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.
Copyright 2010 Elsevier Inc. All rights reserved.