placebo, 27.3%) was not higher with linagliptin than with placebo. Overall body weight did not differ significantly between treatment groups.(1)
- 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 72nd Scientific Sessions of the American Diabetes Association (ADA). June 8-12, 2012, Philadelphia, PA.
- Trajenta® (linagliptin) tablets. EMA Summary of Product Characteristics. Approval 25 September 2011. www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002110/WC500115745.pdf
- Tradjenta™ (linagliptin) tablets. Highlights of Prescribing Information. Initial U.S. Approval: 2011.