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The dipeptidyl peptidase-4 inhibitor PHX1149 improves blood glucose control in patients with type 2 diabetes mellitus . AIM To determine the efficacy and tolerability of PHX1149 , a novel dipeptidyl peptidase-4 ( DPP4 ) inhibitor , in patients with type 2 diabetes . METHODS This is a multicentre , randomized , double-blind , placebo-controlled , 4-week study in patients with type 2 diabetes with suboptimal metabolic control . Patients with a baseline haemoglobin A ( 1c ) ( HbA ( 1c ) ) of 7.3 to 11.0 % were randomized 1 : 1 : 1 : 1 to receive once-daily oral therapy with either PHX1149 ( 100 , 200 or 400 mg ) or placebo ; patients were on a constant background therapy of either metformin alone or metformin plus a glitazone . RESULTS Treatment with 100 , 200 or 400 mg of PHX1149 significantly decreased postprandial glucose area under the curve AUC ( 0-2 h ) by approximately 20 % ( +0.11 +/- 0.50 , -2.08 +/- 0.51 , -1.73 +/- 0.49 and -1.88 +/- 0.48 mmol/l x h , respectively , for placebo and 100 , 200 and 400 mg ( p = 0.002 , 0.008 and 0.004 vs. placebo ) . Postprandial AUC ( 0-2 h ) of intact glucagon-like peptide-1 , the principal mediator of the biological effects of DPP4 inhibitors , was increased by 3.90 +/- 2.83 , 11.63 +/- 2.86 , 16.42 +/- 2.72 and 15.75 +/- 2.71 pmol/l x h , respectively , for placebo and 100 , 200 and 400 mg ( p = 0.053 , 0.001 and 0.002 vs. placebo ) . Mean HbA ( 1c ) was lower in all dose groups ; the placebo-corrected change in the groups receiving 400 mg PHX1149 was -0.28 % ( p = 0.02 ) . DPP4 inhibition on day 28 was 53 , 73 and 78 % at 24 h postdose in the groups receiving 100 , 200 and 400 mg PHX1149 , respectively . There were no differences in adverse events between PHX1149-treated and placebo subjects . CONCLUSIONS Addition of the DPP4 inhibitor PHX1149 to a stable regimen of metformin or metformin plus a glitazone in patients with type 2 diabetes was well tolerated and improved blood glucose control .
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Intervention_Pharmacological
dipeptidyl peptidase-4 inhibitor PHX1149
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Intervention_Pharmacological
PHX1149
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Intervention_Pharmacological
PHX1149 ( 100 , 200 or 400 mg )
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Intervention_Control
placebo
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Outcome_Physical
blood glucose control
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Outcome_Other
efficacy and tolerability
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Outcome_Physical
postprandial glucose area under the curve AUC ( 0-2
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Outcome_Physical
Postprandial AUC ( 0-2 h ) of intact glucagon-like peptide-1
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Outcome_Physical
Mean HbA ( 1c )
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Outcome_Physical
DPP4 inhibition
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Outcome_Adverse-effects
adverse events
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Outcome_Other
well tolerated
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Outcome_Physical
improved blood glucose control .
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Participant_Condition
type 2 diabetes mellitus
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Participant_Condition
type 2 diabetes
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Participant_Condition
type 2 diabetes with suboptimal metabolic control
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Participant_Condition
baseline haemoglobin A ( 1c ) ( HbA ( 1c ) ) of 7.3 to 11.0 %
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Participant_Condition
type 2 diabetes