Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study.
OBJECTIVE
To evaluate the efficacy and safety of alogliptin in patients with type 2 diabetes inadequately controlled by therapy with a thiazolidinedione (TZD).


METHODS
In a multicenter, double-blind, placebo-controlled clinical study, 493 patients 18-80 years old with inadequate glycemic control after stabilization (i.e., glycosylated hemoglobin [HbA(1c)] 7.0-10.0%) despite ongoing treatment with a TZD were randomly assigned (2:2:1) to treatment with pioglitazone plus alogliptin 12.5 mg, alogliptin 25 mg or placebo once daily. Concomitant therapy with metformin or sulfonylurea at prestudy doses was permitted.


METHODS
The primary efficacy endpoint was change in HbA(1c) from baseline to Week 26. Secondary endpoints included changes in fasting plasma glucose (FPG) and body weight, and incidences of marked hyperglycemia (FPG > or = 200 mg/dL [11.10 mmol/L]) and rescue for hyperglycemia.


RESULTS
Least squares (LS) mean change in HbA(1c) was significantly (p < 0.001) greater for alogliptin 12.5 mg (-0.66%) or 25 mg (-0.80%) than for placebo (-0.19%). A significantly (p < or = 0.016) larger proportion of patients achieved HbA(1c) < or = 7% with alogliptin 12.5 mg (44.2%) or 25 mg (49.2%) than with placebo (34.0%). LS mean decreases in FPG were significantly (p = 0.003) greater with alogliptin 12.5 mg (-19.7 mg/dL [-1.09 mmol/L]) or 25 mg (-19.9 mg/dL [-1.10 mmol/L]) than with placebo (-5.7 mg/dL [-0.32 mmol/L]). The percentage of patients with marked hyperglycemia was significantly (p < 0.001) lower for alogliptin (< or =25.0%) than placebo (44.3%). The incidences of overall adverse events and hypoglycemia were similar across treatment groups, but cardiac events occurred more often with active treatment than placebo.


CONCLUSIONS
Addition of alogliptin to pioglitazone therapy significantly improved glycemic control in patients with type 2 diabetes and was generally well tolerated. The study did not evaluate the effect of combination therapy on long-term clinical outcomes and safety.


BACKGROUND
NCT00286494, clinicaltrials.gov.
Pratley
Richard E
RE
Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Given C331, 89 Beaumont Avenue, Burlington, VT 05405, USA. Richard.Pratley@uvm.edu
Reusch
Jane E -B
JE
Fleck
Penny R
PR
Wilson
Craig A
CA
Mekki
Qais
Q
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D010880:Piperidines; D010919:Placebos; D045162:Thiazolidinediones; D014498:Uracil; C520853:alogliptin