GLP-1R agonist therapy for diabetes: benefits and potential risks

@article{Samson2013GLP1RAT,
  title={GLP-1R agonist therapy for diabetes: benefits and potential risks},
  author={Susan L. Samson and Alan J. Garber},
  journal={Current Opinion in Endocrinology \& Diabetes and Obesity},
  year={2013},
  volume={20},
  pages={87–97}
}
  • S. Samson, A. Garber
  • Published 1 April 2013
  • Medicine, Biology
  • Current Opinion in Endocrinology & Diabetes and Obesity
Purpose of review Glucagon-like peptide 1 receptor (GLP-1R) agonists provide good glycemic control combined with low hypoglycemia risk and weight loss. Here, we summarize the recently published data for this therapy class, focusing on sustainability of action, use in combination with basal insulin, and the efficacy of longer acting agents currently in development. The safety profile of GLP-1R agonists is also examined. Recent findings GLP-1R agonists provide sustained efficacy and their… 
GLP-1 Receptor Agonists
TLDR
Glucagon-like peptide-1 receptor agonists are a class of injectable glucose-lowering agents that lower A1C with added benefits of weight loss and improved cardiovascular risk markers and target multiple pathophysiologic mechanisms in patients with T2D and improve glycemic control.
Insulin dose adjustments with add-on glucagon-like peptide-1 receptor (GLP-1R) agonists in clinical practice
TLDR
Based on currently reported evidence, a reduction of basal insulin and a decrease of prandial insulin by 30 – 40% is recommended on addition of GLP-1RAs, and an overview of the current knowledge in this rapidly changing field is provided.
Differential effects of prandial and non-prandial GLP-1 receptor agonists in type 2 diabetes therapy
TLDR
Prandial GLP-1 RAs have a short plasma half-life and are particularly effective at targeting PPG elevations, whereas long-acting non-prandial glucagon-like peptide-1 receptor agonists are more effective at reducing fasting plasma glucose, highlighting the potential for treatment with these agents to be tailored to the need of individual patients and their glycemic imbalance.
Effects of glucagon-like peptide-1 receptor agonists on renal function.
TLDR
Based on the current evidence, exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease, and liraglutide is not eliminated by kidneys or hepatic mechanisms, but it should be used with caution.
GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects
TLDR
The therapeutic effects and possible mechanisms of action of GLP-1RAs in the nervous, cardiovascular, and endocrine systems and their correlation with metabolism, tumours and other diseases are reviewed.
An Updated Review on Cancer Risk Associated with Incretin Mimetics and Enhancers
TLDR
Based on current evidence, continuous monitoring of the cancer issues related to incretin-based therapies is required, even though the benefits may outweigh the potential cancer risk in the general patients with type 2 diabetes mellitus.
Liraglutide Versus Lixisenatide: Long-Term Cost-Effectiveness of GLP-1 Receptor Agonist Therapy for the Treatment of Type 2 Diabetes in Spain
TLDR
Long-term projections in the Spanish setting suggest that liraglutide 1.8 mg is likely to be cost-effective compared with lixisenatide 20 μg in type 2 diabetes patients who have not achieved glycemic control targets on metformin monotherapy.
Safety and efficacy of a glucagon-like peptide-1 receptor agonist added to basal insulin therapy versus basal insulin with or without a rapid-acting insulin in patients with type 2 diabetes: results of a meta-analysis
TLDR
Addition of GLP-1 RA to basal insulin provided improved glycemic control, led to weight reduction and similar hypoglycemia rates versus an intensified insulin strategy; however, symptomatic hypoglycesmia rates were significantly lower when compared with a basal insulin plus RAI.
Dulaglutide: a novel once-weekly glucagon-like peptide-1 receptor agonist
TLDR
Clinical Phase II and III trials show dose-dependent reductions of HbA1c up to 1.6%, reduction in fasting plasma glucose up to 2.7 mmol/l and weight reductions up to 3.2 kg.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 79 REFERENCES
GLP-1 Receptor Agonists
TLDR
Glucagon-like peptide-1 receptor agonists are a class of injectable glucose-lowering agents that lower A1C with added benefits of weight loss and improved cardiovascular risk markers and target multiple pathophysiologic mechanisms in patients with T2D and improve glycemic control.
A comparison of currently available GLP-1 receptor agonists for the treatment of type 2 diabetes
  • E. Montanya
  • Medicine
    Expert opinion on pharmacotherapy
  • 2012
TLDR
Liraglutide seems to be the most effective GLP-1 receptor agonist in terms of HbA1c reduction and weight loss, and exenatide ER generally outperforms exen atide BID and is a good option for patients who struggle to adhere to more frequent regimens.
Combining GLP‐1 receptor agonists with insulin: therapeutic rationales and clinical findings
TLDR
Data from clinical studies support the therapeutic potential of GLP‐1RA–insulin combination therapy, typically showing beneficial effects on glycaemic control and body weight, with a low incidence of hypoglycaemia and, in established insulin therapy, facilitating reductions in insulin dose.
GLP-1 receptor agonists today.
Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications.
  • M. Nauck
  • Medicine, Biology
    The American journal of medicine
  • 2011
Cardiovascular Benefits of GLP-1-BasedTherapies in Patients with Diabetes Mellitus Type 2: Effects on Endothelial and Vascular Dysfunction beyond Glycemic Control
TLDR
The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLp-1 receptor agonists or DPP-IV inhibitors.
Lixisenatide, a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus.
TLDR
The results of phase III trials are awaited for confirmation of the anticipated effects of lix Eisenatide on glycemic measures and weight; favorable results would place lixisenatide for consideration among other GLP-1R agonists in the treatment armamentarium for T2DM.
Patient‐reported outcomes in trials of incretin‐based therapies in patients with type 2 diabetes mellitus
TLDR
People with T2DM were highly satisfied with modern incretin‐based therapies compared with traditional therapies, and it is plausible that superior patient‐reported benefits found in clinical trials may translate into improved, clinically meaningful, long‐term outcomes through increased treatment acceptability.
Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease.
TLDR
It is concluded that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease and adds yet another salutary property of the peptide useful in diabetes treatment.
...
1
2
3
4
5
...