FDA OKs Jentadueto Tablets for Treatment of Adults with Type 2 Diabetes

(Health & Beauty Close-Up)

Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company have announced that the U.S. Food and Drug Administration (FDA) has approved Jentadueto (linagliptin/metformin hydrochloride) tablets, a new tablet combining the dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, and metformin.

In a release, the companies noted: Linagliptin/metformin hydrochloride (HCl) provides a new, single- tablet treatment option, taken twice-daily, for adults with Type 2 Diabetes who need to improve control of their blood glucose.

Linagliptin (5 mg, once-daily) is marketed in the U.S. as Tradjenta (linagliptin) tablets, as Trajenta across Europe and Canada, and Trazenta in Japan, as well as in further markets. Linagliptin/metformin HCl is a prescription medication used along with diet and exercise to improve glycaemic control in adults with Type 2 Diabetes when treatment with both linagliptin and metformin is appropriate. At the maximum dose, linagliptin/metformin HCl demonstrated placebo-corrected reductions in haemoglobin A1c (HbA1c or A1C) levels of up to 1.7 percent (+0.1 percent for placebo and - 1.6 percent for linagliptin/metformin HCl). A1C is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months. Linagliptin/metformin HCl did not cause any meaningful change in body weight. Linagliptin/ metformin HCl can be used alone or in combination with a sulphonylurea, a commonly prescribed medication for Type 2 Diabetes. Linagliptin/metformin HCl are not for the treatment of Type 1 Diabetes or diabetic ketoacidosis (increased ketones in the blood or urine). It has not been studied in combination with insulin. The linagliptin/metformin HCl label contains a boxed warning for the risk of lactic acidosis, a serious metabolic complication that can occur due to metformin accumulation during treatment with linagliptin/metformin HCl.

"Most people with Type 2 Diabetes require more than one medication to help lower their blood sugar, due to the complex nature of Type 2 Diabetes," said Dr. Lance Sloan, Texas Institute for Kidney and Endocrine Disorders. "The approval of Jentadueto is exciting because it combines two diabetes medications in a single tablet, making it a good option for people who need an additional medication, and for whom both linagliptin and metformin is appropriate."

Linagliptin/Metformin HCl Clinical Trials

In a 24-week, randomised, double-blind, placebo-controlled factorial study evaluating 791 adults with Type 2 Diabetes and inadequate glycaemic control with diet and exercise, linagliptin plus metformin demonstrated the following:

Placebo

5 mg linagliptin once-daily

500 mgmetformin twice-daily

2.5 mg linagliptin/ 500 mg metformin twice-daily

1,000 mg metformin twice-daily

2.5 mg linagliptin/ 1,000 mg metformin twice-daily A1C ( percent) Change from baseline (adjusted mean) +0.1 -0.5 -0.6 -1.2 -1.1 -1.6 Difference from placebo (adjusted mean) -- -0.6 -0.8 -1.3 -1.2 -1.7 *FPG (mg/dL) Change from baseline (adjusted mean) +10 -9 -16 -33 - 32 -49 Difference from placebo (adjusted mean) -- -19 -26 -43 -42 - 60

Glycaemic parameters at final visit (24-week study) for linagliptin and metformin, alone and in combination in randomised adults with Type 2 Diabetes Mellitus inadequately controlled on diet and exercise (full analysis population using last observation on study)

*Fasting plasma glucose (FPG) is used to determine glucose levels in a fasting state (usually upon waking in the morning).

Linagliptin/metformin HCl tablets were approved based on clinical trials that evaluated linagliptin and metformin as separate tablets. Bioequivalence of linagliptin/metformin HCl was demonstrated with co- administered linagliptin and metformin tablets in healthy subjects.

Adverse reactions reported in greater than or equal to five percent of patients treated with linagliptin/metformin HCl and more commonly than in patients treated with placebo included nasopharyngitis (the common cold) and diarrhoea. Hypoglycaemia was more commonly reported in patients treated with the combination of linagliptin/metformin HCl and sulphonylurea compared with those treated with the combination of placebo, sulphonylurea and metformin (22.9 percent versus 14.8 percent, respectively). Pancreatitis was reported more often in patients randomised to linagliptin (1 per 538 person years versus zero in 433 person years for comparator).

"We are proud to bring this important, new treatment option combining linagliptin and metformin hydrochloride as a single- tablet, taken twice-daily, to the millions of people currently living with Type 2 Diabetes," said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim.

"We are hopeful that Jentadueto, the newest member of the growing family of products from the Boehringer Ingelheim and Lilly diabetes alliance, will help people living with blood glucose levels that are not adequately controlled."

The FDA approval of linagliptin/metformin HCl marks the second U.S. approval since the formation of the Boehringer Ingelheim and Eli Lilly and Company worldwide diabetes alliance in January 2011. The alliance leverages the collective scientific expertise and business capabilities of two leading research-driven pharmaceutical companies to address patient needs arising from the growing global diabetes epidemic. ((Comments on this story may be sent to health@closeupmedia.com))