3 Things You (Still) Need to Know About GLP-1 Agonists

July 7, 2015

Incretin mimetic therapy for type 2 diabetes has been on the market for more than 10 years. Find out what you've learned about the GLP-1 agonists, here.

1. Which of the following is NOT a mechanism of action of GLP-1 receptor agonists on glucose homeostasis:

A. Stimulation of insulin secretion

B. Inhibition of glucagon secretion

C. Direct and indirect suppression of endogenous glucose production

D. Suppression of appetite

E. Enhanced insulin sensitivity secondary to weight loss

F. Delayed gastric emptying with less postprandial hyperglycemia

G. All of the above are mechanisms of action of GLP-1 receptor agonists.

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Answer: G. All of the above are mechanisms of action of GLP-1 receptor agonists. 
 

GLP-1 receptor agonists mimic the action of endogenous glucagon-like peptide 1, which has receptors in pancreas, cardiomyocytes, kidney, vascular endothelium, smooth muscle cells, and appetite centers in the brain.

 

2. GLP-1 receptor activation has been shown to improve left ventricular (LV) contractility.

A. True

B. False

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Answer: A. True. 

Animal (pig, dog, rat) studies have shown that GLP-1 agonists improve LV contractility, stroke volume and cardiac output by improving glucose utilization.  In humans, a small study with 12 patients with NYHA Class III-IV heart failure showed that a GLP-1 infusion for 5 weeks led to improvements in left ventricular ejection fraction and the 6-minute walk distance.  Improved LVEF was also noted in patients with acute MI who received a 72h GLP-1 infusion following their event.  In another randomized study of 172 patients with STEMI who were started on exenatide infusion prior to their reperfusion, the myocardial salvage index (as assessed on cardiac MRI) was significantly improved 3 month after the index event compared with those who did not receive exenatide.

 

3. Which of the following is/are physiologic, metabolic and vascular side effects of GLP-1 agonists?

A. Weight gain

B. Reduction in blood pressure

C. Increase in heart rate

D. Increase in platelet activation

E. Neutral impact on lipid panel

F. A and B

G. B and C

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Answer: G. B (reduction in blood pressure) and C (increase in heart rate)

Option A is incorrect. All GLP-1 agonists are associated with weight loss and decreased adiposity and one has been recently approved (in high doses) for treatment of obesity. Partly because of their effect on weight and partly related to other mechanisms (ie, enhanced sodium excretion), they are also associated with sustained decrease in BP of 4 to 5/1 to 2 mmHg. (Option B is correct). They are also associated with favorable effects on endothelial cells, including vasodilation. (Option D is incorrect) and a small increases in HR (2-3 beats/min) due to the presence of GLP-1 receptors on the sinoatrial node (Option C is correct).  In addition, most GLP-1 agonists result in favorable effects on lipid profile, including modest reductions in total cholesterol, LDL-C and triglycerides with small increases in HDL-C (Option E is incorrect).