Vildagliptin Added to Metformin on β-Cell Function After a Euglycemic Hyperinsulinemic and Hyperglycemic Clamp in Type 2 Diabetes Patients

Derosa, Giuseppe; Ragonesi, Pietro D.; Carbone, Anna; Fogari, Elena; Bianchi, Lucio; Bonaventura, Aldo; Romano, Davide; Cicero, Arrigo F G; Maffioli, Pamela

doi:10.1089/dia.2011.0278

Cited by 47 publications

(35 citation statements)

References 44 publications

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“…However, eight trials reported co-primary outcomes to HbA 1c change from baseline [54, 59, 62, 64, 82–85], such as change from baseline in FPG, 2-hour postprandial glucose, BMI, body weight, fasting lipids, fasting plasma insulin, fasting insulin, fasting C-peptide, vital signs, and number/proportion of patients with adverse events, homeostatic model assessment-insulin resistance (β-cell function), and proportion of patients achieving HbA 1c <7%. In five trials, HbA 1c change from baseline was not the primary outcome [36, 53, 68, 86, 87].…”

Section: Resultsmentioning

confidence: 99%

Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison

Craddy

Palin²,

Johnson³

2014

Diabetes Ther

111

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ObjectiveTo compare the safety and efficacy of the dipeptidylpeptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes and inadequate glycemic control.DesignSystematic review of randomized controlled trials (RCTs), health economic evaluation studies, systematic reviews, and meta-analyses, followed by primary Bayesian mixed treatment comparison meta-analyses (MTCs), and secondary frequentist direct-comparison meta-analyses using a random-effects model. Outcomes were reported as weighted mean change from baseline, or odds ratio (OR) with 95% credible interval.Data sourcesMEDLINE, MEDLINE In-Process, EMBASE, and BIOSIS via Dialog ProQuest; Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews via EBSCO; four diabetes and two technical congress abstracts; and health technology assessment organization websites.Eligibility criteriaPatients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment.Data extraction and analysisTitle/abstracts were reviewed for eligibility, followed by full-text review of publications remaining after first pass. A three-person team filtered articles and an independent reviewer checked a random selection (10%) of filtered articles. Data extraction and quality assessment of studies were also independently reviewed. Five DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin) were compared via meta-analysis (where data were available) as monotherapy, dual therapy (plus metformin, sulfonylurea, pioglitazone, or insulin), and triple therapy (plus metformin/sulfonylurea).ResultsThe review identified 6,601 articles; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis. MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin (HbA1c) or body weight, or the proportions of patients achieving HbA1c <7% or experiencing a hypoglycemic event, apart from in patients on alogliptin plus metformin, who achieved HbA1c <7% more frequently than those treated with saxagliptin plus metformin [OR 6.41 (95% CI 3.15–11.98) versus 2.17 (95% CI 1.56–2.95)].ConclusionsThis systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes, either as monotherapy or combination therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0061-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison

Craddy

Palin²,

Johnson³

2014

Diabetes Ther

111

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“…We have already conducted several studies on incretins, two studies on exenatide [14,15], three studies on DPP-4 inhibitors sitagliptin and vildagliptin [16][17][18], a review about saxagliptin effects in combination with metformin [19], and a review about DPP-4 inhibitors [20] proving that, once metformin fails to maintain glycemic control, DPP-4 inhibitors addition could be a valid option to lower HbA 1c levels and to improve β-cell function without increasing body weight, also preventing the risk of hypoglycemia posed by sulfonylureas. Given the increasing use of incretins and the recent release of a new formulation of exenatide to be administered once weekly, this time we decided to conduct a review analyzing the clinical efficacy and safety of GLP-1 receptor agonists exenatide and liraglutide, both alone and in combination with other anti-diabetic drugs, including the most important studies involving them in the latest ten years.…”

Section: Incretins Physiological Aspectsmentioning

confidence: 99%

GLP-1 Agonists Exenatide and Liraglutide: A Review About Their Safety and Efficacy

Derosa

Maffioli²

2012

CCP

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Recently incretin-based therapies have been developed in the clinical practice, this class includes both the dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin), and the glucagon-like peptide- 1 (GLP-1) receptor agonists [exenatide, exenatide long acting release (LAR) and liraglutide]. In particular exenatide and liraglutide have structural similarity and bind to the GLP-1 receptor, displaying a similar broad range of activities relevant to improving glycemic control, including stimulation of insulin secretion and reduction of glucagon secretion, both in a glucose-dependent manner. Furthermore, GLP-1 slows gastrointestinal motility and increases satiety, reducing the food intake; it also promotes β-cell proliferation and probably neogenesis, while reducing apoptosis in animal models. We conducted a review analyzing clinical efficacy and safety of GLP-1 receptor agonists exenatide and liraglutide, both alone and in combination with other anti-diabetic drugs, including the most important studies about them in the latest ten years. We concluded that GLP-1 receptor agonists appear to be a good choice to decrease HbA1c levels and to lower postprandial blood glucose levels. They also suppress glucagon secretion and slow gastric motility. They also have positive effects on β-cell function and they gave a significant decrease of body weight. They are not associated with hypoglycemia, but cause a relatively high frequency of gastrointestinal disturbances, with some patients experiencing one or more episodes of nausea, vomiting, or diarrhea. However, after an evaluation of the advantages and the disadvantages, we concluded that, once metformin fails to reach an adequate glycemic control, GLP-1 receptor agonists can be a valid alternative, especially in obese type 2 diabetic patients. GLP-1 receptor agonists should be considered also in patients in therapy with metformin and another agent, such as a sulfonylurea, because of the minor risk of developing hypoglycemia and the positive effect on body weight.

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“…The arginine stimulation test (AST) has been used in islet autotransplantation studies in which the insulin secretory response to arginine correlates with the number of transplanted islets in this patient population (17,18). Although these various tests have been used to detect and quantify phenotypic differences across health and disease, their application to evaluate pharmacologic interventions has been demonstrated in a limited number of studies (19–21). In particular, there is scant information on their variability and reproducibility characteristics.…”

Section: Introductionmentioning

confidence: 99%

Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of β-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series

Shankar

Vella

Raymond³

et al. 2016

Diabetes Care

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OBJECTIVEStandardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states.RESEARCH DESIGN AND METHODSParticipants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT).RESULTSFrom the MMTT, insulin secretion in T2DM was >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations.CONCLUSIONSStandardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use.

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Vildagliptin Added to Metformin on β-Cell Function After a Euglycemic Hyperinsulinemic and Hyperglycemic Clamp in Type 2 Diabetes Patients

Abstract: The addition of vildagliptin to metformin gave a better improvement of glycemic control, insulin resistance, and β-cell function compared with metformin alone.

Cited by 47 publications

References 44 publications

Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison

Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison

GLP-1 Agonists Exenatide and Liraglutide: A Review About Their Safety and Efficacy

Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of β-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series

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