Premium
Efficacy and safety of the dipeptidyl peptidase‐4 inhibitor PF‐734200 added to metformin in Type 2 diabetes
Author(s) -
Rosenstock J.,
Lewin A. J.,
Norwood P.,
Somayaji V.,
Nguyen T. T.,
Teeter J. G.,
Johnson S. L.,
Dai H.,
Terra S. G.
Publication year - 2011
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2010.03181.x
Subject(s) - medicine , metformin , dipeptidyl peptidase 4 inhibitor , type 2 diabetes , placebo , thiazolidinedione , diabetes mellitus , endocrinology , body mass index , gastroenterology , type 2 diabetes mellitus , confidence interval , insulin , alternative medicine , pathology
Diabet. Med. 28, 464–469 (2011) Abstract Aims PF‐734200 is a potent and selective oral dipeptidyl peptidase‐4 (DPP‐4) inhibitor. This study assessed the efficacy and safety of PF‐734200 at dose rates of 20 and 30 mg/day in subjects with Type 2 diabetes mellitus inadequately controlled on metformin monotherapy. Methods This was a placebo‐controlled, double‐blind, randomized, multicentre, 12 week study. Subjects with Type 2 diabetes mellitus were eligible if screening glycosylated haemoglobin (HbA 1c ) was 7–11% (53.0–96.7 mmol/mol) and they had been receiving metformin monotherapy for ≥2 months. Subjects receiving metformin and an insulin secretagogue or metformin and thiazolidinedione needed to have a screening HbA 1c of 6.5–9.5% (47.5–80.3 mmol/mol), measured prior to discontinuing the insulin secretagogue or thiazolidinedione. The primary end‐point of the study was a change from baseline to week 12 in HbA 1c levels. Results Baseline characteristics for 289 subjects randomized to PF‐734200 or placebo groups were similar (mean age 56.5 years, mean body mass index 32.2 kg/m 2 and mean HbA 1c 8.2%, 66.1 mmol/mol). In the predefined per protocol data set, least‐squares mean HbA 1c at week 12 was reduced by 0.79 (8.6 mmol/mol 95% confidence interval –1.10 to –0.49, −12.0 to −5.4 mmol/mol) and 0.92% (10.1 mmol/mol; –1.23 to –0.61, −13.4 to −6.7 mmol/mol) in the 20 and 30 mg groups, respectively, compared with placebo. Differences from placebo were statistically significant ( P < 0.0001), but the differences between the 20 and 30 mg groups were not. The intent‐to‐treat analysis yielded similar findings. Conclusions The HbA 1c was significantly and meaningfully reduced by both doses of PF‐734200, but 20 mg appears to be the more appropriate therapeutic dose for Type 2 diabetes mellitus, contingent upon confirmation by long‐term controlled studies.