Linagliptin in Phase III Trial Confirm Favourable Efficacy and Safety

Professor Klaus Dugi, Head of Corporate Medical Affairs, at Boehringer Ingelheim stated that, “It is important that treatments for Type 2 diabetes not only help patients to achieve optimal blood glucose levels, but also ensure that glucose control is stable and long-term. Therapies to date have not been able to achieve constant long-term glucose control, and the traditional combinations have shown an increased risk of side-effects, such as hypoglycemia.”

“First data from the phase III clinical trial program so far suggest that linagliptin is likely to achieve these goals,” Professor Dugi reported. The trials have randomized more than 5,000 patients, with four pivotal phase 3 trials now completed. He noted that phase II data showed that linagliptin (5mg) reduced HbA1c by 0.73% and had a safety profile comparable to placebo, with no cases of hypoglycemia. The agent fits very tightly into the target enzyme, which results in its being the most potent DPP-4 inhibitor, with a long duration of action, he explained. Its primarily non-renal route of excretion may be an advantage in patients with renal impairment, he suggested, noting that up to half of people with diabetes have mild renal impairment.

Emphasising the need for better treatment options, Professor Ele Ferannini, Professor of Internal Medicine, University of Pisa School of Medicine, Italy, warned that Type 2 diabetes is now one of the most common non-communicable diseases, with rates increasing across the world. “Diabetes is a chronic, progressive condition which needs long-term management. Treatments must have a low side-effect profile and be convenient for patients to take, to achieve long-term adherence,” he said, noting that compliance with treatments for chronic diseases is a major problem.

“Diabetes and its complications pose a significant financial burden on individuals, healthcare systems and societies,” he said, adding that only 25% of health spending on diabetes in industrialized countries is on glucose lowering treatments, while the remainder is spent on managing the complications.

Professor Ferannini considered that there is a particular need to improve the management of “difficult to treat groups” with diabetes. These include the elderly, where there are particular concerns about the risk of falls due to hypoglycaemia; patients with renal impairment who currently have limited treatment options; patients with comorbidities requiring additional treatments that can reduce the efficacy of glucose lowering therapies; patients whose glucose levels are inadequately controlled; and those with cardiovascular disease, where there is a need to reduce the additional risk of cardiovascular complications.

Professor Anthony Barnett, Professor of Medicine, Heart of England NHS Foundation Trust, Birmingham UK, explained that effective glucose control is very important in reducing the risk of complications. He noted that a 1% reduction in HbA1c correlates with a 14% reduction in the risk of myocardial infarction, a 37% reduction in microvascular complications, and a 21% reduction in deaths due to diabetes. “There is a great need for effective glucose control strategies to achieve these reductions in practice,” he said.

At the same time, diabetes treatment needs to be well tolerated, he added, “Many traditional diabetes drugs, including sulphonylureas and insulin, can cause hypoglycemia, which can be devastating in certain circumstances.” He reported that a UK study revealed that 7% of diabetes patients on SU’s have a severe hypoglycemic episode each year, and a further 40% have symptomatic hypoglycemia.

Professor Barnett suggested that DPP-4 inhibitors have several benefits, including ease of use — with daily oral dosing, low risk of hypoglycemia, causing no increase in weight and being very well tolerated. 

A report at the Study of Diabetes annual meeting, EASD, Oct. 2, 2009.