What does diazoxide do? Unpacking the functions of a versatile medication

October 6, 2025 •

4 min read

Diazoxide, also known by the brand name Proglycem®, is a first-line pharmacologic therapy for many patients with hyperinsulinism, a condition causing dangerously low blood sugar. The question of what does diazoxide do is answered by understanding its unique dual mechanism: inhibiting insulin secretion for hypoglycemia and historically acting as a vasodilator.

Quick Summary

Diazoxide is a medication that primarily inhibits the release of insulin from the pancreas to manage symptomatic hypoglycemia caused by hyperinsulinism. It achieves this by activating potassium channels in pancreatic cells. It was also historically used as an intravenous vasodilator for hypertensive emergencies, but this formulation is no longer available in the U.S.

Key Points

Inhibits Insulin Release: Diazoxide activates potassium channels on pancreatic cells, preventing the release of insulin and thus raising blood sugar levels.
Treats Hyperinsulinemic Hypoglycemia: The medication is used to manage low blood sugar caused by excessive insulin secretion from conditions like insulinomas and congenital hyperinsulinism.
Dual Action (Historical vs. Current): While the oral form inhibits insulin release, a now-discontinued intravenous version was used as a potent vasodilator for hypertensive emergencies.
Common Adverse Effects: Side effects include significant fluid retention, excessive hair growth (hirsutism), and gastrointestinal issues.
Risk in Neonates: In newborns and infants, diazoxide carries a specific risk of pulmonary hypertension, requiring careful cardiac monitoring.
Requires Close Monitoring: Patients need regular checks of blood glucose, electrolytes, and blood cell counts to manage the medication effectively and safely.

The Dual Action of Diazoxide

Diazoxide, a non-diuretic benzothiadiazine derivative, is a unique medication with two primary actions, though only one is currently relevant in the U.S. clinical setting. The oral form, marketed under brand names like Proglycem®, primarily raises blood glucose by inhibiting insulin release from the pancreas. The intravenous form, once used for hypertensive emergencies, acted as a potent vasodilator but is no longer available. Understanding this dual mechanism is key to appreciating its specific medical applications.

Inhibiting Insulin Release to Treat Hypoglycemia

For managing low blood sugar (hypoglycemia) caused by excessive insulin secretion, diazoxide works at the cellular level by interacting with the ATP-sensitive potassium channels ($K{ATP}$ channels) located on the surface of pancreatic beta ($eta$) cells. Normally, when blood glucose levels rise, the beta cells close these $K{ATP}$ channels, which leads to cell depolarization and triggers the release of insulin. Diazoxide does the opposite: it activates and holds these channels open. This causes the beta cells to remain hyperpolarized, preventing the influx of calcium ions necessary for insulin secretion. By blocking the release of insulin, diazoxide effectively raises blood glucose concentrations, making it a crucial tool for managing conditions that cause hyperinsulinism.

Historical Use as a Vasodilator

Intravenous (IV) diazoxide was historically used to lower blood pressure in hypertensive emergencies. This effect was due to its action as a direct arterial vasodilator, causing smooth muscle relaxation and reducing peripheral vascular resistance. Importantly, the oral formulations used to treat hypoglycemia do not produce this significant blood pressure-lowering effect. The IV formulation is no longer available on the U.S. market, focusing modern clinical use exclusively on its anti-hypoglycemic properties.

Clinical Applications and Indications

Oral diazoxide is prescribed for several conditions characterized by hyperinsulinism that result in symptomatic hypoglycemia. These include both adults and pediatric patients, including newborns and infants.

Congenital Hyperinsulinism (CHI): The most common cause of persistent hypoglycemia in infants and children, diazoxide is a first-line treatment for patients with a specific genetic form of CHI where the $K_{ATP}$ channels are responsive.
Insulinoma: A tumor of the pancreas that secretes excessive insulin. Diazoxide is often the first choice of medical therapy for patients with inoperable insulinomas to prevent or manage hypoglycemic episodes.
Nesidioblastosis: This condition involves diffuse pancreatic beta cell hypertrophy, leading to hyperinsulinism. Diazoxide may be used to manage hypoglycemia in adult or pediatric patients.
Prader-Willi Syndrome (PWS): A new extended-release formulation has been approved for treating hyperphagia (an insatiable appetite) in patients with PWS.

