Jentadueto™ tablets recommended for approval in the treatment of adults with Type 2 Diabetes in Europe

Boehringer Ingelheim and Eli Lilly and Company today announced that they have received a positive opinion from the European Medicines Agency’s (EMA) medicinal committee recommending approval of Jentadueto™, which combines the DPP-4 inhibitor, linagliptin (the active ingredient in Trajenta® tablets) and metformin in a single tablet.¹ If approved by the European Commission, linagliptin/metformin hydrochloride (HCl) will provide a new, single-tablet treatment option, taken twice-daily, for adults with Type 2 Diabetes who need to improve control of their blood glucose.¹ In clinical studies, linagliptin/metformin HCl demonstrated benefit to patients by offering another dosing option with effective glycaemic control and a favourable side effect profile.

The Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of linagliptin/metformin hydrochloride (HCl) for use alongside diet and exercise to improve glycaemic control in adults with Type 2 Diabetes who are inadequately controlled on their maximal tolerated dose of metformin alone or those already being treated with the combination of linagliptin and metformin. In clinical trials, statistically significant, placebo-corrected mean reductions in haemoglobin A1c (HbA1c or A1C) levels of -1.7 percent were observed in patients with inadequate glycaemic control when the maximum dose of 2.5 mg linagliptin/1,000 mg metformin HCI was administered twice daily. 1 HbA1c is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months. In clinical studies, linagliptin/metformin HCl did not cause any significant change in body weight, and can be used alone or in combination with a sulphonylurea, a commonly prescribed medication for Type 2 Diabetes.

“The CHMP positive opinion for Jentadueto™ marks another important regulatory milestone for the Boehringer Ingelheim and Eli Lilly and Company worldwide diabetes alliance,” said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “Across Europe many people with Type 2 Diabetes require more than one treatment to adequately manage their diabetes. As a single-tablet treatment, we believe that Jentadueto™ will help patients with Type 2 Diabetes achieve and maintain glycaemic control and improve overall wellbeing.”

Linagliptin/Metformin HCl Clinical Trials

In a 24-week, randomised, double-blind, placebo controlled study evaluating 791 patients with Type 2 Diabetes and inadequate glycaemic control with diet and exercise, 2.5 mg linagliptin/1,000 mg metformin HCl twice daily demonstrated the following:¹

• Statistically significant, placebo-corrected mean HbA1c reductions of -1.7 percent
• Statistically significant reductions in fasting plasma glucose (FPG) of -60 mg/dL. FPG is used to determine glucose levels in a fasting state (usually upon waking in the morning)

The recommendation for approval of linagliptin/metformin HCl tablets was 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 with Type 2 Diabetes.^1,2

In clinical studies, adverse reactions were uncommon. Gastrointestinal disorders occurred most frequently during initiation therapy with linagliptin/metformin HCl or metformin HCl and tended to resolve spontaneously. A comparable rate of diarrhoea was reported with linagliptin/metformin HCl treatment versus metformin plus placebo (0.9 percent and 1.2 per cent respectively). Due to the impact of background therapy, 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, metformin and sulphonylurea (22.9 percent versus 14.8 percent, respectively).¹

Linagliptin (5 mg, 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.

About Linagliptin/Metformin HCl

Linagliptin/metformin HCl is not intended to be used in patients with Type 1 Diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine).^1,2

The use of linagliptin/metformin HCl in combination with insulin has not been adequately studied.^1,2

Subject to approval, linagliptin/metformin HCl is expected to be available in the following twice-daily doses in Europe: 2.5 mg linagliptin/850 mg metformin tablets and 2.5 mg linagliptin/1,000 mg metformin tablets.¹

About Linagliptin

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.¹

Linagliptin (5 mg, 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.^3,4

Linagliptin is a prescription medicine that is used along with diet and exercise to lower blood glucose in adults with Type 2 Diabetes.^3,4 Linagliptin is not for people with Type 1 Diabetes or for people with diabetic ketoacidosis (increased ketones in the blood or urine).^3,4 It is not known if linagliptin is safe and effective when used with insulin.⁴

About Diabetes

An estimated 366 million people worldwide have diabetes.⁵ Type 2 Diabetes is the most common type, accounting for an estimated 90 percent of all diabetes cases.⁵ Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.⁶

Boehringer Ingelheim and Eli Lilly and Company

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. Find out more about the alliance at www.boehringer-ingelheim.com or www.lilly.com.

References

1. Boehringer Ingelheim. Data on File.
2. Jentadueto™ (linagliptin/metformin HCI) tablets. Highlights of Prescribing Information. Initial US Approval: 2012
3. 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
4. Tradjenta™ (linagliptin) tablets. Highlights of Prescribing Information. Initial U.S. Approval: 2011.
5. International Diabetes Federation. Diabetes Atlas 5th edn. www.idf.org, 2010.
6. World Health Organization: Fact Sheet No. 312 What is Diabetes?, 2010.