Two Phase III studies have shown that Boehringer Ingelheim’s (BI) once-daily oral type 2 diabetes candidate linagliptin effectively reduces blood sugar levels either when given as monotherapy in patients unable to receive metformin, or when administered in combination with sylfonylurea in inadequately controlled patients with type 2 diabetes. New pharmacokinetic data also suggests that poor renal function has little effect on elimination of the dipeptidyl peptidase 4 inhibitor. BI suggests this finding means that type 2 diabetes patients with renal impairment may not need to adjust their linagliptin dose. The firm aims to make regulatory filings for linagliptin in major global markets during 2010.
Data from the two Phase III linagliptin trials were presented at the "Annual Meeting of the European Association for the Study of Diabetes". Earlier this week positive pivotal trial data was reported for two potentially competing type 2 diabetes drugs, dapagliflozin (Bristol-Myers Squibb and AstraZeneca) and lixisenatide (sanofi-aventis).
The linagliptin data emerged from two pivotal studies. The placebo-controlled monotherapy trial involved patients for whom metformin therapy was inappropriate. The trial found statistically significant treatment-related differences in HbA1c levels between placebo-treated patients and those receiving linagliptin by week six. The placebo-adjusted mean difference was -0.57% at week 18. Among those patients who started the trial with HbA1c levels of over 7%, an HbA1c level of less than 7% was achieved by 23% of linagliptin-treated patients, compared with just 11.8% of placebo patients. Linagliptin therapy also resulted in significant reductions in fasting glucose, BI points out.
The Phase III trial evaluating linagliptin as an add-on to sylfonylurea also found that the investigational drug further pushed HbA1c levels down from baseline, by a mean of -0.47%.
In addition to linagliptin, Boehringer Ingelheim is developing a sodium-dependent glucose co-transporter-2 (SGLT-2) inhibitor, BI-10773, as a new type of antidiabetic compound that blocks tubular reabsorption of glucose in the kidney. Phase II trials for BI-10773 have been completed, the firm points out. Its type 2 diabetes pipeline also includes an early clinical-stage 11beta-HSD1 inhibitor, which is thought to act by lowering intracellular cortisol concentrations and improving insulin sensitivity, blood lipid levels, and vascular function.