Diazoxide for Type 2 Diabetes

Overseen By Meredith Hawkins, M.D., M.S.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Meredith Hawkins

Must not be taking: Amphetamines, Benzodiazepines, Opiates, others

Disqualifiers: Liver disease, Kidney disease, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 7 hour infusions, 4 days in total, separated at least 1 month apart

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing diazoxide, a drug that activates parts of the brain, on people with type 2 diabetes. The goal is to see if it can help reduce the amount of glucose produced by the liver. By doing so, it may help manage high blood sugar levels in these patients. Diazoxide has been shown to improve blood sugar levels, help with weight loss, and affect certain genes in animal studies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, a negative drug screen is required, which means you cannot have certain drugs in your system. It's best to discuss your specific medications with the trial coordinators.

Is diazoxide safe for humans?

Diazoxide has been associated with several adverse effects, including hyperglycemia (high blood sugar), hyperosmolar hyperglycemic syndrome (a serious condition related to high blood sugar), pulmonary hypertension (high blood pressure in the lungs), and neutropenia (low white blood cell count). In a study, 30.5% of patients experienced at least one adverse reaction, with common issues being excessive hair growth and water retention. ^{1 2 3 4 5}

How is the drug diazoxide different from other treatments for type 2 diabetes?

Diazoxide is unique because it is primarily used to treat conditions with excessive insulin, like hyperinsulinism, by reducing insulin release, which is different from most type 2 diabetes treatments that focus on increasing insulin sensitivity or production. It can cause hyperglycemia (high blood sugar) as a side effect, which is why it is being explored for type 2 diabetes. ^{2 3 6 7 8}

Who Is on the Research Team?

Meredith Hawkins, M.D., M.S.

Principal Investigator

Albert Einstein College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 21-70 with type 2 diabetes, having an A1c level between 8.0-12.0%, and a BMI under 35 without severe diabetic complications or family history of diabetes. Healthy participants with no diabetes can also join if they meet the age, BMI, and blood sugar criteria.

Inclusion Criteria

Your blood sugar levels are normal when fasting and over time.

I am 21-70 years old, have a BMI under 35, no drug use, normal blood sugar levels, and no close family with diabetes.

My immediate family does not have a history of diabetes.

Exclusion Criteria

You smoke more than 10 cigarettes a day.

You have a significant change in your white blood cell count.

I have a blood clotting disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo pancreatic clamp studies with administration of diazoxide or placebo, with or without nicotinic acid, to assess endogenous glucose production

7 hour infusions, 4 days in total, separated at least 1 month apart

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diazoxide

Trial Overview The study tests how diazoxide affects liver glucose production in people with type 2 diabetes compared to a placebo and nicotinic acid. It aims to understand the brain's role in regulating blood sugar levels by potentially activating certain control centers.

How Is the Trial Designed?

Group I: T2D (Nicotinic Acid + placebo for diazoxide) Experimental Treatment 2 Interventions

Pancreatic clamp study will be done after lowering free fatty acids with a nicotinic acid (Niacin) infusion in type 2 diabetic participants, and after giving a taste-matched placebo for Diazoxide (Proglycem) to type 2 diabetic participants.

Group II: T2D (Diazoxide) Experimental Treatment 1 Intervention

Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to type 2 diabetic participants.

Group III: T2D (Diazoxide + Nicotinic Acid) Experimental Treatment 2 Interventions

Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to type 2 diabetic participants after lowering free fatty acids with a nicotinic acid (Niacin) infusion.

Group IV: Non-diabetic (Diazoxide) Experimental Treatment 1 Intervention

Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to non-diabetic participants.

Group V: Non-diabetic (Diazoxide + Nicotinic Acid) Experimental Treatment 2 Interventions

Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to non-diabetic participants after lowering free fatty acids with a nicotinic acid (Niacin) infusion

Group VI: Experimental: Non-diabetic (Nicotinic Acid + placebo for diazoxide) Experimental Treatment 2 Interventions

Pancreatic clamp study will be done after lowering free fatty acids with a nicotinic acid (Niacin) infusion in non-diabetic participants, and after giving a taste-matched placebo for Diazoxide (Proglycem) toon-diabetic participants.

Group VII: Non-diabetic (Placebo) Placebo Group 1 Intervention

Pancreatic clamp study will be done after giving a taste-matched placebo for Diazoxide (Proglycem) to non-diabetic participants.

Group VIII: T2D (Placebo) Placebo Group 1 Intervention

Pancreatic clamp study will be done after giving a taste-matched placebo for Diazoxide (Proglycem) to type 2 diabetic participants.

Diazoxide is already approved in United States for the following indications:

Approved in United States as Proglycem for:

• Hypoglycemia

Who Is Running the Clinical Trial?

Meredith Hawkins

Lead Sponsor

Trials

2

Recruited

110+

Albert Einstein College of Medicine

Lead Sponsor

Trials

302

Recruited

11,690,000+

American Diabetes Association

Collaborator

Trials

148

Recruited

102,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 295 infants and children treated with diazoxide for hyperinsulinism, 2.4% developed pulmonary hypertension, particularly in those with underlying risk factors like respiratory failure and structural heart disease.

