Glucagon-like peptide-1 (GLP-1) receptor agonists (semaglutide [Wegovy, Ozempic, Rybelsus]) and dual incretin agonists (tirzepatide [Zepbound, Mounjaro])
Exenatide is an example of a glucagon-like peptide-1 (GLP-1) mimetic. These drugs increase insulin secretion and inhibit glucagon secretion. One of the major advances of GLP-1 mimetics is that they typically result in weight loss, in contrast to many medications such as insulin, sulfonylureas and thiazolidinediones. They are sometimes used in combination with insulin in T2DM to minimise weight gain.
Exenatide must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal.
Liraglutide is the other GLP-1 mimetic currently available. One the main advantages of liraglutide over exenatide is that it only needs to be given once a day.
Both exenatide and liraglutide may be combined with metformin and a sulfonylurea. Standard release exenatide is also licensed to be used with basal insulin alone or with metformin. Please see the BNF for a more complete list of licensed indications.
MOA
NICE state the following:
Consider adding exenatide to metformin and a sulfonylurea if: • BMI >= 35 kg/m² in people of European descent and there are problems associated with high weight, or • BMI < 35 kg/m² and insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities.
NICE like patients to have achieved a > 11 mmol/mol (1%) reduction in HbA1c and 3% weight loss after 6 months to justify the ongoing prescription of GLP-1 mimetics.
The major adverse effect of GLP-1 mimetics is nausea and vomiting. The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide, reporting that is has been linked to severe pancreatitis in some patients.
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