Efficacy and safety of the dipeptidyl peptidase-4 inhibitor PF-734200 added to metformin in Type 2 diabetes.

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.

• Authors: J Rosenstock, A J Lewin, P Norwood, V Somayaji, T T Nguyen, J G Teeter, S L Johnson, H Dai, S G Terra
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 28 Issue 4 Pg. 464-9 (Apr 2011) ISSN: 1464-5491 [Electronic] England
• PMID: 21392067 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Hypoglycemic Agents
• Pyrimidines
• Pyrrolidines
• Metformin
• gosogliptin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Diabetes Mellitus, Type 2 (drug therapy)
• Dipeptidyl-Peptidase IV Inhibitors (administration & dosage, pharmacology)
• Drug Therapy, Combination
• Epidemiologic Methods
• Female
• Humans
• Hypoglycemic Agents (administration & dosage, pharmacology)
• Male
• Metformin (administration & dosage, pharmacology)
• Middle Aged
• Pyrimidines (administration & dosage, pharmacology)
• Pyrrolidines (administration & dosage, pharmacology)
• Treatment Outcome
• Young Adult