RETRACTED: Evaluation of the positive effects on insulin-resistance and ß-cell measurements of vildagliptin in addition to metformin in type 2 diabetic patients.

We evaluated the positive effects of vildagliptin in addition to metformin on glycemic control and ß-cell function in type 2 diabetic patients. One hundred and seventy-one type 2 diabetic patients were instructed to add vildaglipin 50mg twice a day or placebo to metformin for 12 months. Body mass index (BMI), glycemic control, fasting plasma insulin (FPI), HOMA-IR, HOMA-ß, fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, vaspin, visfatin, and omentin-1 were evaluated. Before, and after 12 months since the addition of vildagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation. Vildagliptin+metformin were more effective than placebo+metformin in reducing body weight and BMI, glycemic control, HOMA-IR, glucagon and insulin resistance measurements. Vildagliptin+metformin gave also a better increase of HOMA-ß, and of all ß-cell parameters after the clamp. We also recorded a significant correlation between M value increase and the decrease of vaspin, visfatin, and omentin-1 obtained with vildagliptin+metformin. Vildagliptin, in addition to metformin, proved to be effective in improving ß-cell function and in reducing insulin resistance measurements.

Rosiglitazone therapy improves insulin resistance parameters in overweight and obese diabetic patients intolerant to metformin.

BACKGROUND: Few studies have directly compared rosiglitazone and metformin effects on adipocytokines. The aim was to observe the possible effects of rosiglitazone and metformin on glycemic control, insulin sensitivity, plasma leptin (pL), adiponectin (ADN), tumor necrosis factor-alpha (TNF-alpha), and resistin (R) in overweight and obese diabetic patients intolerant to metformin. METHODS: Six hundred and ninety-four consecutive overweight and obese type 2 diabetic patients were evaluated and 56 patients were intolerant to metformin at maximum dosage. We added rosiglitazone to metformin in these intolerant patients (RM) and we compared them with 61 patients treated with metformin (M) in a single-blind placebo-controlled trial. We evaluated body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), pL, ADN, TNF-alpha, and R at baseline and after 3 and 6 months. Furthermore, we calculated insulin resistance index (HOMA-index) using FPG and FPI. RESULTS: Glycated hemoglobin, FPG, FPI, and HOMA-index results were lower than baseline values in RM and M groups. Glycated hemoglobin and HOMA-index values were significantly lower in RM group compared to M group at 6 months. Plasma leptin, ADN, TNF-alpha, and R were significantly improved in RM group compared to M group at 6 months. CONCLUSIONS: No BMI change was observed, probably because rosiglitazone was added to metformin, that could mitigate the body increase of rosiglitazone. Rosiglitazone improved glycemic control and insulin resistance-correlated parameters when added to intolerant metformin patients. These data suggest that rosiglitazone may be the drug of choice for the treatment of overweight and obese type 2 diabetic patients.

Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha.

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.

Effects of 1 year of treatment with pioglitazone or rosiglitazone added to glimepiride on lipoprotein (a) and homocysteine concentrations in patients with type 2 diabetes mellitus and metabolic syndrome: a multicenter, randomized, double-blind, controlled clinical trial.

