Two dose‐ranging studies with PF‐04937319, a systemic partial activator of glucokinase, as add‐on therapy to metformin in adults with type 2 diabetes. Issue 8 (11th May 2015)

• Record Type: Journal Article
• Authors: Amin, N. B.; Aggarwal, N.; Pall, D.; Paragh, G.; Denney, W. S.; Le, V.; Riggs, M.; Calle, R. A.
• Is Part Of: Diabetes, obesity & metabolism. Volume 17:Issue 8(2015:Aug.)
• Page Start: 751
• Page End: 759
• Publication Date: 2015-05-11
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12474
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12474-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dom12474-sec-0001" sec-type="section"> <title>Aim</title> <p id="dom12474-para-0001">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).</p> </sec> <sec id="dom12474-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12474-para-0002">Patients were randomized to once‐daily PF‐04937319 doses of 10, 50, 100 mg, or matching placebo (Study B1621002); or PF‐04937319 doses of 3, 20, 50, 100 mg, 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.</p> </sec> <sec id="dom12474-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12474-para-0003">In the 639 patients randomized, the minimally efficacious PF‐04937319 dose was identified as 50 mg once daily. At the highest PF‐04937319 dose tested (100 mg), on average, a clinically significant reduction in HbA1c [−4.94 or −5.11 mmol/mol (−0.45 or −0.47%), placebo‐adjusted], which was similar to that achieved with sitagliptin [−4.69 mmol/mol (−0.43%)] but lower than that achieved with titrated glimepiride [−9.07 mmol/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 +0.50 mmol/l). PF‐04937319 was well tolerated at doses up to 100 mg. Hypoglycaemia was reported in 2.5% of patients (on placebo), 5.1% of patients (on PF‐04937319 100 mg), 1.8% of patients (on sitagliptin) and 34.4% of patients (on titrated glimepiride).</p> </sec> <sec id="dom12474-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12474-para-0004">In patients on metformin monotherapy, the addition of a 100‐mg dose of PF‐04937319 improved glycaemic control and was well tolerated.</p> </sec> </abstract>