Is a mild elevation in platelet count a possible side effect of Glucagon-like peptide-1 (GLP-1) receptor agonists?

Mild Elevation in Platelet Count as a Possible Side Effect of GLP-1 Receptor Agonists

GLP-1 receptor agonists can decrease platelet aggregation, but there is no strong evidence indicating they cause mild elevation in platelet counts as a side effect. 1

Mechanism of Action and Platelet Effects

• GLP-1 receptor agonists primarily work by enhancing insulin secretion, reducing glucagon release, slowing gastric emptying, and decreasing appetite 2
• These medications have been found to decrease systemic inflammation and platelet aggregation rather than increase platelet counts 1
• Full-length GLP-1 receptors have been identified on megakaryocytes (platelet precursor cells), suggesting direct effects on platelet function 3
• Exenatide has been shown to inhibit thrombin-, ADP-, and collagen-induced platelet aggregation in laboratory studies 3

Cardiovascular and Hematologic Effects

• GLP-1 receptor agonists have demonstrated cardiovascular benefits, including reduced risk of major adverse cardiovascular events in patients with type 2 diabetes 1
• Recent research suggests GLP-1 receptor agonists may actually reduce the risk of venous thromboembolism compared to DPP-4 inhibitors 4
• The cardioprotective effects of GLP-1 receptor agonists include:
  • Improved myocardial substrate utilization
  • Anti-inflammatory and anti-atherosclerotic effects
  • Reduced myocardial ischemia injury
  • Improved endothelium-dependent vasodilation 1

Known Side Effects of GLP-1 Receptor Agonists

• The most common adverse effects are gastrointestinal, including:
  • Nausea and vomiting
  • Dyspepsia
  • Diarrhea
  • Gastrointestinal reflux
  • Constipation 1
• Other documented side effects include:
  • Cardiac arrhythmia/tachycardia (heart rate increase of 3-10 beats/min)
  • Gallbladder disorders
  • Rare cases of pancreatitis 1, 5
• A systematic review of case reports on GLP-1 agonist adverse effects identified gastrointestinal, renal, dermatologic, hepatic, and immunologic reactions, but did not report platelet count elevations 5

Clinical Implications

• When monitoring patients on GLP-1 receptor agonists, focus should be on:
  • Gastrointestinal tolerability
  • Heart rate changes
  • Renal function
  • Signs of pancreatitis 1, 6
• If a patient experiences an unexpected mild elevation in platelet count while on GLP-1 receptor agonist therapy, consider other potential causes rather than attributing it to the medication 6
• The anti-thrombotic effects of GLP-1 receptor agonists may actually be beneficial for patients at risk for cardiovascular events 3, 4

Special Considerations

• GLP-1 receptor agonists should be used with caution in patients with heart failure with reduced ejection fraction (HFrEF) and recent decompensation, as studies have shown no benefit and a trend toward worse outcomes in this population 1
• When initiating GLP-1 receptor agonists, start at a low dose and titrate slowly to minimize gastrointestinal side effects 1
• In patients with a history of pancreatitis, GLP-1 receptor agonists should be used cautiously according to American Association of Clinical Endocrinologists guidelines 1