Michelle A. Baron

Comparison of Vildagliptin and Rosiglitazone Monotherapy in Patients With Type 2 Diabetes: A 24-week, double-blind, randomized trial

OBJECTIVE—To compare the efficacy and tolerability of vildagliptin and rosiglitazone during a 24-week treatment in drug-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—This was a double-blind, randomized, active-controlled, parallel-group, multicenter study of 24-week treatment with vildagliptin (100 mg daily, given as equally divided doses; n = 519) or rosiglitazone (8 mg daily, given as a once-daily dose; n = 267). RESULTS—Monotherapy with vildagliptin and rosiglitazone decreased A1C (baseline = 8.7%) to a similar extent during the 24-week treatment, with most of the A1C reduction achieved by weeks 12 and 16, respectively. At end point, vildagliptin was as effective as rosiglitazone, improving A1C by −1.1 ± 0.1% (P < 0.001) and −1.3 ± 0.1% (P < 0.001), respectively, meeting the statistical criterion for noninferiority (upper-limit 95% CI for between-treatment difference ≤0.4%). Fasting plasma glucose decreased more with rosiglitazone (−2.3 mmol/l) than with vildagliptin (−1.3 mmol/l). Body weight did not change in vildagliptin-treated patients (−0.3 ± 0.2 kg) but increased in rosiglitazone-treated patients (+1.6 ± 0.3 kg, P < 0.001 vs. vildagliptin). Relative to rosiglitazone, vildagliptin significantly decreased triglycerides, total cholesterol, and LDL, non-HDL, and total-to-HDL cholesterol (−9 to −16%, all P ≤ 0.01) but produced a smaller increase in HDL cholesterol (+4 vs. +9%, P = 0.003). The proportion of patients experiencing an adverse event was 61.4 vs. 64.0% in patients receiving vildagliptin and rosiglitazone, respectively. Only one mild hypoglycemic episode was experienced by one patient in each treatment group, while the incidence of edema was greater with rosiglitazone (4.1%) than vildagliptin (2.1%). CONCLUSIONS—Vildagliptin is an effective and well-tolerated treatment option in patients with type 2 diabetes, demonstrating similar glycemic reductions as rosiglitazone but without weight gain.

Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled study*

Aim:  The purpose of this study was to assess the efficacy and tolerability of the dipeptidyl peptidase‐4 inhibitor vildagliptin in combination with the thiazolidinedione (TZD) pioglitazone in patients with type 2 diabetes (T2DM).

Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes

Aim:  The aim of this study was to compare efficacy and tolerability of initial combination therapy with vildagliptin/pioglitazone to component monotherapy.

Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea

Aim:  To compare the efficacy and tolerability of vildagliptin vs. placebo in patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled [haemoglobin A1c (HbA1c) 7.5 to 11%] with prior sulphonylurea (SU) monotherapy.

Continuous subcutaneous delivery of exenatide via ITCA 650 leads to sustained glycemic control and weight loss for 48 weeks in metformin-treated subjects with type 2 diabetes

AIMS Evaluate the efficacy and tolerability of ITCA 650 in subjects with type 2 diabetes treated for up to 48 weeks. METHODS This was a 24-week extension to a randomized, 24-week, open-label, phase 2 study in subjects with type 2 diabetes inadequately controlled with metformin. Subjects received ITCA 650 mg (20, 40, 60 or 80 μg/day). Mean changes for HbA1c, weight, and fasting plasma glucose (FPG) were evaluated. RESULTS Mean changes in HbA1c from baseline to week 48 ranged from -0.85% to -1.51%. At week 48, ≥64% of subjects with an HbA1c ≤7% at week 24 maintained an HbA1c ≤7%. The incidence of adverse events (AEs) was dose-related and ranged from 13.3% with 20 μg/day to 37.5% with 80 μg/day. Most AEs were mild and transient; the incidence of nausea declined from 12.9% to 9.5% over the 24-week extension. One subject on ITCA 650 80 μg/day experienced mild intermittent vomiting. Three (3.5%) subjects experienced severe AEs, but none were considered related to study drug. CONCLUSION Significant changes in HbA1c, body weight, and FPG attained with ITCA 650 were maintained to 48 weeks. The incidence of AEs was lower in the 24-week extension than in the initial 24-week treatment phase.

Comparison of vildagliptin and thiazolidinedione as add-on therapy in patients inadequately controlled with metformin: results of the GALIANT trial--a primary care, type 2 diabetes study.

Aim: To assess the efficacy and tolerability of vildagliptin compared with thiazolidinediones (TZDs) as an add on to metformin treatment in a primary care patient population with type 2 diabetes.

Impact of comorbid conditions and race/ethnicity on glycemic control among the US population with type 2 diabetes, 1988–1994 to 1999–2004

