Peptide-based GLP-1/glucagon co-agonists: A double-edged sword to combat diabesity

Research output: Contribution to journalArticle

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Abstract

Diabesity is a new term for obesity-dependent diabetes, which is also associated with cardiovascular and other comorbidities with rising epidemic. Traditional treatments (sulfonylureas and thiazolidinediones) of diabetes are associated with weight gain, except metformin. Newer agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium glucose co-transporter 2 inhibitors (SGLT2i) are causing a modest weight reduction, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) are weight neutral. Oxyntomodulin, a native GLP-1/glucagon receptor agonist produced a superior weight loss and antihyperglycemic effects in obese mice and humans. Recent findings with synthetic dual GLP-1/glucagon receptor agonists have shown a good weight loss and antihyperglycemic profile in diet-induced obese (DIO) mice. Targeting combinations of GLP-1 receptor and glucagon receptor simultaneously with a single peptide may be the better strategy to achieve marked weight loss and considerable glycemic control in diabesity. Cardiovascular safety is very important with new antidiabetic agents due to rosiglitazone controversy. Current on-going clinical trials will clarify the cardiovascular effects of incretin-based therapies in near future. Based on current knowledge and rapid progress in the field, there is a strong possibility that the GLP-1/glucagon receptor co-agonists will likely be the new therapeutic treatment for diabesity for decades to come.

Original languageEnglish (US)
Pages (from-to)5-9
Number of pages5
JournalMedical Hypotheses
Volume95
DOIs
StatePublished - Oct 1 2016

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Glucagon Receptors
Glucagon-Like Peptide 1
Glucagon
Weight Loss
Peptides
Hypoglycemic Agents
Obese Mice
rosiglitazone
Sodium-Glucose Transporter 2
Oxyntomodulin
Dipeptidyl-Peptidase IV Inhibitors
Symporters
Incretins
Thiazolidinediones
Metformin
Weight Gain
Comorbidity
Obesity
Glucagon-Like Peptide-1 Receptor
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Peptide-based GLP-1/glucagon co-agonists : A double-edged sword to combat diabesity. / Soni, Hitesh.

In: Medical Hypotheses, Vol. 95, 01.10.2016, p. 5-9.

Research output: Contribution to journalArticle

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