| Title |
Do current incretin mimetics exploit the full therapeutic potential inherent in GLP-1 receptor stimulation?
|
|---|---|
| Published in |
Diabetologia, June 2013
|
| DOI | 10.1007/s00125-013-2953-6 |
| Pubmed ID | |
| Authors |
M. A. Nauck, O. Baranov, R. A. Ritzel, J. J. Meier |
| Abstract |
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are incretin-derived glucose-lowering agents that have been used for the treatment of type 2 diabetes since 2007. Agents such as exenatide (short-acting and once weekly preparations), liraglutide, taspoglutide, albiglutide and lixisenatide lower fasting glucose and HbA1c upon subcutaneous injection, leading to glycaemic control that is equivalent to, or better than, that observed with other oral glucose-lowering agents or bedtime insulin. However, varying proportions of patients report nausea and vomiting, adverse events that typically narrow the therapeutic dose range. Furthermore, GLP-1 RAs reduce fasting glucose to a clinically meaningful extent, but not into the normal range. In contrast, where GLP-1 is administered as a short-term intravenous infusion, a full normalisation of glucose concentrations (approximately 5 mmol/l) has been observed without any risk of gastrointestinal side effects. Subcutaneous infusions or injections of GLP-1 are much less effective. The present analysis relates the proportion of patients who report nausea following treatment with GLP-1 and GLP-1 RAs to the clinical effectiveness of the treatment (represented by the fasting glucose concentration achieved with treatment). The results suggest that GLP-1 RAs injected into the subcutaneous compartment do not exploit the full potential inherent in GLP-1 receptor activation. Reasons for this may include modifications of the peptide molecules in the subcutaneous environment or high local concentrations triggering side effects through GLP-1 receptors on autonomic nerves in subcutaneous adipose tissue. Elucidation of the mechanisms underlying differential responses to GLP-1/GLP-1 RAs administered intravenously vs subcutaneously may help to develop improved agents or modes of administration that are more effective and have fewer side effects. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 50% |
| Germany | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 2% |
| Unknown | 44 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 13% |
| Other | 5 | 11% |
| Student > Ph. D. Student | 5 | 11% |
| Student > Bachelor | 4 | 9% |
| Professor | 3 | 7% |
| Other | 7 | 16% |
| Unknown | 15 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 20 | 44% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 7% |
| Agricultural and Biological Sciences | 3 | 7% |
| Neuroscience | 2 | 4% |
| Computer Science | 1 | 2% |
| Other | 1 | 2% |
| Unknown | 15 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 August 2013.
All research outputs
#15,276,424
of 22,716,996 outputs
Outputs from Diabetologia
#4,445
of 5,030 outputs
Outputs of similar age
#122,084
of 197,455 outputs
Outputs of similar age from Diabetologia
#36
of 51 outputs
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