What is the likelihood of developing secondary adrenal insufficiency in a patient experiencing hypoglycemia while on maximum dose of Ozempic (semaglutide) eight years after gastric bypass surgery?

From the Guidelines

The likelihood of developing secondary adrenal insufficiency in a patient experiencing hypoglycemia while on maximum dose of Ozempic (semaglutide) eight years after gastric bypass surgery is low to moderate.

Key Factors

• The patient is on semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), which is not directly associated with adrenal insufficiency, but caution is advised in patients with prior gastric surgery 1.
• The patient has a history of gastric bypass surgery, which may increase the risk of hypoglycemia, but is not a direct cause of adrenal insufficiency.
• Hypoglycemia can be a trigger for adrenal crisis in patients with adrenal insufficiency, but the patient's current condition is not explicitly stated to be related to adrenal insufficiency.

Adrenal Insufficiency Risk

• Secondary adrenal insufficiency is typically caused by deficient adrenocorticotropin hormone secretion by the pituitary gland or deficient corticotropin-releasing hormone secretion by the hypothalamus 1.
• The patient's hypoglycemia while on semaglutide may be related to the medication's effects on glucose metabolism, but it is not a direct indicator of adrenal insufficiency.

Management Considerations

• Patients with adrenal insufficiency require stress doses of hydrocortisone during periods of physiological stress, such as surgery or illness 1.
• However, there is no clear indication that the patient in question has adrenal insufficiency or requires stress doses of hydrocortisone.

Conclusion Not Provided as per Guidelines

Instead, the key points to consider are:

• Monitor the patient's condition closely for signs of adrenal crisis, such as hypotension, hypoglycemia, and electrolyte imbalances.
• Consider the patient's medical history, including the gastric bypass surgery, and adjust management accordingly.
• Be aware of the potential risks and benefits of semaglutide in patients with prior gastric surgery, and adjust the treatment plan as needed 1.

The FDA Drug Labels for semaglutide (PO) do not address this question.

From the Research

Secondary Adrenal Insufficiency and Hypoglycemia

• The likelihood of developing secondary adrenal insufficiency in a patient experiencing hypoglycemia while on maximum dose of Ozempic (semaglutide) eight years after gastric bypass surgery is a complex issue, as evidenced by 2, which describes reversible adrenal insufficiency in three patients with post-Roux-en-Y gastric bypass noninsulinoma pancreatogenous hypoglycemia syndrome.
• According to 2, hyperinsulinemic hypoglycemia can predispose to attenuation of counterregulatory hormone responses to hypoglycemia, and consequent suppression of the hypothalamic-pituitary-adrenal (HPA) axis, which may lead to secondary adrenal insufficiency.
• The study 2 suggests that transient adrenal insufficiency is a potential complication in patients who experience recurrent hyperinsulinemic hypoglycemia after gastric bypass surgery.

Diagnostic Approach

• The diagnosis of secondary adrenal insufficiency is complex, as no single test has sufficient sensitivity to identify all patients with this condition, as stated in 3 and 4.
• A 3-step diagnostic approach is recommended, starting with the 8 AM basal cortisol determination in conjunction with either the low-dose cosyntropin stimulation test (LST) or the high-dose cosyntropin stimulation test (HST), as suggested in 4.
• Further assessment with the overnight metyrapone test (OMT) or insulin tolerance test (ITT) may be necessary in cases of an indeterminate response coupled with a strong clinical suspicion, as mentioned in 4.

Role of Semaglutide

• Semaglutide, a long-acting GLP1 receptor agonist, has been shown to be effective in reducing episodes of reactive hypoglycemia in patients with dumping syndrome after bariatric surgery, as reported in 5.
• However, the relationship between semaglutide and the development of secondary adrenal insufficiency is not well established, and further research is needed to understand this potential association.

Glycometabolic Alterations

• Secondary adrenal insufficiency is associated with glycometabolic alterations, including impaired glucose tolerance and diabetes mellitus, as discussed in 6.
• Glucocorticoid replacement therapy may play a role in these alterations, and novel regimen schemes and GC preparations have been introduced to improve compliance and better mimic endogenous cortisol rhythm, as reviewed in 6.