BACKGROUND: Although the metabolic effects of the thiazolidinediones have been well studied, there is a lack of comparative data on their effects on certain cardiovascular risk factors, such as elevated plasma levels of lipoprotein (a) (Lp[a]) and homocysteine (Hcy). OBJECTIVE: This study compared the effects of pioglitazone or rosiglitazone added to glimepiride on a range of lipid parameters, focusing on Lp(a) and Hcy, in patients with type 2 diabetes mellitus and the metabolic syndrome. METHODS: This was a multicenter, randomized, controlled, double-blind study in patients with type 2 diabetes and the metabolic syndrome (hypertension [>or=130/85 mm Hg]) and triglyceridemia (>or=150 mg/dL). In addition to glimepiride 4 mg/d, patients received pioglitazone 15 mg QD or rosiglitazone 4 mg QD for 1 year. The primary efficacy variables were change from baseline in body mass index (BMI), glycosylated hemoglobin (HbA(1c)), Lp(a), and Hey. Secondary efficacy measures were changes in fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) concentrations, fasting and postprandial insulin concentrations (FPI and PPI, respectively), the Homeostasis Model Assessment index, and the lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides). All these parameters were measured after a 12-hour fast every 3 months for 1 year. Tolerability was assessed based on reported adverse events and laboratory abnormalities at each study visit. RESULTS: Ninety-one white patients with type 2 diabetes and the metabolic syndrome were enrolled, and 87 completed the study (43 men, 44 women; mean [SD] age, 53 [6] years; mean weight, 68.4 [3.3] kg). Mean baseline values for BMI and HbA(1c) were 24.3 (0.8) kg/m(2) and 8.1 % (0.8 %), respectively. At the end of 1 year, both treatment groups had significant increases from baseline in BMI (4.9% glimepiride + pio glitazone, 6.2% glimepiride + rosiglitazone; P < 0.05). Glimepiride + pioglitazone was associated with the following percent improvements from baseline in measures of glycemic control: -17.1% in HbA(1c), -19.3% in FPG, -17.8% in PPG, -40.1% in FPI, and -22.6% in PPI (all, P < 0.01). The corresponding percent improvements from baseline with glimepiride + rosiglitazone were -16.3%, -19.9%, -15.0%, -44.8%, and -22.1% (all, P < 0.01). There were no significant differences between treatment groups in any of these parameters. The pioglitazone group had significant improvements from baseline in TC (-11.1%), LDL-C (-12.0%), HDL-C (15.0%), and triglycerides (-22.4%) [corrected] (all, P < 0.05), whereas the rosiglitazone group had significant increases in TC (14.9%), LDL-C (16.5%), and triglycerides (17.9%) (all, P < 0.05); the difference between pioglitazone and rosiglitazone was statistically significant (P < 0.05). The change from baseline in Lp(a) was significant in the pioglitazone group, both relative to baseline and compared with the rosiglitazone group (-19.7% vs 0.5%, respectively; P < 0.05 vs baseline and vs rosiglitazone). Changes from baseline in Hey were significant in both the pioglitazone and rosiglitazone groups (-20.2% and -25.0%, respectively; P < 0.05), with no significant difference between groups. Both treatments were well tolerated, and no patients had significant changes in transaminases. CONCLUSIONS: In these patients with type 2 diabetes and the metabolic syndrome, the combinations of glimepiride with pioglitazone and glimepiride with rosiglitazone produced significant improvements in measures of glycemic control, plasma lipids, and homocysteinemia. One year of treatment with the pioglitazone combination was associated with significantly reduced plasma Lp(a) levels compared with the rosiglitazone combination.

Synergistic effect of doxazosin and acarbose in improving metabolic control in patients with impaired glucose tolerance.

