Boehringer Ingelheim (BI) and Eli Lilly and Company have announced new data(1) from a Phase IV study evaluating linagliptin (5 mg) as monotherapy and in combination with metformin (1500 or 2000 mg) in treatment-naive adults with newly diagnosed (<12 months) uncontrolled Type 2 Diabetes (T2D). The result showed that linagliptin as monotherapy or in initial combination with metformin achieved clinically significant improvements in glucose control in patients with newly diagnosed T2D and marked hyperglycaemia. Results also showed both treatments provided statistically significant reductions in blood glucose levels, with the combination therapy having greater glucose reduction compared to monotherapy. The results were presented during the 2013 World Diabetes Congress, which is being held 2-6 December in Melbourne, Australia.
The study randomised 316 adults with a mean average plasma glucose concentration (HbA1c) of 9.8 percent to receive linagliptin 5 mg once-daily (n = 157) and the initial combination of linagliptin 5 mg once-daily plus metformin twice-daily (uptitrated to a maximal dose of 2000 mg/d; n = 159) for 24 weeks. The results showed:
- Linagliptin monotherapy and linagliptin + metformin initial combination therapy demonstrated statistically significant reductions in HbA1c of 2.0 percent and 2.8 percent, respectively.
- HbA1c reduction with the initial combination of linagliptin + metformin was statistically superior to linagliptin alone.
- A proportion of patients achieved a target HbA1c of <7 percent at week 24 with linagliptin + metformin and linagliptin monotherapy (61 percent and 39 percent, respectively)
- Both treatments were well tolerated overall with few drug-related or serious adverse events
- Hypoglycaemia occurred in 3.2 percent and 1.9 percent with linagliptin monotherapy and linagliptin + metformin initial combination therapy, respectively
- Body weight was stable with linagliptin and decreased in the combination arm (–1.3 kg between group difference)
"Improving glycaemic control in the early stages of Type 2 Diabetes is important, especially in adults with high glucose levels upon initial diagnosis," said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "The significant drop in HbA1c seen with both linagliptin monotherapy and in initial combination with metformin highlights the importance of these treatment choices for people with T2D."
The U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and several other regulatory authorities worldwide have approved linagliptin for the treatment of adults with T2D as monotherapy or in combination with metformin, metformin + sulphonylurea, and as add-on therapy to insulin. With linagliptin, except as fixed dose combination with metformin, no dose adjustment is required regardless of renal or hepatic function and hence, it can be used at one single dose in a broad range of patients.(2,3)
About the study In this international double-blind clinical trial, 316 treatment naïve subjects with recently diagnosed (<12 months) and uncontrolled T2D (baseline HbA1c 8.5 to 12.0 percent) were randomised to receive linagliptin 5 mg once daily (n=157) or the initial combination of linagliptin 5 mg once-daily plus metformin twice-daily (initial dose of 1000 mg/d uptitrated in the first six weeks; maximal dose 2000 mg/d; n=159) for 24 weeks. The primary endpoint was the difference in change from baseline HbA1c between groups in the per-protocol cohort of subjects completing the trial exclusively on study drug (linagliptin, n=113; linagliptin + metformin, n=132). The study did not include a placebo-controlled arm.
About Linagliptin
Linagliptin (5 mg) is marketed in Europe as Trajenta® (linagliptin) and in the U.S. as Tradjenta® (linagliptin), as a once-daily tablet that is used along with diet and exercise to improve glycaemic control in adults with T2D. Linagliptin should not be used in patients with Type 1 Diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine).(2,3)
About Linagliptin/Metformin HCl
Linagliptin/metformin HCl is marketed as Jentadueto® in the US and across Europe. It is also marketed in further markets such as Canada, Mexico and South Korea under different brand names, Trajentamet®, Trajenta Duo® and Trayenta Duo®. It is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with Type 2 Diabetes mellitus when treatment with both linagliptin and metformin is appropriate.
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). The use of linagliptin/metformin HCl in combination with insulin has not been adequately studied yet.
About Diabetes
An estimated 382 million people worldwide have Type 1 and Type 2 Diabetes.(4) Type 2 Diabetes is the most common type, accounting for an estimated 90 percent of all diabetes cases.5 Diabetes is a chronic disease 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 three compounds representing several of the largest diabetes 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.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavours.
In 2012, Boehringer Ingelheim achieved net sales of about €14.7 billion. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organisations. Headquartered in Indianapolis, IN, Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs.
1. S.A.Ross et al. A randomised controlled trial of linagliptin monotherapy vs. initial combination with metformin in newly diagnosed type 2 diabetes patients: Poster No: P-1104. Presented at the World Diabetes Congress, December 2-6, Melbourne
2. Trajenta® (linagliptin) tablets. EMA Summary of Product Characteristics. Approval 25 September 2011.
3. Tradjenta® (linagliptin) tablets. Highlights of Prescribing Information. Initial U.S. Approval: 2011.
4. International Diabetes Federation, IDF Diabetes Atlas 6th Edition, Brussels, 2013
5. World Health Organization. Fact Sheet No. 312 What is Diabetes? 2009 [cited 2013 January 2013]; Available from: http://www.who.int/mediacentre/factsheets/fs312/en/index.html
6. International Diabetes Federation. What is Diabetes? IDF Diabetes Atlas 6th Edition, Brussels, 2013