OBJECTIVE To measure trends in glycemic control in type 2 diabetes in the United States from 1988-1994 to 1999-2004 and to identify factors influencing glycemic control, including the presence of comorbid conditions and race/ethnicity. METHODS Participants in the National Health and Nutrition Examination Surveys (1988-1994 and 1999-2004) aged ≥30 years with diagnosed type 2 diabetes were identified. Outcome measures included glycemic control [glycosylated hemoglobin (A1C) <7%] and pharmacologic treatment rate. Comorbid conditions assessed included obesity, hyperlipidemia, and hypertension. RESULTS Prevalence of type 2 diabetes increased from 5.8% in 1988-1994 to 7.1% in 1999-2004. Rates of treatment for type 2 diabetes improved, from 72.3% to 82.2%. The proportion of patients who achieved A1C <7% did not change significantly (44.4% to 50.1%, P=.06); however, blood pressure and cholesterol level both improved. During 1999-2004, only 14% of persons treated for type 2 diabetes did not have an additional comorbid condition; 21% had all three comorbid conditions. During 1999-2004, among treated patients, non-Hispanic blacks were 0.43 times as likely (95% CI 0.29-0.63), and Mexican Americans were 0.47 times as likely (95% CI 0.32-0.68), to have A1C <7% compared to non-Hispanic whites. CONCLUSIONS Despite improved treatment rates, one in two individuals with type 2 diabetes has A1C of ≥7%. Most type 2 diabetic subjects also suffer from hypertension, hyperlipidemia, and/or obesity, and glycemic control rates were lowest for those with all three conditions. Non-Hispanic blacks and Mexican Americans are less likely to achieve glycemic control as compared to non-Hispanic whites.

Efficacy and tolerability of initial combination therapy with nateglinide and metformin in treatment-naïve patients with type 2 diabetes

SUMMARY Objective: To assess the efficacy and tolerability of the combination of nateglinide (120 mg, ac) and metformin (500 mg, tid) as initial treatment in drug-naïve patients with type 2 diabetes mellitus (T2DM). Research design and methods: This study reports data from the treatment-naïve (TN) subgroup of patients in a previously published, randomized, multicenter, placebo-controlled, 24-week trial that compared nateglinide, metformin, and the combination therapy (CT) in 701 patients with T2DM with baseline HbA1c between 6.8% and 11.0%. Of the 401 TN patients, 104, 104, 89, and 104 patients received nateglinide (120 mg, ac), metformin (500 mg, tid), CT, and placebo, respectively. The baseline characteristics of each group were similar, with mean age, BMI, duration of diabetes, HbA1c, and fasting plasma glucose (FPG) levels of approximately 58 years, 30 kg/m2, 4 years, 8.2%, and 10.2 mmol/L, respectively. Results: In patients receiving initial CT, HbA1c decreased substantially (▵ = –1.6 ± 0.1%, p < 0.0001 vs. baseline or placebo) from a mean baseline of 8.2 ± 0.1%, an effect significantly greater than the 0.8% reduction observed with both monotherapies ( p < 0.001); whereas, in placebo-treated patients, HbA1c increased modestly (▵ = +0.3 ± 0.1%, p < 0.05) from an identical baseline value. Seventy percent of CT-treated patients achieved a target HbA1c of < 7.0%. Both fasting plasma glucose (FPG) and the 2-hour postprandial glucose excursion (PPGE) after a liquid meal challenge decreased by 2.3 mmol/L in patients receiving CT, while the changes from baseline values in FPG and PPGE were +0.2 ± 0.3 mmol/L and –0.5 ± 0.2 mmol/L, respectively, in placebo-treated patients. The incremental 30-minute post-load insulin levels increased by 88 ± 32 pmol/L ( p = 0.006) in patients receiving CT and did not change significantly in placebo-treated patients. Gastrointestinal side effects occurred in 27% of patients receiving CT (vs. 27.9% in the metformin monotherapy, and 14.4% in the placebo groups). Confirmed hypoglycemia (glucose ≤ 2.8 mmol/L) occurred in 3.4% of patients receiving CT. Conclusions: Initial CT with the rapid-acting insulinotropic agent, nateglinide, and metformin, an agent with insulin-sensitizing effects in the liver and periphery, is a safe and effective means of achieving glycemic targets in TN patients with T2DM.

Randomized Trial of Continuous Subcutaneous Delivery of Exenatide by ITCA 650 Versus Twice-Daily Exenatide Injections in Metformin-Treated Type 2 Diabetes

OBJECTIVE To evaluate ITCA 650, a continuous subcutaneous miniature osmotic pump delivery system of exenatide versus twice-daily exenatide injections (Ex-BID) in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a randomized, two-stage, 24-week, open-label, phase 2 study in type 2 diabetes inadequately controlled with metformin. Stage I: 155 subjects were randomized to 20 or 40 μg/day of ITCA 650 or Ex-BID 5→10 μg. Stage II: 131 subjects were rerandomized to 20, 40, 60, or 80 μg/day of ITCA 650. Change from baseline for HbA1c, weight, and fasting plasma glucose were evaluated at weeks 12 and 24. RESULTS HbA1c was significantly lower in all groups after 12 and 24 weeks. Stage I: mean change in HbA1c from a mean baseline of 7.9–8.0% was −0.98, −0.95, and −0.72% for the 20 and 40 μg/day ITCA 650 and Ex-BID groups, respectively, with 63, 65, and 50% of subjects achieving HbA1c levels ≤7% (P < 0.05). Stage II: significant (P < 0.05) reductions in HbA1c (∼1.4% from baseline) were achieved with 60 and 80 μg/day ITCA 650, and 86 and 78% of subjects achieved HbA1c ≤7% at 24 weeks; respectively. Weight was reduced by 2.8–3.7 kg (P < 0.05) at 24 weeks in all except the 20→20 μg/day group. ITCA 650 was well tolerated; nausea was lower and transient with 20 μg/day relative to Ex-BID; and 60 μg/day had the best profile of tolerability and HbA1c lowering. CONCLUSIONS ITCA 650 significantly reduced HbA1c and weight and was well tolerated. The 20→60 μg/day regimen was considered the best dose for further examination in phase 3.

Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-naïve elderly patients with type 2 diabetes

Aim:  The aim of this work was to assess the efficacy and tolerability of nateglinide alone or in combination with metformin in elderly patients with type 2 diabetes (T2DM).