Mathematical modeling shows exenatide improved beta-cell function in patients with type 2 diabetes treated with metformin or metformin and a sulfonylurea
| Autor: | Loretta L. Nielsen, Andrea Mari, Ralph A. DeFronzo, Eleuterio Ferrannini, Nuwan Nanayakkara, Amy Halseth |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism Clinical Biochemistry Type 2 diabetes Pharmacology Placebo Biochemistry Placebos Endocrinology Double-Blind Method Insulin-Secreting Cells Internal medicine Diabetes mellitus medicine Humans Hypoglycemic Agents Glycemic Dose-Response Relationship Drug Venoms business.industry Biochemistry (medical) General Medicine Middle Aged Models Theoretical Postprandial Period medicine.disease Sulfonylurea Metformin Drug Combinations Sulfonylurea Compounds Postprandial Diabetes Mellitus Type 2 Exenatide Female Peptides business medicine.drug |
| Zdroj: | Hormone and metabolic research 38 (2006): 838–844. info:cnr-pdr/source/autori:Mari A., Nielsen L. L., Nanayakkara N., DeFronzo R. A., Ferrannini E., and Halseth A./titolo:Mathematical modeling shows exenatide improved beta-cell function in patients with type 2 diabetes treated with metformin or metformin and a sulfonylurea/doi:/rivista:Hormone and metabolic research/anno:2006/pagina_da:838/pagina_a:844/intervallo_pagine:838–844/volume:38 |
| Popis: | The incretin mimetic exenatide improved glycemic control and reduced body weight in patients with type 2 diabetes inadequately controlled with metformin+/-a sulfonylurea. We assessed postprandial beta-cell function by mathematical modeling, independent of confounding effects from differing ambient glucose levels among treatments. Subjects were 63% males, 55+/-10 years, BMI 33+/-6 kg/m2, HbA1C 8.1+/-1.1% (+/- SD) randomized to 5 microg exenatide or placebo twice daily for 4 weeks. Subsequently, one arm remained at 5 microg twice daily, one arm escalated to 10 microg twice daily, and one treatment arm remained on placebo for 26 weeks. Subjects continued metformin+/-a sulfonylurea. A subset with meal tests at baseline and week 30 were analyzed (n=73). Outcome measures were the model-based beta-cell function parameters dose-response relating insulin secretion to glucose concentration, rate sensitivity, and potentiation. Exenatide reduced postprandial glucose excursions. Modeling predicted an upward shift of the beta-cell dose-response. Model-predicted insulin secretion rate at a reference glucose concentration increased 72% (10 microg), increased 40% (5 microg), or decreased 21% (placebo) at week 30 [ p=0.015 (10 microg); p=0.045 (5 microg); vs. placebo]. At week 30, the 2-hour post-meal to basal potentiation factor ratio was increased to 1.53+/-0.10 (10 microg; p=0.0142 vs. placebo) or 1.40+/-0.08 (5 microg; p=0.0402 vs. placebo) compared with 1.15+/-0.06 (placebo). Exenatide caused an upward shift of the beta-cell dose-response and enhanced potentiation of insulin secretion. This model suggests exenatide improved beta-cell function in patients with type 2 diabetes treated with metformin+/-a sulfonylurea. |
| Databáze: | OpenAIRE |
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