OBJECTIVE: The aim of this study was to evaluate if the expected improvement in glucose and lipid metabolism obtainable with doxazosin is or is not synergistic with standard antihyperglycaemic treatment using the alpha-glucosidase inhibitor acarbose. METHODS: Patients in this randomised, controlled, double-blind clinical trial were enrolled, evaluated and followed up at three Italian centres. We evaluated 107 patients (53 males and 54 females) with impaired glucose tolerance (IGT) as determined by oral glucose tolerance tests (OGTTs). All patients took a fixed dose of acarbose 150 mg/day for 3 months, after which they were titrated up to 300 mg/day for the next 3 months. In addition, patients were randomised to either placebo (53 patients: 27 males and 26 females, aged 50 +/- 4 [mean +/- SD] years) or doxazosin 4 mg/day (54 patients: 26 males and 28 females, aged 51 +/- 5 years) for the entire 6-month treatment period. Parameters evaluated during the 6-month treatment period included body mass index (BMI), glycaemic control (glycosylated haemoglobin [HbA(1c)], fasting plasma [FPG] and post-prandial plasma [PPG] glucose, fasting plasma [FPI] and post-prandial plasma [PPI] insulin levels, homeostasis model assessment [HOMA]-index [insulin resistance]), lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]), and systolic (SBP) and diastolic (DBP) blood pressure. RESULTS: Significant reductions in BMI, HbA(1c), FPG and PPG compared with baseline were observed after 6 months in both groups (p < 0.05). A significant decrease in FPI was obtained after 6 months (p < 0.05) in the doxazosin group compared with baseline, and this difference was also significant (p < 0.05) compared with the placebo group. Similarly, a significant decrease in HOMA-index was observed at 6 months (p < 0.05) compared with baseline in the doxazosin group, and this difference was also significant (p < 0.05) compared with the placebo group. Significant decreases in TC, LDL-C, HDL-C and TG (p < 0.05) were observed in the doxazosin group after 6 months compared with baseline values. Significant decreases in SBP and DBP were also observed at 3 months in the doxazosin group compared with baseline (p < 0.05), and these differences were significant (p < 0.05) compared with placebo. Furthermore, significant decreases in SBP and DBP were observed at 6 months (p < 0.01) in the doxazosin group compared with baseline, and these differences were also significant (p < 0.01) compared with placebo. All patients who completed an OGTT at 6 months (96 patients) were restored to normal glucose tolerance status. CONCLUSION: In patients with IGT, doxazosin given in combination with acarbose seemed to improve glycaemic and lipid control compared with placebo, with the benefits observed appearing to extend beyond those expected from improvements in blood pressure. Patients in this study also benefited from acarbose therapy, which restored all patients from IGT to normal glucose tolerance status.

A comparison of the effects of pioglitazone and rosiglitazone combined with glimepiride on prothrombotic state in type 2 diabetic patients with the metabolic syndrome.

OBJECTIVE: To compare the effects of glimepiride plus pioglitazone or plus rosiglitazone in diabetic patients with the metabolic syndrome on coagulation and fibrinolysis parameters. STUDY DESIGN AND METHODS: 91 type 2 diabetic patients with the metabolic syndrome participated. All patients took a fixed dose of glimepiride, 4 mg/day. We administered pioglitazone (15 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We compared body mass index (BMI), glycemic control, coagulation and fibrinolysis parameters, and heart rate (HR) during 12 months of this treatment. RESULTS: A total of 87 completed the study (pioglitazone n=45 or rosiglitazone n=42). Body mass index increased after 12 months compared to baseline (p<0.05) in both groups. A significant decrease in glycated haemoglobin (HbA(1c)) was observed after 9 (p<0.05), and 12 (p<0.01) months in both groups. After 9 and 12 months, mean fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were lower in both groups (p<0.05 and 0.01, respectively), as were fasting plasma insulin (FPI) and postprandial plasma insulin (PPI) (p<0.05 and p<0.01, respectively). An improvement in the homeostasis model assessment index (HOMA index) was seen at 9 and 12 months (p<0.05 and 0.01, respectively) compared to the baseline value in both groups. Plasminogen activator inhibitor 1 (PAI-1) was significant lower (p<0.05) in both groups after 12 months compared to the baseline values. No changes in tissue-plasminogen activator (t-PA) and fibrinogen (Fg) were seen during the study nor were there any changes in transaminases. CONCLUSIONS: We conclude that the addition of a thiazolinedione to glimepiride treatment in type 2 diabetic subjects with the metabolic syndrome is associated with a slight but significant reduction of PAI-1 value, related to a similar reduction in insulinresistance.

Effects of telmisartan compared with eprosartan on blood pressure control, glucose metabolism and lipid profile in hypertensive, type 2 diabetic patients: a randomized, double-blind, placebo-controlled 12-month study.

