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

Diabet. Med. 30, 179–188 (2013) Abstract 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 β‐cell destruction, particularly through preservation of β‐cell mass and prevention of apoptosis, and suppression of α‐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.