Rationale for a titratable fixed-ratio co-formulation of a basal insulin analog and a glucagon-like peptide 1 receptor agonist in patients with type 2 diabetes

Abstract

Objective: Achieving and maintaining recommended glycemic targets, including those for glycated hemoglobin A1c (A1C), is key to improving outcomes in patients with type 2 diabetes (T2D). As fasting plasma glucose and postprandial glucose contribute to overall A1C, targeting both is essential for sustaining glycemic control.

Methods: This review examines the complementary mechanisms of action of glucagon-like peptide 1 (GLP-1) receptor agonists and basal insulin; they both enhance glucose-stimulated insulin release and suppress glucagon secretion. GLP-1 receptor agonists also slow gastric emptying and increase satiety.

Results: Adding a GLP-1 receptor agonist to therapy with a basal insulin analog has been associated with improved overall glycemic control, with comparable risk of hypoglycemia and no weight gain. Titratable fixed-ratio co-formulations of basal insulin and a GLP-1 receptor agonist have been shown to improve glycemic control, with less complex dosing schedules, possibly increasing treatment adherence. The slow titration of fixed-ratio co-formulations has been shown to reduce the occurrence and severity of gastrointestinal adverse events associated with the use of a separate GLP-1 receptor agonist. Titratable fixed-ratio co-formulations also mitigate insulin-associated weight gain, and show a comparable risk of hypoglycemia to basal insulin use alone.

Conclusions: The efficacy and safety of titratable fixed-ratio co-formulations have been demonstrated for insulin degludec/liraglutide and insulin glargine/lixisenatide in the DUAL and LixiLan trials, respectively, in both insulin-naive and -experienced patients. Titratable fixed-ratio co-formulations represent an attractive treatment option for many patients with T2D.

Keywords:

• Glucagon-like peptide 1
• Insulin degludec
• Insulin glargine
• Liraglutide
• Lixisenatide

Transparency

Declaration of funding

Writing/editorial support funded by Sanofi US, Inc.

Declaration of financial/other relationships

L.B. has disclosed he has received grants/research support from AstraZeneca, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Novo Nordisk, and Sanofi; is a Speaker for AstraZeneca, Janssen Pharmaceuticals, Inc., Merck & Co., Novo Nordisk, and Sanofi; and a Consultant for AstraZeneca, GlaxoSmithKline, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, and Sanofi. J.E.A. has disclosed that he is an Advisory Board member for Abbott Diabetes, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Sanofi; and a Speakers Bureau member for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, and Sanofi; he is a stock shareholder for NuSirt Biopharma. P.C. has disclosed that he has received a research and travel grant from Sanofi; is a Speaker for Janssen and Novo Nordisk; and a Consultant for Pfizer. J.A.D. has no relevant financial or other relationships to disclose. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors would like to thank Dr R. Aronson for his contributions and critical review of the manuscript. The authors received writing/editorial support in the preparation of this manuscript provided by Catarina Fernandes, PhD, and Keisha Peters, MSc, of Excerpta Medica, funded by Sanofi US, Inc.