Non-insulin pharmacological therapies for treating type 1 diabetes

ABSTRACT

Introduction: Despite intensified insulin treatment, many persons with type 1 diabetes (T1D) do not achieve glycemic and metabolic targets. Consequently, non-insulin chemical therapies that improve glycemic control and metabolic parameters without increasing the risk of adverse events (including hypoglycemia) are of interest as adjunct therapies to insulin.

Areas covered: In this review, the authors discuss the efficacy and safety of non-insulin therapies, including pramlintide, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP-4), sodium-glucose cotransporter (SGLT1 and SGLT2) inhibitors, metformin, sulfonylureas, and thiazolidinediones as add-on therapies to insulin in T1D.

Expert opinion: The current evidence shows that the efficacy of non-insulin therapies as add-on therapies to insulin is minimal or modest with an average HbA1c reduction of 0.2–0.5% (2–6 mmol/mol). Indeed, the current focus is on the development of SGLT inhibitors as adjuncts to insulin in type 1 diabetes. Studies of subgroups with obesity, residual beta-cell function (including newly diagnosed patients) and patients prone to hypoglycemia could be areas of future research.

KEYWORDS:

• Type 1 diabetes
• T1DM
• T1D
• pramlintide
• amylin
• glucagon-like peptide-1
• GLP-1RA
• dipeptidyl peptidase-4 inhibitor
• DPP-4
• sodium-glucose cotransporters
• SGLT-1
• SGLT-2
• metformin
• sulfonylurea
• SU
• thiazolidinediones
• TZD

Article highlights

• Many persons with type 1 diabetes do not achieve glycemic and metabolic targets.

• To achieve these treatment targets, combination therapy using agents with complementary actions to insulin may be appropriate.

• The efficacy of non-insulin therapies as add-on to insulin is minimal or modest with an average HbA1c reduction of 0.2–0.5% (2–6 mmol/mol).

• The current non-insulin pharmaceutical agents do not hold promise for achieving improved glycemic control with reduced insulin requirements and a lower risk of hypoglycemic events without increasing the frequency of adverse events.

• GLP-1RAs and SGLT inhibitors show most promise regarding future therapies

• Future research should focus on patients with obesity, residual beta-cell function (including newly diagnosed patients) and patients prone to hypoglycemia.

This box summarizes key points contained in the article.

Declaration of Interest

CS Frandsen has consulted with Novo Nordisk received an unrestricted research grant from them as well. TF Dejgaard has consulted with Novo Nordisk and received an unrestricted research grant from Novo Nordisk and AstraZeneca. JJ Holst has consulted for Novo Nordisk and Merck Sharp and Dohme. S Madsbad has served as a consultant or adviser or received fees for speaking from Novartis, Novo Nordisk, Merck Sharp and Dohme, Pfizer Inc, Abbott Laboratories, Sanofi, AstraZeneca, Johnson & Johnson, Roche, Mankind, Bristol-Myers Squibb, Antarcia, Boehringer Ingelheim, Eli Lilly and Company, Amgen Inc, Schering-Plough and Tageta. 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.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.