Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes.
OBJECTIVE
The aim of this study was to compare efficacy and tolerability of initial combination therapy with vildagliptin/pioglitazone to component monotherapy.


METHODS
This 24-week, multicentre, randomized, double-blind, active-controlled study assessed the effects of the dipeptidyl peptidase-4 inhibitor vildagliptin (100 mg q.d.), pioglitazone (30 mg q.d.) and vildagliptin combined with pioglitazone (100/30 mg q.d. or 50/15 mg q.d.) in 607 drug-naive patients with type 2 diabetes (T2DM). The primary outcome measure was change from baseline in HbA(1c) in patients receiving initial combination therapy compared with pioglitazone monotherapy.


RESULTS
After 24-week treatment, adjusted mean changes in HbA(1c) from baseline (approximately 8.7%) in patients receiving pioglitazone monotherapy, 50/15 mg combination, 100/30 mg combination and vildagliptin monotherapy were -1.4 +/- 0.1%, -1.7 +/- 0.1%, -1.9 +/- 0.1% and -1.1 +/- 0.1% respectively. Both low-dose and high-dose combinations were significantly more efficacious than pioglitazone alone (p = 0.039 and p < 0.001 respectively). Adjusted mean changes in fasting plasma glucose were -1.9 +/- 0.2, -2.4 +/- 0.2, -2.8 +/- 0.2 and -1.3 +/- 0.2 mmol/l respectively, and both combination groups were significantly more effective than pioglitazone monotherapy (p = 0.022 and p < 0.001 respectively). The overall incidence of adverse events ranged from 45.8% in the low-dose combination to 51.6% in the pioglitazone monotherapy group. The incidence of peripheral oedema was highest in patients receiving pioglitazone monotherapy (9.3%) and lowest in those receiving low-dose combination (3.5%). One mild hypoglycaemic event was reported by one patient receiving high-dose combination and one patient receiving vildagliptin monotherapy.


CONCLUSIONS
First-line treatment with vildagliptin/pioglitazone combination in patients with T2DM provides better glycaemic control than either monotherapy component yet has minimal risk of hypoglycaemia and a tolerability profile comparable with component monotherapy.
Rosenstock
J
J
Dallas Diabetes and Endocrine Center, Dallas, TX, USA.
Kim
S W
SW
Baron
M A
MA
Camisasca
R-P
RP
Cressier
F
F
Couturier
A
A
Dejager
S
S
D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D000077205:Pioglitazone; D011480:Protease Inhibitors / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077597:Vildagliptin
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D008055:Lipids; D009570:Nitriles; D011480:Protease Inhibitors; D011759:Pyrrolidines; D045162:Thiazolidinediones; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane; D000077205:Pioglitazone