Correctly identifying low blood sugar in patients without diabetes is a key step before seeking a cause for hypoglycemia, said Adrian Vella, MD, endocrinologist at the Mayo Clinic in Rochester, Minnesota, during a presentation at the American College of Physicians Internal Medicine (ACP-IM) Meeting 2026 in San Francisco.

Hypoglycemia is rare in patients without diabetes who are not on drugs for the condition, said James Flory, MD, endocrinologist at Memorial Sloan Kettering Cancer Center in New York City, who was not involved in the presentation.

Consequently, “the vast majority of patients without diabetes who are concerned about hypoglycemic episodes really have something else going on,” Flory said.

Potential causes of hypoglycemia in these patients include postprandial hypoglycemia and adrenal insufficiency, Flory said. Hypoglycemia may also occur in patients with bloodstream infections, kidney failure, starvation, alcohol abuse, or some combination of these, Flory noted.

The diagnosis of a hypoglycemic disorder requires fulfillment of the Whipple triad, which includes low levels and symptoms of plasma glucose and improvement of the symptoms corresponding to increased plasma glucose levels.

“Knowing that patients have to meet Whipple triad before further workup helps clinicians avoid subjecting patients to a long, unnecessary series of medical interventions,” Flory said.

Those who fulfill Whipple triad criteria should be further evaluated.

“The most dramatic cases I see tend to be insulinoma, proinsulinoma, non-islet-cell tumor hypoglycemia, inappropriate insulin use, and medications that cause hypoglycemia as a side effect, such as methadone,” Flory said.

Insulinoma, a rare pancreatic tumor, is the most common cause of hypoglycemia among patients without diabetes in the outpatient setting, Vella said. The condition should be assessed with CT or MRI. If results are inconclusive, as is the case in approximately 25% of cases, referral to a specialist should be made for a selective arterial calcium stimulation test.

Patients without diabetes may also have reactive hypoglycemia, which presents with symptoms such as headache after eating, dizziness, sweating, and fatigue, Vella said. The Whipple triad does not apply to this condition, and these patients often have overlap with factors related to diet and lifestyle. Dietary changes are required, such as eating smaller meals and more fiber and avoiding sugary and processed foods, he said.

Concerns about hypoglycemia among individuals without diabetes are not uncommon. Patients can monitor their glucose at home with fingerstick testing, Flory said. If a patient measures glucose levels < 55 mg/dL at home on a fingerstick and presents with symptoms meeting the Whipple triad, further workup and a likely endocrine referral are appropriate, but not until then, Flory said. 

“Continuous glucose monitoring for patients without diabetes is only a good idea if the patient will confirm any low reading with a fingerstick,” he said.

Vella disclosed serving as a consultant for Boehringer Ingelheim, Crinetics Pharmaceuticals, and Novo Nordisk. Flory reported having no financial conflicts of interest.