Glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...

-like peptide-1 receptor agonists, also known as GLP-1 receptor agonists (GLP-1-RA) or

incretin Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-gl ...

mimetics, are

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

s of the

GLP-1 receptor The glucagon-like peptide-1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised b ...

. This class of

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

s is used for the treatment of

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...

Some drugs are also approved for

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

. One of their advantages over older insulin secretagogues, such as

sulfonylurea Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the bet ...

s or

meglitinide Meglitinides or glinides are a class of drugs used to treat type 2 diabetes. Drugs Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997. Other drugs in this class include nateglinide (Starlix) and mitiglin ...

s, is that they have a lower risk of causing

hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

. GLP-1 has a short duration of action, so to overcome this limitation several modifications in either the drugs or the formulations are being developed. The 2022

ADA Ada may refer to: Places Africa * Ada Foah, a town in Ghana * Ada (Ghana parliament constituency) * Ada, Osun, a town in Nigeria Asia * Ada, Urmia, a village in West Azerbaijan Province, Iran * Ada, Karaman, a village in Karaman Province, ...

standards of medical care in diabetes include GLP-1-RA as a first line pharmacological therapy for type 2 diabetes, specifically in patients with

atherosclerotic cardiovascular disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

Health effects

A 2021 meta-analysis found a 12% reduction in all-cause mortality when GLP-1 analogs are used in the treatment of type 2 diabetes, as well as significant improvements in cardiovascular and renal outcomes. A ''

JAMA ''The Journal of the American Medical Association'' (''JAMA'') is a peer-reviewed medical journal published 48 times a year by the American Medical Association. It publishes original research, reviews, and editorials covering all aspects of biom ...

'' article

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

in 2018 (covering studies concerning GLP-1 agonists, DPP-4 inhibitors, and

SGLT2 inhibitor SGLT2 inhibitors, also called gliflozins or flozins, are a class of medications that modulate sodium-glucose transport proteins in the nephron (the functional units of the kidney), unlike SGLT1 inhibitors that perform a similar function in the ...

s) showed GLP-1 agonists were associated with lower

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

risk than controls. Preclinical research has suggested the possibility that the drugs may increase the risk of pancreatitis and pancreatic cancer. Analyses of human trials have not found an increased risk of pancreatitis but are insufficiently powered to rule out an effect on pancreatic cancer. Studies in rodents have shown GLP1 mediated thyroid c-cell hyperplasia. A 2020 Cochrane systematic review did not find enough evidence of reduction of all-cause mortality, serious adverse events, cardiovascular mortality, non-fatal

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

, non-fatal

, end-stage renal disease nor health-related quality of life when comparing

metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...

monotherapy to Glucagon-like peptide 1 analogues in the treatment of type 2 diabetes.

Approved

exenatide Exenatide, sold under the brand name Byetta and Bydureon among others, is a medication used to treat diabetes mellitus type 2. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after ...

(brand names Byetta and Bydureon, manufactured by

AstraZeneca AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includin ...

), approved in 2005/2012 *

liraglutide Liraglutide, sold under the brand name Victoza among others, is an anti-diabetic medication used to treat type 2 diabetes, obesity, and chronic weight management. In diabetes it is a less preferred agent compared to metformin. Its effects on l ...

(Victoza for diabetes, Saxenda for obesity, manufactured by

Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...

), approved in 2010 *

lixisenatide Lixisenatide (trade name Lyxumia in the European Union and Adlyxin in the U.S. and manufactured by Sanofi) is a once-daily injectable GLP-1 receptor agonist for the treatment of type 2 diabetes. Medical use Lixisenatide is used as adjunct to di ...

(Lyxumia in Europe, Adlyxin in the United States, manufactured by

Sanofi Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

), approved in 2016 *

albiglutide Albiglutide (trade names Eperzan in Europe and Tanzeum in the US) is a glucagon-like peptide-1 agonist (GLP-1 agonist) drug marketed by GlaxoSmithKline (GSK) for treatment of type 2 diabetes. As of 2017 it is unclear if it affects a person's risk ...

(Tanzeum, manufactured by GSK), approved in 2014 *

dulaglutide Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardiov ...

(Trulicity, manufactured by

Eli Lilly Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and r ...

), approved in 2014 *

semaglutide Semaglutide, sold under the brand names Ozempic, Wegovy and Rybelsus, is an antidiabetic medication used for the treatment of type 2 diabetes and as anti-obesity medication for long-term weight management, developed by Novo Nordisk in 2012. ...

(Ozempic and Rybelsus for diabetes, Wegovy for obesity, manufactured by Novo Nordisk), approved in 2017 *

tirzepatide Tirzepatide, sold under the brand name Mounjaro, is an antidiabetic medication used for the treatment of type 2 diabetes. Tirzepatide is given by weekly subcutaneous injection (under the skin). The most common side effects include nausea, vom ...

(Mounjaro, manufactured by Eli Lilly), approved in 2022

Under investigation

taspoglutide Taspoglutide is a former experimental drug, a glucagon-like peptide-1 agonist (GLP-1 agonist), that was under investigation for treatment of type 2 diabetes and being codeveloped by Ipsen and Roche. Initially, phase II trials reported it was e ...

, phase III halted Sept 2010 *efpeglenatide

Mechanism

These agents work by activating the GLP-1R, rather than inhibiting the breakdown of GLP-1 as do

DPP-4 inhibitors Inhibitors of dipeptidyl peptidase 4 (DPP-4 inhibitors or gliptins) are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4). They can be used to treat diabetes mellitus type 2. The first agent of the class – sita ...

, and are generally considered more potent.

References

{{Oral hypoglycemics and insulin analogs