Lixisenatide, a Once‐Daily Prandial Glucagon‐Like Peptide‐1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes

Abstract

Lixisenatide, a short-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), has been available in Europe since 2013 and was recently approved in the United States for the treatment of type 2 diabetes (T2D) as an adjunct to diet and exercise. The objective of this systematic review is to describe the pharmacology, pharmacokinetics, safety, and efficacy of lixisenatide in patients with T2D. We conducted a search of the EMBASE database, limited to human studies with abstracts available in English. Published conference abstracts, limited to the American Diabetes Association (ADA) and the European Association for the Study of Diabetes meetings in 2015, as well as abstracts presented at the ADA meeting in 2016, were also screened. The abstracts retrieved were assessed for relevance; review articles and meta-analyses focusing on GLP-1 RAs as a class were excluded. Lixisenatide induced mean reductions of 0.46-0.99% in glycated hemoglobin A (Hb ), 55.86-143.43 mg/dl in 2-hour postprandial glucose (PPG) levels, and 56.58-127.75 mg/dl in mealtime glucose level variations. Changes in fasting plasma glucose (FPG) levels and weight ranged from -21.98 to +5.41 mg/dl and from -2.96 to +0.3 kg, respectively, in patients with T2D enrolled in the GetGoal clinical program (a program of clinical trials that established the efficacy and safety profile of lixisenatide 20 μg once/day across patients with T2D with differing background therapies). Lixisenatide was well tolerated, demonstrating rates of symptomatic hypoglycemia of 0.8-42.9% and a very low rate of severe hypoglycemia (< 1.5%) as well as no increased risk of cardiovascular events. The most common adverse events were gastrointestinal in nature, mainly transient nausea and vomiting of mild-to-moderate severity. Lixisenatide effectively lowers Hb levels in patients with T2D through a mechanism of action complementary to that of agents that mainly target FPG, with the additional benefit of weight loss. Its once-daily administration schedule and effect on PPG levels make it an attractive option as add-on treatment to basal insulin therapy or oral antidiabetic agents.

Austrian Experience with Lixisenatide Under Real-Life Conditions: A Prospective Observational Study

“…Positive influences of lixisenatide on blood lipids and blood pressure were also in line with previous findings. Note that the observed mean weight loss of 4 kg in our real-life setting was stronger than in the GetGoal studies [ 11 ], possibly because of a higher BMI at baseline as well as analyses of patients who completed the treatment.…”

“…Only seven patients reported a discontinuation due to adverse events. Other reasons included the patients’ wishes [ 15 ], no reimbursement of the drug [ 11 ], and scheduled surgery [ 3 ].…”

“…Lixisenatide became commercially available in Austria in 2014, but ever since its use has been limited exclusively to centers of excellence, including restrictions to a certain subset of patients (e.g., with a body mass index (BMI) greater than 30 and preceding use of DPP-4 inhibitors). The drug has been extensively studied during the pivotal clinical GetGoal program, where its efficacy and safety in combination with oral antidiabetic drugs (OADs) and with basal insulin (BI) have been established [ 11 ]. In addition, the ELIXA outcome trial has confirmed the cardiovascular safety of the drug in a population of patients with recent acute coronary syndrome [ 12 ].…”

Comparison of lixisenatide in combination with basal insulin vs other insulin regimens for the treatment of patients with type 2 diabetes inadequately controlled by basal insulin: Systematic review, network meta‐analysis and cost‐effectiveness analysis

“…The recently released Standards of Medical Care in Diabetes 2018 by the American Diabetes Association (ADA) and Chinese T2DM guidelines by the China Diabetes Society (CDS) have largely reiterated these intensive insulin regimen recommendations, but have also proposed the option of adding a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) to BI. The activation of GLP‐1 receptors by a GLP‐1 RA enhances insulin secretion in a glucose‐dependent manner, inhibits glucagon release, delays gastric emptying and reduces appetite, with a beneficial effect on body weight and a low risk of hypoglycaemia …”

“…The activation of GLP-1 receptors by a GLP-1 RA enhances insulin secretion in a glucose-dependent manner, inhibits glucagon release, delays gastric emptying and reduces appetite, with a beneficial effect on body weight and a low risk of hypoglycaemia. [5][6][7] Lixisenatide is a selective, potent, once-daily GLP-1 RA that has been evaluated in a series of phase III clinical trials in T2DM patients (the GetGoal clinical trial programs). [8][9][10][11] It has been approved in the USA, the EU, Japan, and China for use with oral antidiabetic drugs (OADs) and/or BI in the treatment of patients with T2DM to achieve glycaemic control, when these agents, together with diet and exercise, do not provide adequate glycaemic control.…”