Individualized, patient-centered use of lixisenatide for the treatment of type 2 diabetes mellitus

ABSTRACT

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with hyperglycemia, which can lead to serious vascular complications. Current treatment guidelines place particular emphasis on personalization of therapy. Within this guidance, the use of various second-line therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is recommended under certain circumstances.

Areas covered: Factors influencing glucose homeostasis, including gastric emptying and the associated cardiovascular (CV) risk when homeostasis is not maintained, are reviewed. Physiology relating to the mechanism of action of GLP-1 RAs is summarized, with a particular focus on lixisenatide. In addition, an overview of efficacy and safety data for lixisenatide is presented and the CV effects of GLP-1 RAs are examined. Finally, the rationale and clinical data supporting the combination of lixisenatide and basal insulin are explored.

Expert opinion: GLP-1 analogs meet a need for better glycemic control, with the added benefits of reduced hypoglycemic risk and body weight. The combination of a short-acting GLP-1 RA, such as lixisenatide, with a basal insulin, exploits the complementary effects of both of these therapies and seems well suited for the treatment of T2DM. However, further studies are needed to establish the associated CV risks and/or benefits of GLP-1 RAs.

KEYWORDS:

• Lixisenatide
• type 2 diabetes mellitus
• postprandial plasma glucose
• cardiovascular risk
• individualized treatment

Article highlights

• A major focus of the current T2DM treatment paradigm is the personalization of therapy to suit each individual’s needs.

• GLP-1 RAs are an appealing treatment option as they improve glycemic control and may also reduce body weight and hypoglycemic risk.

• Lixisenatide is a once-daily, short-acting GLP-1 RA that is associated with a delay in gastric emptying and, as a result, mediates particularly pronounced reductions in PPG [35-38].

• In T2DM, PPG is an independent risk factor of CV comorbidities; poor control of PPG is associated with a higher risk of myocardial infarction and all-cause mortality [67-70].

• It is crucial that PPG, and not only FPG, is adequately controlled to achieve target HbA_1c levels and potentially prevent CV risk.

• The use of a short-acting GLP-1 RA, such as lixisenatide, targeting predominantly PPG, in combination with a basal insulin, controlling mainly FPG, exploits the complementary effects of both of these therapies.

This box summarizes key points contained in the article.

Declaration of interest

M Hanefeld has served on advisory boards for Bristol-Myers Squibb, GlaxoSmithKline, Sanofi, and Takeda; and on speakers bureaus for Bayer HealthCare, Eli Lilly, GlaxoSmithKline, Roche Pharmaceuticals, Sanofi, and Takeda. D Raccah has served on an advisory panel and as an author for Bristol-Myers Squibb, Eli Lilly, Medtronic, Merck, Novartis, Novo Nordisk and Sanofi, and has served on an advisory panel and as speaker for AstraZeneca, Eli Lilly, Janssen, Novartis, Novo Nordisk and Sanofi. L Monnier has nothing to declare. 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.

Editorial assistance was utilized in the preparation of this manuscript, it was funded by Sanofi and carried out by Christina Holleywood, PhD, of Caudex (Oxford, UK).

Additional information

Funding

This review article was funded by Sanofi.