Hypoglycemia, or low blood sugar, happens when blood glucose drops below roughly 70 mg/dL, though most people don’t feel symptoms until it falls below 55 mg/dL. The causes range from common medication side effects to rare tumors, and they differ significantly depending on whether you have diabetes.
Diabetes Medications Are the Most Common Cause
The single biggest driver of hypoglycemia is diabetes treatment itself. Insulin is the most obvious culprit: too high a dose, mistimed injections, or skipping a meal after taking insulin can all send blood sugar plummeting. But insulin isn’t alone. Sulfonylureas and meglitinides, two classes of oral diabetes pills, work by forcing the pancreas to release insulin regardless of how much glucose is in your blood. That unregulated insulin release is what makes them risky.
Other common diabetes drugs carry much lower risk on their own. Metformin, GLP-1 receptor agonists (like semaglutide), SGLT2 inhibitors, and DPP-4 inhibitors don’t trigger uncontrolled insulin secretion, so they rarely cause hypoglycemia when used alone. The risk climbs, however, when any of these are combined with insulin or a sulfonylurea. If you’re on multiple diabetes medications and experiencing low blood sugar episodes, the combination is usually the problem.
People with diabetes can also experience symptoms at higher glucose levels than someone without diabetes. Chronic high blood sugar shifts the body’s “set point” for recognizing a low, so someone whose blood sugar routinely runs in the 200s may feel hypoglycemic at 90 mg/dL, even though that’s technically a normal reading.
Alcohol and the Liver’s Glucose Supply
Your liver is your body’s main glucose warehouse. It stores sugar as glycogen and converts other molecules into glucose through a process called gluconeogenesis. Alcohol disrupts both of these functions. When the liver breaks down alcohol, it shifts its internal chemistry in a way that blocks the key steps needed to produce new glucose. Essentially, the liver gets so busy processing alcohol that it stops releasing sugar into your bloodstream.
This effect is worse on an empty stomach or after heavy drinking, because glycogen reserves are already low. Alcohol also suppresses the shivering reflex, which means your body’s backup system for generating energy in response to low blood sugar doesn’t kick in as effectively. The result: blood sugar can drop dangerously, sometimes hours after the last drink, when the person may be asleep or appear simply intoxicated to bystanders.
Reactive Hypoglycemia After Meals
Some people experience low blood sugar not from fasting, but two to four hours after eating. This is called reactive (or postprandial) hypoglycemia. It happens when the body overshoots its insulin response to a meal, producing more insulin than necessary and driving blood sugar below normal.
One well-documented trigger is gastric bypass or other bariatric surgery. After these procedures, food moves into the small intestine faster than normal, causing a rapid spike in blood sugar followed by an exaggerated insulin surge and a subsequent crash. In people who haven’t had surgery, the cause is often harder to pin down. Some cases are linked to prediabetes, where early insulin resistance leads to delayed but excessive insulin release. Others remain idiopathic, meaning no clear underlying cause is found.
Organ Failure and Critical Illness
Severe illness can overwhelm the body’s ability to maintain stable blood sugar. The mechanisms differ depending on which organ is failing.
In liver failure, the problem is straightforward: the liver can’t store enough glycogen or manufacture new glucose. Since the liver normally supplies most of the glucose your brain and muscles use between meals, losing that capacity creates a direct shortage.
Kidney failure works differently. The kidneys contribute about 20% of the body’s glucose production, so as kidney function declines, that contribution shrinks. On top of that, the kidneys are responsible for clearing insulin from the blood. When filtration drops below a certain threshold, insulin lingers longer than it should, pushing blood sugar lower. Malnutrition and muscle wasting, common in advanced kidney disease, further reduce the raw materials available for glucose production. Acidosis from kidney failure also limits the liver’s ability to compensate.
Severe infections, including sepsis and cerebral malaria, can cause hypoglycemia through a combination of increased glucose consumption by the body (and, in malaria, possibly by the parasites themselves) and impaired glucose production.
Hormone Deficiencies
Several hormones work together to keep blood sugar from dropping too low. When any of these are deficient, the safety net weakens.
- Cortisol deficiency (adrenal failure): Cortisol signals the liver to produce glucose and reduces how sensitive your tissues are to insulin. Without enough cortisol, your body makes less glucose and responds more strongly to whatever insulin is present, a double hit.
- Growth hormone deficiency (pituitary failure): Growth hormone counterbalances insulin’s effects. When the pituitary gland fails, both cortisol-stimulating hormones and growth hormone can drop, leaving the body unable to mount a normal defense against falling blood sugar.
These hormonal causes are uncommon but important to identify because they’re treatable with hormone replacement.
Insulin-Producing Tumors
An insulinoma is a rare tumor of the pancreas that continuously secretes insulin, regardless of blood sugar levels. Because the tumor operates outside the body’s normal feedback loops, it keeps driving glucose down even when you haven’t eaten. The classic pattern is fasting hypoglycemia: episodes that worsen the longer you go without food, with symptoms like confusion, shakiness, and sweating that resolve quickly after eating.
Diagnosis typically involves a supervised fast lasting up to 72 hours in a hospital, during which doctors look for an abnormal combination: blood sugar below 50 mg/dL alongside inappropriately high insulin levels. Insulinomas are almost always benign and curable with surgery.
A separate category, non-islet cell tumors, can also cause hypoglycemia. These are typically large tumors (often in the abdomen or chest) that produce a substance similar enough to insulin that it activates the same receptors. This is less common than insulinoma but follows a similar pattern of recurrent, unexplained low blood sugar.
Other Overlooked Triggers
A few causes don’t fit neatly into the categories above but are worth knowing about.
Anorexia nervosa and prolonged starvation deplete the liver’s glycogen stores. Once those reserves are gone, the body relies entirely on gluconeogenesis, which requires amino acids from muscle tissue. In severe malnutrition, even that backup system fails.
Certain non-diabetes medications can occasionally cause hypoglycemia. Some antibiotics (particularly a class of fluoroquinolones), beta-blockers, and quinine have all been linked to low blood sugar episodes, especially in people with other risk factors like kidney disease or poor nutrition.
Autoimmune hypoglycemia is rare but real. In this condition, the immune system produces antibodies against insulin or insulin receptors. These antibodies can cause unpredictable surges of insulin activity, leading to sudden and sometimes severe drops in blood sugar. It’s most often seen in people who already have another autoimmune condition.