Aim: To assess the efficacy and safety of a range of doses of a systemic, partial, glucokinase activator, PF-04937319, as add-on therapy to metformin, in patients with type 2 diabetes mellitus (T2DM). Methods: Patients were randomized to once-daily PF-04937319 doses of 10, 50, 100mg, or matching placebo (Study B1621002); or PF-04937319 doses of 3, 20, 50, 100mg, or matching placebo (Study B1621007). Titrated glimepiride (Study B1621002) or sitagliptin (Study B1621007) were included in a double-dummy manner. The primary measure was change from baseline in glycated haemoglobin (HbA1c) at week 12. Key secondary measures included other glycaemic variables and safety and tolerability. Results: In the 639 patients randomized, the minimally efficacious PF-04937319 dose was identified as 50mg once daily. At the highest PF-04937319 dose tested (100mg), on average, a clinically significant reduction in HbA1c [-4.94 or -5.11mmol/mol (-0.45 or -0.47%), placebo-adjusted], which was similar to that achieved with sitagliptin [-4.69mmol/mol (-0.43%)] but lower than that achieved with titrated glimepiride [-9.07mmol/mol (-0.83%)], was observed. At this dose, the effect on fasting plasma glucose was not consistent between the two studies (Study B1621002 vs Study B1621007: placebo-adjusted mean change of -0.83 vs +0.50mmol/l). PF-04937319 was well tolerated at doses up to 100mg. Hypoglycaemia was reported in 2.5% of patients (on placebo), 5.1% of patients (on PF-04937319 100mg), 1.8% of patients (on sitagliptin) and 34.4% of patients (on titrated glimepiride). Conclusions: In patients on metformin monotherapy, the addition of a 100-mg dose of PF-04937319 improved glycaemic control and was well tolerated.
- Glycaemic control
- Type 2 diabetes
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism