Potential role of non-insulin adjunct therapy in Type 1 diabetes

TY - JOUR

T1 - Potential role of non-insulin adjunct therapy in Type 1 diabetes

AU - George, P.

AU - McCrimmon, R J

N1 - Copyright 2013 Elsevier B.V., All rights reserved.

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Despite improvements in the pharmacodynamics of injectable insulin and better insulin delivery systems, glucose control remains suboptimal in the majority of individuals with Type 1 diabetes. Profound defects in the physiological processes that normally maintain glucose homeostasis contribute to the difficulty in achieving glycaemic targets. Non-insulin-based adjunct treatments offer a potential means of complementing intensive insulin therapy in Type 1 diabetes through addressing some of the physiological disturbances that result from endogenous ß-cell destruction, particularly through preservation of ß-cell mass and prevention of apoptosis, and suppression of a-cell glucagon release in the postprandial state. The former approach applies most readily to newly diagnosed C-peptide-positive Type 1 diabetes, while the latter to established C-peptide-negative Type 1 diabetes. This review focuses primarily on the clinical trial data available on the use of non-insulin-based therapies in longer-duration Type 1 diabetes. We conclude that metformin may prove useful in macrovascular disease reduction, while pramlintide, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors and leptin co-therapies may reduce HbA(1c) , glucose variability, postprandial glucose excursions and body weight. These early studies are encouraging and offer novel and potentially very effective approaches to the treatment of Type 1 diabetes, but the evidence is largely restricted to small, often uncontrolled trials. As such, these therapies cannot be currently recommended for routine clinical practice. There is a clear need to support large, multi-centre randomized controlled trials designed to establish whether adjunct insulin therapy has a place in the modern management of Type 1 diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

AB - Despite improvements in the pharmacodynamics of injectable insulin and better insulin delivery systems, glucose control remains suboptimal in the majority of individuals with Type 1 diabetes. Profound defects in the physiological processes that normally maintain glucose homeostasis contribute to the difficulty in achieving glycaemic targets. Non-insulin-based adjunct treatments offer a potential means of complementing intensive insulin therapy in Type 1 diabetes through addressing some of the physiological disturbances that result from endogenous ß-cell destruction, particularly through preservation of ß-cell mass and prevention of apoptosis, and suppression of a-cell glucagon release in the postprandial state. The former approach applies most readily to newly diagnosed C-peptide-positive Type 1 diabetes, while the latter to established C-peptide-negative Type 1 diabetes. This review focuses primarily on the clinical trial data available on the use of non-insulin-based therapies in longer-duration Type 1 diabetes. We conclude that metformin may prove useful in macrovascular disease reduction, while pramlintide, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors and leptin co-therapies may reduce HbA(1c) , glucose variability, postprandial glucose excursions and body weight. These early studies are encouraging and offer novel and potentially very effective approaches to the treatment of Type 1 diabetes, but the evidence is largely restricted to small, often uncontrolled trials. As such, these therapies cannot be currently recommended for routine clinical practice. There is a clear need to support large, multi-centre randomized controlled trials designed to establish whether adjunct insulin therapy has a place in the modern management of Type 1 diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

UR - https://www.scopus.com/pages/publications/84872714268

U2 - 10.1111/j.1464-5491.2012.03744.x

DO - 10.1111/j.1464-5491.2012.03744.x

M3 - Article

C2 - 22804102

SN - 1464-5491

VL - 30

SP - 179

EP - 188

JO - Diabetic Medicine

JF - Diabetic Medicine

IS - 2

ER -