Potential Side Effects and Monitoring

Because of its systemic effects, diazoxide therapy requires close monitoring to manage potential side effects. The most common and serious side effect is sodium and fluid retention, which can lead to edema and potentially congestive heart failure, especially in vulnerable patients. Other adverse reactions are also common and include:

Cardiovascular: Tachycardia, palpitations, and, rarely, pulmonary hypertension in neonates.
Dermatological: Hirsutism (excessive hair growth) is a common, often reversible side effect, particularly in children and women.
Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea, and loss of appetite.
Hematological: Neutropenia and thrombocytopenia have been reported and necessitate regular blood count monitoring.
Metabolic: Hyperglycemia or ketoacidosis can occur, especially in diabetic patients or during illness.

To mitigate these risks, patients taking diazoxide must be regularly monitored. This includes checking blood glucose levels, serum electrolytes, uric acid, and complete blood counts. In infants and newborns, cardiac function should be carefully monitored, and an echocardiogram may be performed before and during treatment to screen for pulmonary hypertension. Often, a thiazide diuretic is co-administered to counteract fluid retention.

Comparison of Diazoxide with Other Hyperinsulinism Treatments

While diazoxide is a standard first-line treatment for certain types of hyperinsulinism, alternative therapies exist, each with its own mechanism and profile. Below is a comparison table outlining key differences between diazoxide and somatostatin analogs, such as octreotide and lanreotide, which are also used for treating hyperinsulinemia.


Feature	Diazoxide (e.g., Proglycem)	Somatostatin Analogs (e.g., Octreotide)
Mechanism	Activates $K_{ATP}$ channels, inhibiting insulin release.	Acts on somatostatin receptors to suppress insulin and glucagon release.
Route of Administration	Oral suspension or capsules.	Subcutaneous or intravenous injection.
Adverse Effects	Fluid retention, hirsutism, hyperglycemia, neutropenia, pulmonary hypertension in neonates.	Gastrointestinal issues (diarrhea, nausea), gallstones, fat malabsorption.
First-Line Role	Yes, for responsive forms of hyperinsulinism with intact $K_{ATP}$ channel function.	Typically used as an alternative for patients who are unresponsive to or intolerant of diazoxide.
Efficacy	Effective for many types of hyperinsulinism, particularly those with functional $K_{ATP}$ channels.	Effective in many cases, especially when diazoxide fails or for specific tumor types like insulinoma.

Conclusion

In summary, what does diazoxide do primarily revolves around its use as a hyperglycemic agent for managing severe, persistent hypoglycemia caused by hyperinsulinism in both children and adults. Its mechanism of opening pancreatic $K_{ATP}$ channels to suppress insulin release makes it an effective tool for conditions like congenital hyperinsulinism and insulinomas. While it once served a dual role as a vasodilator, that intravenous formulation is no longer commercially available in the U.S., simplifying its modern clinical identity. The medication requires careful monitoring for potential side effects, notably fluid retention and specific risks in infants, which underscores the importance of close collaboration with a healthcare team. Alternatives exist, but diazoxide remains a key player in the treatment algorithm for hyperinsulinemia. You can find more information about diazoxide and its effects on the body through medical resources like the Mayo Clinic's guide to oral diazoxide.

Frequently Asked Questions

Diazoxide raises blood sugar by binding to and activating ATP-sensitive potassium ($K_{ATP}$) channels in the beta cells of the pancreas. This activation prevents the beta cells from releasing insulin, leading to an increase in blood glucose concentration.

No, the intravenous form of diazoxide that was once used for hypertensive emergencies is no longer available in the U.S. market. The oral form used for hypoglycemia does not have a significant blood pressure-lowering effect.

The most common and clinically significant side effect is sodium and fluid retention, which can cause swelling (edema) and may require concurrent treatment with a diuretic.

Hirsutism, or excessive hair growth on the face, arms, and back, is a common adverse effect associated with diazoxide therapy, particularly in women and children. The hair growth is reversible once the medication is stopped.

No, diazoxide is contraindicated for treating functional hypoglycemia, which is caused by dietary factors rather than an underlying medical condition causing excessive insulin release.

Monitoring includes frequent checks of blood glucose levels, blood cell counts, serum uric acid, and electrolytes. In neonates, careful cardiac monitoring via echocardiogram is also necessary to screen for pulmonary hypertension.

If a patient develops fluid retention, a healthcare provider may prescribe a thiazide diuretic, such as hydrochlorothiazide, to counteract this effect and help the body excrete the excess sodium and water.