The aim of the study was to compare the effects of the addition of
sitagliptin or
metformin to
pioglitazone monotherapy in poorly controlled
type 2 diabetes mellitus patients on
body weight,
glycemic control, beta-cell function,
insulin resistance, and inflammatory state parameters. One hundred fifty-one patients with uncontrolled
type 2 diabetes mellitus (
glycated hemoglobin [HbA(1c)] >7.5%) in
therapy with
pioglitazone 30 mg/d were enrolled in this study. We randomized patients to take
pioglitazone 30 mg plus
sitagliptin 100 mg once a day, or
pioglitazone 15 mg plus
metformin 850 mg twice a day. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters:
body weight, body mass index, HbA(1c), fasting plasma
glucose (FPG), postprandial plasma
glucose (PPG), fasting plasma
insulin (FPI), homeostasis model assessment
insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell function index, fasting plasma
proinsulin (Pr), Pr/FPI ratio,
adiponectin,
resistin (R),
tumor necrosis factor-alpha (
TNF-alpha), and
high-sensitivity C-reactive protein. A decrease of
body weight and body mass index was observed with
metformin, but not with
sitagliptin, at the end of the study. We observed a comparable significant decrease of HbA(1c), FPG, and PPG and a significant increase of homeostasis model assessment beta-cell function index compared with baseline in both groups without any significant differences between the 2 groups. Fasting plasma
insulin, fasting plasma Pr, Pr/FPI ratio, and HOMA-IR values were decreased in both groups even if the values obtained with
metformin were significantly lower than the values obtained with
sitagliptin. There were no significant variations of ADN, R, or
TNF-alpha with
sitagliptin, whereas a significant increase of ADN and a significant decrease of R and
TNF-alpha values were recorded with
metformin. A significant decrease of
high-sensitivity C-reactive protein value was obtained in both groups without any significant differences between the 2 groups. There was a significant correlation between HOMA-IR decrease and ADN increase, and between HOMA-IR decrease and R and
TNF-alpha decrease in
pioglitazone plus
metformin group after the treatment. The addition of both
sitagliptin or
metformin to
pioglitazone gave an improvement of HbA(1c), FPG, and PPG; but
metformin led also to a decrease of
body weight and to a faster and better improvement of
insulin resistance and inflammatory state parameters, even if
sitagliptin produced a better protection of beta-cell function.