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

Abstract

. 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.

Trial registration: ClinicalTrials.gov NCT00727857.

© 2010 Wiley Periodicals, Inc.

Figures

Figure 1

Mean changes from baseline in lipid fractionations. Baseline low‐density lipoprotein (LDL) particle concentration for pioglitazone/metformin fixed‐dose combination (FDC), pioglitazone, and metformin were 1460.9 nmol/L, 1517.1 nmol/L, and 1471.2 nmol/L, respectively. Baseline LDL particle size were 20.28 nm, 20.31 nm, and 20.35 nm, respectively. ***P<.0001 vs pioglitazone fdc therapy. monotherapy. se indicates standard error of the mean.>

Figure 2

Mean change from baseline in large and small low‐density lipoprotein (LDL) particle concentration. Baseline LDL small particle concentrations for pioglitazone/metformin fixed‐dose combination (FDC), pioglitazone, and metformin were 1127.8 nmol/L, 1163.9 nmol/L, and 1110.7 nmol/L, respectively. Baseline LDL large particle concentrations were 256.5 nmol/L, 271.1 nmol/L, and 287.3 nmol/L, respectively. *P<.001 and vs pioglitazone fdc therapy monotherapy. se indicates standard error of the mean.>

Figure 3

Median percentage changes from baseline in high‐sensitivity C‐reactive protein (hs‐CRP). Baseline median level hs‐CRP for pioglitazone/metformin fixed‐dose combination (FDC), pioglitazone, and metformin were 3.55 mg/L, 2.89 mg/L, and 3.08 mg/L, respectively. †P<.01 vs pioglitazone monotherapy fdc therapy therapy. et indicates early termination.>

Figure 4

Mean changes from baseline in adiponectin. Baseline adiponectin for pioglitazone/metformin fixed‐dose combination (FDC), pioglitazone, and metformin were 6.1 μg/mL, 6.8 μg/mL, and 7.2 μg/mL, respectively. *P<.0001 vs pioglitazone fdc therapy and monotherapy. se indicates standard error of the mean et early termination.>