The US Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for Tradjenta (linagliptin) tablets of Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company for use as add-on therapy to insulin.

Tradjenta is a prescription medication used along with diet and exercise to lower blood sugar in adults with type 2 diabetes, and can be used as monotherapy or in combination with other commonly prescribed medications for type 2 diabetes, such as metformin, sulfonylurea, pioglitazone or insulin. Tradjenta should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine).

The FDA's decision is based on data from a 52-week, phase III trial demonstrating the efficacy of Tradjenta in combination with insulin (with or without metformin and/or pioglitazone). The trial results showed adding Tradjenta to insulin produced better glucose control than insulin alone, with similar incidence of hypoglycemia (low blood sugar) in both treatment groups. Tradjenta belongs to a class of prescription medications called dipeptidyl peptidase-4 (DPP-4) inhibitors and is the first member of its class to be approved at one dosage strength (5 mg, once-daily).

Additionally, the FDA-approved label includes a clinical study in people with severe chronic renal impairment. Data from a 52-week, double-blind, randomized, placebo-controlled trial showed that use of Tradjenta 5 mg plus other glucose-lowering therapies in this patient population provided a statistically significant improvement in glycated haemoglobin (HbA1c or A1C) compared to placebo (placebo-adjusted reduction of 0.7 per cent).

"Many people with type 2 diabetes taking insulin also require additional medication. With today's FDA decision, Tradjenta can be an effective add-on therapy with a demonstrated safety profile to help adult patients on insulin to improve their blood sugar control," said John Smith, MD, PhD, senior vice president for clinical development and medical affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Tradjenta is the only once-daily, one-dose drug in its class without the need for dose adjustment regardless of declining renal function or hepatic impairment."

Tradjenta lowers blood sugar in a glucose-dependent manner by increasing incretin levels, which increase insulin levels after meals and throughout the day. Among many considerations when treating patients with type 2 diabetes, approximately 40 per cent of individuals have some degree of renal impairment. With Tradjenta, no dose adjustment is required regardless of declining renal function or hepatic impairment.

The efficacy of Tradjenta as an add-on to basal insulin therapy was evaluated in a 52-week randomized, double-blind, placebo-controlled trial with the primary endpoint measured after 24 weeks. In this trial, a total of 1,261 patients with type 2 diabetes inadequately controlled on insulin glargine, insulin detemir, or NPH insulin were randomized to receive either Tradjenta 5 mg once daily or placebo. The trial enrolled patients with a baseline A1C of greater than or equal to seven per cent and less than or equal to 10 per cent, and included 709 patients with renal impairment, most of whom were categorized as having mild renal impairment (estimated glomerular filtration rate [eGFR] 60 to < 90 ml/min). A1C is measured in patients with diabetes to provide an index of blood glucose control for the previous two to three months. Patients were kept on a stable dose of insulin prior to and during the trial for the first 24 weeks. Additional background therapy combinations included basal insulin plus metformin (75.5 per cent), basal insulin plus metformin and pioglitazone (7.4 per cent), and basal insulin plus pioglitazone (one per cent).

The primary endpoint of this trial was change in A1C after 24 weeks of treatment. At 24 weeks, Tradjenta plus basal insulin demonstrated a placebo-adjusted reduction in haemoglobin A1C of 0.65 per cent from a baseline A1C of 8.3 per cent. The mean change in basal insulin dose after 24 weeks was +0.6 IU/day for Tradjenta versus +1.3 IU/day for placebo.1 The differences in A1C seen between Tradjenta and placebo were comparable for patients with or without renal impairment, and regardless of the severity of impairment. Overall the mean change in body weight from baseline to week 24 was similar in both treatment groups. The rate of hypoglycaemia also was similar in both groups (21.4 per cent, Tradjenta and 22.9 per cent, placebo) in the first 24 weeks of the study. The use of Tradjenta in combination with insulin in patients with severe renal impairment was associated with a higher rate of hypoglycaemia.

In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in the field of diabetes that centres on four pipeline compounds representing several of the largest treatment classes. This alliance leverages the companies' strengths as two of the world's leading pharmaceutical companies, combining Boehringer Ingelheim's solid track record of research-driven innovation and Lilly's innovative research, experience, and pioneering history in diabetes. By joining forces, the companies demonstrate commitment in the care of patients with diabetes and stand together to focus on patient needs.