The study also found a notable prevalence of other adverse events, including neutropenia (15.6%), thrombocytopenia (4.7%), and hyperuricemia (5.0%), highlighting the importance of proactive screening for these side effects in patients receiving diazoxide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Adverse Events in Children With Congenital Hyperinsulinism Treated With Diazoxide. Herrera, A., Vajravelu, ME., Givler, S., et al.[2019]

Diazoxide, a benzothiadiazine, has been shown to effectively manage hypoglycemia in frail patients, particularly those at surgical risk.

This case report highlights the successful treatment of insulinoma with diazoxide, suggesting its potential utility in similar clinical scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of insulinoma effectively treated with low-dose diazoxide. Yasuda, A., Seki, T., Kitajima, N., et al.[2020]

A 5-year-old girl developed hyperosmolar hyperglycemic syndrome (HHS) with a serum glucose level of 529 mg/dL while being treated with diazoxide and diuretics, highlighting the potential risk of hyperglycemia associated with diazoxide use.

Even at low blood levels of diazoxide (25 µg/dL), it can still lead to hyperglycemia, indicating that patients on diazoxide and diuretics require careful monitoring to prevent complications like HHS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperosmolar hyperglycemic syndrome induced by diazoxide and furosemide in a 5-year-old girl. Nakazawa, H., Naruse, Y., Mori, M., et al.[2021]

In a long-term study of 384 patients with hyperinsulinemic hypoglycemia, diazoxide effectively maintained fasting blood glucose levels above the target of 70 mg/dL for up to 4 years, demonstrating its efficacy in managing this condition.

While 30.5% of patients experienced adverse drug reactions, the most common being hypertrichosis, most side effects occurred within the first 2 months of treatment, suggesting that early monitoring is crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness, including intelligence prognosis, of diazoxide in pediatric patients with hyperinsulinemic hypoglycemia: special survey in Japan (long-term, all-case survey). Fukutomi, M., Shimodera, M., Maeda, Y., et al.[2020]

Diazoxide is the only FDA-approved treatment for neonatal hypoglycemia due to hyperinsulinism, but it has serious adverse effects, including pulmonary hypertension (2-3%) and neutropenia (15%).

A survey of pediatric endocrinologists revealed significant variability in the dosing and monitoring practices for diazoxide, leading to the development of expert consensus guidelines to standardize its use and improve safety in infants and children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management and Appropriate Use of Diazoxide in Infants and Children with Hyperinsulinism. Brar, PC., Heksch, R., Cossen, K., et al.[2021]

In a study of 56 small-for-gestational-age infants with hyperinsulinaemic hypoglycaemia, low-dose diazoxide (3-5 mg/kg/day) was found to be effective, with 96% of infants showing resolution of their condition after treatment.

The safety profile of low-dose diazoxide was excellent, with only minimal adverse effects observed, including generalized hypertrichosis in 7.4% and fluid retention in 3.7% of infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of low-dose diazoxide in small-for-gestational-age infants with hyperinsulinaemic hypoglycaemia. Chandran, S., R, PR., Mei Chien, C., et al.[2022]

In a study of 194 patients with hyperinsulinism, 85.1% were treated with diazoxide, which is the only FDA-approved medication for this condition, and the overall rate of serious adverse events (SAEs) was found to be 9.7%.

Patients with perinatal stress hyperinsulinism experienced a significantly higher rate of SAEs (16.7%) compared to those with genetic forms of hyperinsulinism (3.6%), indicating that caution is needed when prescribing diazoxide to this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of Serious Adverse Events Associated with Diazoxide Treatment of Patients with Hyperinsulinism. Thornton, P., Truong, L., Reynolds, C., et al.[2019]

In patients with insulinoma, diazoxide treatment significantly reduced serum insulin levels and improved tissue sensitivity to insulin after just three days of administration.

Before treatment, insulinoma patients showed lower metabolic clearance rates of insulin compared to controls, indicating that diazoxide effectively enhances insulin metabolism in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of euglycaemic clamping in evaluation of diazoxide treatment of insulinoma. Skrha, J., Svacina, S., Srámková, J., et al.[2019]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Prevalence of Adverse Events in Children With Congenital Hyperinsulinism Treated With Diazoxide. [2019]

2. England pubmed.ncbi.nlm.nih.gov

A case of insulinoma effectively treated with low-dose diazoxide. [2020]

3. Japan pubmed.ncbi.nlm.nih.gov

Hyperosmolar hyperglycemic syndrome induced by diazoxide and furosemide in a 5-year-old girl. [2021]

4. Japan pubmed.ncbi.nlm.nih.gov

Safety and effectiveness, including intelligence prognosis, of diazoxide in pediatric patients with hyperinsulinemic hypoglycemia: special survey in Japan (long-term, all-case survey). [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Management and Appropriate Use of Diazoxide in Infants and Children with Hyperinsulinism. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of low-dose diazoxide in small-for-gestational-age infants with hyperinsulinaemic hypoglycaemia. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Rate of Serious Adverse Events Associated with Diazoxide Treatment of Patients with Hyperinsulinism. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Use of euglycaemic clamping in evaluation of diazoxide treatment of insulinoma. [2019]