Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) today announced Phase III study results for linagliptin (proposed trade name Trajenta® in Europe), demonstrating improved glycaemic control in adults with type 2 diabetes (T2D) whose blood glucose is not adequately maintained. In one long-term study over two years evaluating linagliptin or glimepiride when added to metformin, linagliptin was as effective at lowering blood glucose as glimepiride, as measured by haemoglobin A1C (HbA1c) but with relative weight loss (-1.4 kg vs. +1.5 kg; adjusted mean difference, -2.9 kg; p<0.0001), reduced incidence of hypoglycaemia (7.5 percent vs. 36.1 percent; p<0.0001) and fewer cardiovascular (CV) events (1.5 percent vs. 3.4 percent; Relative Risk 0.46 [0.23-0.91]>1 Results will be presented at the 71st Annual American Diabetes Association (ADA) Scientific Sessions in San Diego, 24 - 28 June.
"The combination of linagliptin plus metformin provides meaningful glucose control comparable to that of a combination of a sulphonylurea plus metformin. The added benefit is that, unlike a sulphonylurea, linagliptin is not associated with weight gain and does not per se increase the occurrence of hypoglycaemia," said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "In addition, compared to the sulphonylurea glimepiride, linagliptin was associated with a 54 percent relative risk reduction for cardiovascular events in this study. This highlights the promising cardiovascular safety data seen with linagliptin to date which we are currently further exploring in the CAROLINA study."
Another study of 24-weeks evaluating linagliptin demonstrated mean placebo-corrected HbA1c reductions of up to 1.7 percent from baseline when linagliptin 2.5 mg twice daily (bid) was used in combination with metformin 1,000 mg bid in T2D patients with insufficient glycaemic control. The combination of linagliptin plus metformin was well tolerated and improved glycaemic control more than either medication when used alone. In the trial, there was no weight gain with the linagliptin plus metformin combination, and a very low risk of hypoglycaemia (five cases, or 1.8 percent of patients). In an open label arm including patients with poor glycaemic control (HbA1c at baseline >11 percent) linagliptin 2.5 mg twice daily (bid) in combination with metformin 1,000 mg bid achieved a reduction from baseline of HbA1c of 3.7 percent.
Linagliptin was also evaluated in T2D patients with different degrees of renal function. A large pooled analysis of three randomised, placebo-controlled Phase III trials. In an additional study evaluating T2D patients with severe renal impairment (RI) whose blood glucose was insufficiently controlled, linagliptin provided a clinically meaningful placebo-corrected HbA1c reduction of -0.6 percent (p<0.0001) after 12 weeks of treatment. Renal function remained stable over time and CV deaths in this high-risk population were low with one patient per arm.
"Renal impairment is frequently associated with type 2 diabetes, and is a major factor in limiting the choice of glucose-lowering agents," said Mark Cooper, MD, deputy director and chief scientific officer, Baker IDI Heart and Diabetes Institute, Australia. "In this trial, linagliptin was effective at lowering A1C, even in patients with poor glycaemic control and renal impairment."
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