Effects of pioglitazone and metformin fixed-dose combination therapy on
cardiovascular risk markers of inflammation and lipid profile compared with
pioglitazone and metformin monotherapy in patients with type 2 diabetes.
Author(s): Perez A, Jacks R, Arora V, Spanheimer R.
Affiliation(s): Takeda Global Research and Development Center, Inc, Deerfield, IL, USA.
Publication date & source: 2010, J Clin Hypertens (Greenwich). , 12(12):973-82
. Type 2 diabetes mellitus (T2DM) treatment should not increase cardiovascular
(CV) risk and at best could provide benefit beyond lowering glucose. Pioglitazone
has demonstrated a favorable CV profile relative to other oral antidiabetic drugs
(OADs) in outcome and observational studies. This randomized, double-blind,
parallel-group controlled study examined circulating biomarkers of CV risk in
T2DM patients receiving a fixed-dose combination (FDC) of pioglitazone/metformin
compared with the respective monotherapies. Patients with stable glycosylated
hemoglobin (HbA(1c) ) for 3 months taking no OADs were treated with pioglitazone
15mg/metformin 850mg FDC twice daily (bid), pioglitazone 15mg bid, or metformin
850mg bid for 24 weeks. FDC and pioglitazone increased high-density lipoprotein
cholesterol by 14.20% and 9.88%, respectively, vs an increase of 6.09% with
metformin (P<.05, metformin vs FDC). Triglycerides decreased with all three
treatments -5.95%, -5.54% and -1.78%, respectively; P=not significant). FDC and
pioglitazone significantly decreased small low-density lipoprotein and increased
large low-density lipoprotein particle concentrations. Reductions in
high-sensitivity C-reactive protein were greater in the FDC and pioglitazone
groups. Increases in adiponectin were significant in the FDC and pioglitazone
groups (P<.0001 vs metformin). Overall, adverse events were not higher with the
FDC. Thus, treatment with the FDC resulted in improved levels of CV biomarkers,
which were better than or equal to monotherapy.