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GLP-1 Agonists

Date: 08/05/24

Introduction

Glucagon-Like Peptide-1 (GLP-1) agonists are a peptide hormone released from the gastrointestinal (GI) L cells after eating. Once it binds to the receptor, it causes glucose dependent insulin secretion, inhibition of glucagon release, and delay of gastric emptying. These actions improve post prandial glucose and cause an overall reduction in blood glucose. GLP-1 also causes satiety and weight loss.1

Although metformin is still the preferred first line therapy for type 2 diabetes, according to the American Diabetes Association (ADA), GLP-1 agonists should be considered for those with a hemoglobin A1c greater than 1.5% over target, patients who do not reach their target A1c in 3 months, particularly for those with atherosclerosis, chronic kidney disease, or heart failure, or for those with an intolerance or contraindication to metformin.2

Cardiovascular Benefits

People with diabetes are at risk of developing cardiovascular disease including, macrovascular complications such as myocardial infarctions (MI), heart failure, and peripheral artery disease.1 GLP-1 agonists seem to exhibit cardiovascular benefit independent of its glucose lowering activity. There are eight clinical trials examining the effectiveness of the GLP-1’s in cardiovascular disease. A meta-analysis of the eight trials demonstrated a 14% reduction of cardiovascular death, non-fatal MI, and nonfatal stroke. Currently liraglutide, semaglutide, and dulaglutide have a Food and Drug Administration (FDA) approved indication for prevention of cardiovascular disease.1

Fertility

Early studies have shown promise with the use of GLP-1 agonists for fertility outcomes related to diabetes and obesity. The early research has shown that GLP-1 may be an important modulating signal connecting the metabolic and reproductive system.3 It also appears the GLP-1 has an anti-inflammatory and anti-fibrotic effect in the gonads and endometrium that is affected by obesity.3 More research is needed to determine the role of GLP-1 agonists with preconception care for women with polycystic ovary syndrome (PCOS), obesity, and diabetes.3,4

Obesity

Obesity is a chronic medical condition defined as a body mass index (BMI) greater than or equal to 30. Interventions for weight loss include diet changes, exercise, behavior modification programs, medications, and bariatric surgery.

GLP-1 agonists by their mechanism of action, decrease appetite, increase satiety, delayed gastric emptying and GI motility which leads to weight loss.5 There are currently two GLP-1 agonists and one glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist with an FDA approved indication for weight loss: liraglutide, semaglutide, and tirzepatide. The use of GLP-1 agonists and GIP/GLP-1 agonists for weight loss is currently a benefit exclusion.

In summary, GLP-1 agonists have shown favorable outcomes with for Type 2 diabetes, and cardiovascular disease and weight loss. Future research is needed to further identify the role of GLP-1 agonists in fertility.

 

Meridian’s Preferred Drug List

Drug

FDA Approved Indication(s)

Status

Byetta™ (exenatide)

Type 2 Diabetes

Non-preferred

Bydureon BCise® (exenatide extended release)

Type 2 Diabetes

Non-preferred

Mounjaro® (tirzepatide)

Type 2 Diabetes

Preferred with Prior authorization

Ozempic® (semaglutide injectable)

Type 2 Diabetes
Reduce CV events in adults with Type 2 Diabetes

Non-preferred

Rybelsus® (semaglutide oral)

Type 2 Diabetes
Reduce CV events in adults with Type 2 Diabetes

Preferred with Prior authorization

Saxenda® (liraglutide)

Weight loss

Benefit Exclusion

Trulicity® (dulaglutide)

Type 2 Diabetes
Reduce CV events in adults with Type 2 Diabetes

Preferred

Victoza® (liraglutide)

Type 2 Diabetes
Reduce CV events in adults with Type 2 Diabetes

Preferred

Wegovy® (semaglutide)

Weight loss

Benefit Exclusion

Zepbound® (tirzepatide)

Weight loss

Benefit Exclusion

 

Effective August 15, 2024, Trulcity®, and Victoza® are preferred with a diabetes diagnosis.

Effective September 17, 2024, GLP-1 agonists are limited to one fill per 28 days.

 

References

  1. GLP-1 Receptor Agonists for the Reduction of Atherosclerotic Cardiovascular Risk in Patients with Type 2 Diabetes. Accessed July 19, 2024.
  2. Glucagon-Like Peptide -1 Receptor Agonists. Accessed July 19, 2024
  3. The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective. Accessed July 19, 2024
  4. Effects pf GLP1Ras on pregnancy rate and menstrual cyclicity in women with polycystic ovary syndrome: a meta-analysis and systematic review. Accessed July 19, 2024
  5. GLP-1 receptor agonists for the treatment of obesity: Role as a promising approach. Accessed July 19, 2024