We evaluated the antihypertensive activity, glucose homeostasis and plasma lipid profile in patients with mild hypertension and type 2 diabetes mellitus treated by diet and exercise, and not in receipt of oral hyperglycemics, following 12-month treatment with either telmisartan or eprosartan. In this double-blind, placebo-controlled trial, 119 patients with mild essential hypertension (diastolic blood pressure [DBP] 91-104 mmHg) and type 2 diabetes were divided into three groups and randomized to receive once-daily telmisartan 40 mg, eprosartan 600 mg, or placebo for 12 months. At enrollment, patients were advised on diet (1,400-1,600 kcal/day) and exercise (physical aerobics on a bicycle for at least 30 min on 4 days each week). Compared with baseline, a significant reduction (p<0.01) in seated trough systolic blood pressure (SBP) was detected after 12-month treatment with either telmisartan or eprosartan. Seated trough DBP was also reduced by telmisartan (p<0.01) and eprosartan (p<0.05); the antihypertensive effect of telmisartan was significantly superior (p<0.05). No change in body mass index or glucose metabolism was observed with either active treatment, or with placebo. Telmisartan, but not eprosartan, significantly improved plasma total cholesterol (p<0.01), low-density lipoprotein cholesterol (p<0.01) and triglycerides (p<0.05) compared with eprosartan. In conclusion, 12-month telmisartan treatment produced a significantly greater reduction in DBP than eprosartan and significantly improved plasma lipids. The improvement could be due to varying pharmacokinetic/pharmacodynamic properties of telmisartan compared with eprosartan, even if it is not clear about the relationship between angiotensin-II receptor blockade and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition.

Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with glimepiride: a twelve-month, multicenter, double-blind, randomized, controlled, parallel-group trial.

BACKGROUND: Glimepiride is approved as monotherapy and in combination with metformin or with insulin, whereas the combination of glimepiride with other antihyperglycemic drugs is under investigation. OBJECTIVE: The aim of this study was to assess the differential effect on glucose and lipid variables and tolerability of the combination of glimepiride plus pioglitazone or rosiglitazone in patients with type 2 diabetes mellitus (DM) and metabolic syndrome. METHODS: This 12-month, multicenter, double-blind, randomized, controlled, parallel-group trial was conducted at 3 study sites in Italy. We assessed patients with type 2 DM (duration, > or =6 months) and with metabolic syndrome. All patients were required to have poor glycemic control with, or to have experienced > or =1 adverse effect (AE) with, diet and oral hypoglycemic agents such as sulfonylureas or metformin, both given up to the maximum tolerated dose. All patients received a fixed oral dose of glimepiride, 4 mg/d divided into 2 doses, self-administered for 12 months. Patients also were randomized to receive oral pioglitazone (15 mg once daily) (G + P group) or oral rosiglitazone (4 mg once daily) (G + R group), self-administered for 12 months. We assessed body mass index (BMI), glycemic control (glycosylated hemoglobin [HbA(1c)], fasting and postprandial plasma glucose and insulin levels [FPG, PPG, FPI, and PPI, respectively], and homeostasis model assessment index), lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]), and lipoprotein variables (apolipoprotein [apo] A-I and apo B) at baseline and at 3, 6, 9, and 12 months of treatment. Treatment tolerability was assessed at each study visit using a thorough interview of patients, and comparisons of clinical and laboratory values to baseline levels. RESULTS: A total of 91 patients were enrolled in the study; 87 patients completed it (G + P group: 24 women, 21 men; mean [SD] age, 53 [6] years; G + R group: 20 women, 22 men; mean [SD] age, 54 [5] years). Patients in the G + P and G + R groups experienced significant increases in mean BMI at 12 months compared with baseline (4.92% and 6.17%, respectively; both, P < 0.05). The combination of glimepiride with pioglitazone or rosiglitazone significantly improved glycemic control in the study patients. At 12 months, we observed a 1.3% improvement in mean values for plasma HbA(1c) concentration (P < 0.01) 19.3% in FPG (P < 0.01), 16.3% in PPG (P < 0.01), 42.4% in FPI ), and 23.3% in PPI (P <0.05); no significant differences were found between treatment groups. Although the G + P group experienced a significant improvement at 12 months in almost all variables of lipid metabolism from baseline (TC, - 11%; LDL-C, -12%; HDL-C, 15%; and apo B, - 10.6% [all, P , 0.05]), the G + R group experienced a significant increase in mostly the lipid risk factors for cardiovascular disease (TC, 14.9%; LDL-C, 16.5%; TG, 17.9%; and apo B, 10.3% [all, P , 0.05]). Overall, no statistically significant changes in plasma aminotransferase activities were observed. Of the 87 patients who completed the study, 6.7% (3/45) of patients in the G + P group and 11.9% (5/42) of patients in the G + R group had transient, mild to moderate AEs that did not cause withdrawal from the trial. CONCLUSION: In this study of patients with type 2 DM and metabolic syndrome who did not respond adequately to, or experienced AEs with, diet and either a sulfonylurea or metformin previously, the combination of glimepiride plus pioglitazone was associated with a significant improvement in lipid and lipoprotein variables, whereas the combination of glimepiride plus rosiglitazone appears to not have had any clinically significant effect on lipid metabolism.

