Moving beyond subcutaneous insulin: the application of adjunctive therapies to the treatment of type 1 diabetes

ABSTRACT

Introduction: With the discovery of insulin nearly a century ago, the diagnosis of Type 1 Diabetes (T1D) transformed from a death sentence to a chronic medical condition. Despite the advances that have been made, the vast majority of those living with T1D still struggle to achieve targeted control. Yet, a plethora of agents have been developed to treat those with Type 2 Diabetes. Exploration of how these agents may benefit those with T1D has been an area of intense investigation, especially due to the overweight/obesity epidemic, which now afflicts more than 60% of those living with T1D.

Areas covered: This review focuses on agents that have been utilized, including inhaled insulin preparations, pramlintide, metformin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dual SGLT1/2 inhibitors. Furthermore, with approval of the first hybrid closed loop (CL) system, the development of dual hormone CL systems is being explored. While the most common agent applied to these dual systems has been glucagon, research has been conducted to assess how some of the adjunctive therapies described above could aide with achieving postprandial glucose control while on CL insulin delivery.

Expert opinion: By becoming less insulin-centric and incorporating some of these other agents, it is possible we may be able to better combat T1D.

KEYWORDS:

• Type 1 diabetes
• adjunctive therapy
• glycemic control
• insulin

Article highlights

• The vast majority of those living with T1D do not achieve targeted glycemic control recommended by the American Diabetes Association.

• T1D represents a condition that is not only defined by insulin deficiency. Dysregulated glucagon secretion following meals occurs early in the disease course, and may lead to the need for higher insulin doses to prevent postprandial hyperglycemia.

• Many agents approved for use in T2D hold the potential to aid with glycemic control in those with T1D. These include inhaled insulin, pramlintide, metformin, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors, and dual SGLT1/2 inhibitors. Pramlintide is the only currently approved adjunctive therapy, but assessment of the other agents is ongoing in those with T1D.

• The CL insulin delivery systems offer the potential to attain targeted glycemic control in the overnight period; however, due to difficulty in achieving targeted control in the post-prandial period, a hybrid approach with administration of pre-meal boluses for carbohydrate consumption remains common.

• Dual hormone CL systems are in development. While glucagon has been the most commonly studied agent, application of other adjunctive therapies has been assessed in pilot and feasibility studies.

This box summarizes key points contained in the article.

Declaration of interest

J Sherr is on the medical advisory board for Bigfoot Biomedical and Insulet Corporation. She is also a Consultant for Medtronic Diabetes. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This manuscript was funded by Juvenile Diabetes Research Foundation (5-ECR-2014-112-A-N); National Institutes of Health; National Center for Advancing Translational Sciences; Stephen I. Morse Fund; YALE Clinical and Translational Science Award (UL1TR000142).