Lixisenatide: A New Daily GLP-1 Agonist for Type 2 Diabetes Management

McCarty, Delilah J.; Coleman, Megan; Boland, Cassie

doi:10.1177/1060028017689878

Cited by 22 publications

(15 citation statements)

References 25 publications

(174 reference statements)

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“…Lixisenatide (Lyxumia™/Adlyxin™, Sanofi/Zealand) is a second synthetic analogue of exendin‐4, which has been modified by extending the C terminus of native exendin‐4 to possess 6 lysine residues with deletion of one C‐terminal proline. The additional chemical modification slightly increased its half‐life to 3–4 h allowing for once‐daily subcutaneous administration, and, more importantly, it results in a four times more potent GLP‐1 receptor binding . Clinical efficacy of lixisenatide compared to exenatide BDI has been assessed in the 24‐week GetGoal‐X trial (Table ), a randomized open label actively controlled study in T2D patients that were inadequately controlled by metformin therapy .…”

Section: From Gila Monster Venom To Glp‐1 Analoguesmentioning

confidence: 99%

Peptide‐based multi‐agonists: a new paradigm in metabolic pharmacology

et al. 2018

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Obesity and its comorbidities, such as type 2 diabetes, are pressing worldwide health concerns. Available anti-obesity treatments include weight loss pharmacotherapies and bariatric surgery. Whilst surgical interventions typically result in significant and sustained weight loss, available pharmacotherapies are far less effective, typically decreasing body weight by no more than 5-10%. An emerging class of multi-agonist drugs may eventually bridge this gap. This new class of specially tailored drugs hybridizes the amino acid sequences of key metabolic hormones into one single entity with enhanced potency and sustained action. Successful examples of this strategy include multi-agonist drugs targeting the receptors for glucagon-like peptide-1 (GLP-1), glucagon and the glucose-dependent insulinotropic polypeptide (GIP). Due to the simultaneous activity at several metabolically relevant receptors, these multi-agonists offer improved body weight loss and glucose tolerance relative to their constituent monotherapies. Further advancing this concept, chimeras were generated that covalently link nuclear acting hormones such as oestrogen, thyroid hormone (T ) or dexamethasone to peptide hormones such as GLP-1 or glucagon. The benefit of this strategy is to restrict the nuclear hormone action exclusively to cells expressing the peptide hormone receptor, thereby maximizing combinatorial metabolic efficacy of both drug constituents in the target cells whilst preventing the nuclear hormone cargo from entering and acting on cells devoid of the peptide hormone receptor, in which the nuclear hormone might have unwanted effects. Many of these multi-agonists are in preclinical and clinical development and may represent new and effective tools in the fight against obesity and its comorbidities.

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Section: From Gila Monster Venom To Glp‐1 Analoguesmentioning

confidence: 99%

Peptide‐based multi‐agonists: a new paradigm in metabolic pharmacology

et al. 2018

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“…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 …”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Men

Qu²,

Luo³

et al. 2019

Diabetes Obesity Metabolism

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Aims To evaluate the comparative efficacy and safety of lixisenatide combined with basal insulin (BI) vs intensive premix insulin (premix), BI plus prandial insulin with the main meal (basal‐plus) or progressively covering all meals (basal‐bolus) in patients with type 2 diabetes mellitus (T2DM) inadequately controlled by BI, and the long‐term cost‐effectiveness of lixisenatide from a Chinese healthcare system perspective. Materials and methods Randomized controlled trials (RCTs) published between 1998 and 2018 were systematically searched. The clinical efficacy and safety of each treatment were compared by network meta‐analysis (NMA). The IQVIA CORE Diabetes Model was used to estimate the lifetime quality‐adjusted life‐years (QALYs) and direct medical costs of patients treated with different strategies. Results Eight RCTs were finally included. Lixisenatide plus BI showed a similar reduction in HbA1c from baseline compared with premix, basal‐plus and basal‐bolus. There were significant differences in the change of body weight in favour of lixisenatide plus BI compared with the three insulin regimens. The risk of symptomatic hypoglycaemia of lixisenatide plus BI was significantly lower compared with premix and basal‐bolus. Lixisenatide plus BI was cost‐effective compared with premix, basal‐plus and basal‐bolus with incremental cost‐effectiveness ratios of Chinese yuan (CNY) 87 219, 48 173 and 48 670 per QALY gained, respectively, under the threshold of three times the gross domestic product (GDP) per capita in China. Conclusions Lixisenatide plus BI shows a similar HbA1c reduction compared with insulin regimens, accompanied by lower risk of hypoglycaemia and greater body weight reduction. It is a cost‐effective treatment alternative for patients with T2DM inadequately controlled by BI in China.

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“…8 The absorption of Acetaminophen was delayed by the concomitant administration of Exenatide, 9 Liraglutide 10 or Lixisenatide. 11 The interaction between Acetaminophen and GLP-1 agonists is minimal and clinically insignificant and no management required. Delayed absorption of Acetaminophen could be avoided by 1 hour prior to the GLP-1 agonists' administration.…”

Section: Acetaminophen (Paracetamol)mentioning

confidence: 99%

Pharmacologically relevant drug interactions of Glucagon-like peptide-1 receptor agonists

Maideen¹

2019

JAPLR

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Glucagon-like peptide-1 receptor agonists are incretin mimetics and they help to manage the blood glucose of patients with type 2 diabetes mellitus. The gastric emptying is delayed by the administration of Glucagon-like peptide-1 receptor agonists and hence the absorption of orally administered medications such as Acetaminophen, Digoxin, Warfarin, Oral contraceptive pills, Metformin, Statins, Angiotensin Converting Enzyme Inhibitors and Griseofulvin delayed by their concomitant use. It has been observed that the pharmacokinetics of all these drugs did not get altered by the concurrent administration of Glucagon-like peptide-1 receptor agonists. Moreover, the delay in absorption of interacting drugs could be avoided by taking 1 hour before the administration of Glucagon-like peptide-1 receptor agonists.

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Lixisenatide: A New Daily GLP-1 Agonist for Type 2 Diabetes Management

Abstract: Lixisenatide provides an additional GLP-1RA option, which may have more postprandial blood glucose-lowering effects than the other agents in the class because of its shorter half-life and effects on delaying gastric emptying.

Cited by 22 publications

References 25 publications

Peptide‐based multi‐agonists: a new paradigm in metabolic pharmacology

Peptide‐based multi‐agonists: a new paradigm in metabolic pharmacology

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

Pharmacologically relevant drug interactions of Glucagon-like peptide-1 receptor agonists

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