Vildagliptin added to metformin on ß-cell function after a euglycemic hyperinsulinemic and hyperglycemic clamp in type 2 diabetes patients.

BACKGROUND: This study evaluated the effect of vildagliptin + metformin on glycemic control and ß-cell function in type 2 diabetes patients. SUBJECTS AND METHODS: One hundred seventy-one type 2 diabetes patients, naive to antidiabetes therapy and with poor glycemic control, were instructed to take metformin for 8±2 months up to a mean dosage of 2,500±500 mg/day; then they were randomly assigned to add vildaglipin 50 mg twice a day or placebo for 12 months. We evaluated at 3, 6, 9, and 12 months: body mass index, glycemic control, fasting plasma insulin, homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment ß-cell function index (HOMA-ß), fasting plasma proinsulin, proinsulin/fasting plasma insulin ratio, C-peptide, glucagon, adiponectin, and high-sensitivity C-reactive protein. Before and at 12 months after the addition of vildagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation, to assess insulin sensitivity and insulin secretion. RESULTS: After 12 months of treatment, vildagliptin + metformin gave a better decrease of body weight, glycemic control, HOMA-IR, and glucagon and a better increase of HOMA-ß compared with placebo + metformin. Regarding the measures of ß-cell function, treatment-induced changes in M-value, first- and second-phase C-peptide response to glucose, and C-peptide response to arginine were significantly higher in the vildagliptin + metformin group compared with the placebo + metformin group. CONCLUSION: The addition of vildagliptin to metformin gave a better improvement of glycemic control, insulin resistance, and ß-cell function compared with metformin alone.

Vildagliptin action on some adipocytokine levels in type 2 diabetic patients: a 12-month, placebo-controlled study.

OBJECTIVE: To evaluate the action of vildagliptin + metformin on some adipocytokine levels, glycemic control, and ß-cell function in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 171 patients with poor glycemic control were instructed to add after a 8 ± 2 month-run-in period with metformin, vildagliptin 50 mg twice a day or placebo for 12 months. MAIN OUTCOME MEASURES: We evaluated at 3, 6, 9, and 12 months, the body mass index (BMI), glycemic control, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment ß-cell function index (HOMA-ß), fasting plasma proinsulin (FPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, resistin, retinol-binding protein-4 (RBP-4), chemerin, and tumor necrosis factor-α (TNF-α). Patients also underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation to assess insulin sensitivity and insulin secretion. RESULTS: After 12 months of vildagliptin + metformin, we observed a better decrease of body weight, glycemic control, HOMA-IR, and glucagon, and a better increase of HOMA-ß, and of all the measures of ß-cell function, compared to placebo + metformin. Vildagliptin + metformin also decreased resistin, RBP-4, and chemerin better. CONCLUSION: Vildagliptin seems to have a positive action on some adipocytokines related to inflammation.

Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.

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.