S. Dejager

Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial

Aims:  The study evaluated the efficacy and tolerability of the dipeptidyl peptidase‐4 inhibitor, vildagliptin, and metformin in drug‐naïve elderly patients with type 2 diabetes. The primary objective was to demonstrate non‐inferiority of vildagliptin vs. metformin in glycated haemoglobin (HbA1c) reduction.

Mild to Moderate Muscular Symptoms with High-Dosage Statin Therapy in Hyperlipidemic Patients —The PRIMO Study

SummaryObjectives: To characterize the risk factors, rate of occurrence, onset, nature and impact of mild to moderate muscular symptoms with high-dosage HMG-CoA reductase inhibitor (statin) therapy in general practice.Methods: The Prédiction du Risque Musculaire en Observationnel (Prediction of Muscular Risk in Observational conditions, PRIMO) survey was an observational study of muscular symptoms in an unselected population of 7924 hyperlipidemic patients receiving high-dosage statin therapy in a usual care, outpatient setting in France. Information on patient demographics, treatment history and muscular symptoms was obtained by question-naires.Results: Multivariate analysis revealed the strongest predictors for muscular symptoms to be a personal history of muscle pain during lipid-lowering therapy (odds ratio, OR, 10.12, 95% CI 8.23–12.45; P < 0.0001), unexplained cramps (OR 4.14; 95% CI 3.46–4.95; P < 0.0001) and a history of creatine kinase (CK) elevation (OR 2.04; 95% CI 1.55–2.68; P < 0.0001). Overall, muscular symptoms were reported by 832 patients (10.5%), with a median time of onset of 1 month following initiation of statin therapy. Muscular pain prevented even moderate exertion during everyday activities in 315 patients (38%), while 31 (4%) were confined to bed or unable to work. Fluvastatin XL was associated with the lowest rate of muscular symptoms (5.1%) among individual statins.Conclusion: PRIMO demonstrated that mild to moderate muscular symptoms with high-dosage statin therapy may be more common and exert a greater impact on everyday lives than previously thought. Knowledge of the risk factors for muscular symptoms will allow identification and improved management of high-risk patients. The risk of muscular symptoms with fluvastatin XL treatment may be lower than with high dosages of other statins.

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.

Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy

Aim:  To examine the efficacy and safety of vildagliptin vs. glimepiride as add‐on therapy to metformin in patients with type 2 diabetes mellitus in a 52‐week interim analysis of a large, randomized, double‐blind, multicentre study. The primary objective was to demonstrate non‐inferiority of vildagliptin vs. glimepiride in glycosylated haemoglobin (HbA1c) reduction at week 52.

Comparison between vildagliptin and metformin to sustain reductions in HbA1c over 1 year in drug-naïve patients with Type 2 diabetes

Aims  To evaluate the ability of vildagliptin and metformin to sustain reductions in HbA1c over a 1‐year treatment period in drug‐naïve patients with Type 2 diabetes (Type 2 DM).

Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study

Aim: To show that vildagliptin added to metformin is non‐inferior to glimepiride in reducing HbA1c levels from baseline over 2 years.

Vildagliptin Enhances Islet Responsiveness to Both Hyper- and Hypoglycemia in Patients with Type 2 Diabetes

CONTEXT Dipeptidyl peptidase-4 inhibitors act by increasing plasma levels of glucagon-like peptide-1 and suppressing excessive glucagon secretion in patients with type 2 diabetes. However, their effects on the glucagon response to hypoglycemia are not established. OBJECTIVE The aim of the study was to assess effects of the dipeptidyl peptidase-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia. DESIGN We conducted a single-center, randomized, double-blind, placebo-controlled, two-period crossover study of 28-d treatment, with a 4-wk between-period washout. PATIENTS We studied drug-naive patients with type 2 diabetes and baseline glycosylated hemoglobin of 7.5% or less. INTERVENTION Participants received vildagliptin (100 mg/d) or placebo as outpatients. PRIMARY OUTCOME MEASURE(S): We measured the following: 1) change in plasma glucagon levels during hypoglycemic (2.5 mm glucose) clamp; and 2) incremental (Delta) glucagon area under the concentration-time curve from time 0 to 60 min (AUC(0-60 min)) during standard meal test. Before the study, it was hypothesized that vildagliptin would suppress glucagon secretion during meal tests and enhance the glucagon response to hypoglycemia. RESULTS The mean change in glucagon during hypoglycemic clamp was 46.7 +/- 6.9 ng/liter with vildagliptin treatment and 33.9 +/- 6.7 ng/liter with placebo; the between-treatment difference was 12.8 +/- 7.0 ng/liter (P = 0.039), representing a 38% increase with vildagliptin. In contrast, the mean glucagon DeltaAUC(0-60 min) during meal test with vildagliptin was 512 +/- 163 ng/liter x min vs. 861 +/- 130 ng/liter x min with placebo; the between-treatment difference was -349 +/- 158 ng/liter x min (P = 0.019), representing a 41% decrease with vildagliptin. CONCLUSIONS Vildagliptin enhances alpha-cell responsiveness to both the suppressive effects of hyperglycemia and the stimulatory effects of hypoglycemia. These effects likely contribute to the efficacy of vildagliptin to improve glycemic control as well as to its low hypoglycemic potential.

Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large Phase III type 2 diabetes population.

Aim: To assess the cardiovascular and cerebrovascular (CCV) safety of the dipeptidyl peptidase‐IV inhibitor vildagliptin.