Non‐insulin treatments for Type 1 diabetes: critical appraisal of the available evidence and insight into future directions

• Published in: Diabetic medicine Vol. 36; no. 6; pp. 665 - 678
• Main Authors: Wright, L. A., Hirsch, I. B.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-06-2019
• Subjects: Acidosis; Body weight loss; Cardiovascular diseases; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 1 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Endocrinology - methods; Endocrinology - trends; Glucagon; Glucose; Glucose transporter; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents - classification; Hypoglycemic Agents - therapeutic use; Insulin; Limiting factors; Metformin; Metformin - therapeutic use; Sodium; Therapies, Investigational - methods; Therapies, Investigational - trends; Thiazolidinediones - therapeutic use
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/dme.13941

Intensive insulin therapy is the mainstay of treatment for people with Type 1 diabetes, but hypoglycaemia and weight gain are often limiting factors in achieving glycaemic targets and decreasing the risk of diabetes‐related complications. The inclusion of pharmacological agents used traditionally in Type 2 diabetes as adjuncts to insulin therapy in Type 1 diabetes has been explored, with the goal of mitigating such drawbacks. Pramlintide and metformin result in modest HbA1c and weight reductions, but their use is limited by poor tolerability and, in the case of pramlintide, by frequency of injections and cost. The addition of glucagon‐like peptide‐1 receptor agonists to insulin results in improved glycaemic control, reduced insulin doses and weight loss, but this is at the expense of higher rates of hypoglycaemia and hyperglycaemia with ketosis. Sodium‐glucose co‐transporter‐2 and dual sodium‐glucose co‐transporter‐2 and ‐1 inhibitors also improve glucose control, but with reductions in weight and insulin requirements potentiating the risk of acidosis‐related events and hypoglycaemia. The high proportion of people with Type 1 diabetes not achieving glycaemic targets, the negative clinical impact of intensive insulin therapy and the rise in obesity and cardiovascular disease and mortality, underline the need for individualized clinical care. The evaluation of new therapies, effective in Type 2 diabetes, as adjuncts to insulin therapy represents a promising strategy, particularly given the beneficial effects on cardiovascular and renal outcomes in people with Type 2 diabetes with or at high risk of complications that are also observed in patients with Type 1 diabetes. As the population with Type 1 diabetes ages, our mission is to evolve and provide better tools and improved therapies to excel, not only in glycaemic control but also in risk reduction and reduction of complications.
What's new?
Multiple therapeutic options have been developed and approved for the treatment of Type 2 diabetes, and are used as adjunctive therapies to insulin in Type 1 diabetes. We review the current evidence on such therapies and evaluate their utility as a strategy to reduce the drawbacks of intensive insulin therapy and potentially reduce complications in Type 1 diabetes.
Individualization of the care of people with diabetes is now emphasized more than ever, with adjunctive therapies now available to address previous unmet needs. Clinicians are able to weigh the advantages and hypothetical long‐term benefits of such treatments against the known elevated risks of acute complications and uncertain long‐term effects.