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GLP-1 agonists (type 2)

GLP-1 (glucagon-like peptide 1) receptor agonists

DM is a progressive disease caused by insulin resistance and a partial or complete lack of insulin produced by the pancreas’ beta cells. Frequently, T2DM is not diagnosed until the beta cell have been damaged enough to impair their function (decreased insulin secretion). This is made worse by insulin resistance. The harder the beta cells work to compensate for insulin resistance and hyperglycemia, the quicker the disease progression. Anti-hyperglycemic agents are used to help the person achieve glycemic goals (HbA1c<7.0%). Metformin (see previous post) has been deemed the first line treatment for this, however there are many other agents that can work in conjunction with metformin to achieve optimal glucose control (and therefore preserve beta cell function) in T2DM. GLP-1 receptor agonists are incretin-based therapies that have been known to decrease blood glucose levels significantly without hypoglycemia AND increased weight loss (woohoo)! Recently, they have even been recommended in place of rapid acting insulin to intensify basal insulin treatment in T2DM. Here is how they work…

Glucagon-like peptide-1 (GLP-1) is produced by special cells in the digestive tract which helps to lower blood glucose levels by enhancing the production of insulin and decreasing the production of glucagon; both, in a glucose-dependent fashion. GLP-1 also helps to replenish insulin stores in the beta cells preventing their exhaustion during insulin secretion and therefore preserving their function. Very importantly, GLP-1 reduces post-meal hyperglycemia by slowing gastric emptying therefore decreasing appetite and increasing weight loss!

Additionally, some GLP-1 receptor agonists have been associated with a decreased risk of cardiovascular mortality, non-fatal heart attacks, and non-fatal strokes. The number one cause of mortality in T2DM is cardiovascular disease, so this is a BIG plus! Injectable GLP-1 receptor agonists are active synthetic analogs that offer the same benefits of endogenous (native) GLP-1 but are less resistant to degradation.

All GLP-1 receptor agonists are injectable. Some are twice daily; exenatide (Byetta). Some are once daily; lixisenatide and liraglutide (Victoza and Saxenda). And some are once weekly; albiglutide (Tanzeum-now off the market), exenatide (Bydureon), semaglutide (Ozempic) and dulaglitide (Trulicity). Imagine controlling your glucose levels with a once weekly injection!

Now let’s talk about some possible adverse effects…

The most common side effects of GLP-1 receptor agonists are injection site reactions, nausea, and diarrhea (because of the slowed gastric emptying). This usually resolves after a few weeks.  Many clinicians will start the drug at a low dose (and titrate up) to help decrease or prevent these side effects. When used in conjunction with insulin or a sulfonylurea, your clinician may decrease your dosage to decrease your risk of hypoglycemia. Rare side effects include pancreatitis (inflammation of the pancreas) and an increased risk of medullary thyroid CA; however, research has shown these to be very very rare and unlikely. Still, it is good to be aware, and to let your clinician know if you have a history or a family history of these.

This is one of the many pharmacological therapies available for people struggling with T2DM; in fact, I think it’s my favorite! I have seen it have wonderful effects on blood glucose levels and HbA1cs in conjunction with lifestyle and dietary changes in both T2DM and in people with prediabetes.

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