Diazoxide for Type 2 Diabetes

Recruiting at 1 trial location

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 tests how diazoxide can control sugar production in the liver for people with type 2 diabetes. Researchers believe that activating certain brain centers with diazoxide might reduce high glucose levels, which can cause complications. The trial includes different groups: some receive diazoxide, others a placebo, and some an additional treatment called nicotinic acid. It seeks participants with type 2 diabetes who have unstable sugar levels and few diabetes-related complications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that diazoxide, the medication under study, has some known side effects. Common side effects include increased hair growth (45%), fluid retention (20%), stomach problems (13%), swelling (11%), and a decrease in certain white blood cells (9%). It can also raise blood sugar levels by slowing insulin release from the pancreas.

Diazoxide is already used for other conditions, providing researchers with some confidence about its safety. However, potential participants should consider these possible side effects when deciding to join a trial. Weigh these risks against the benefits and consult healthcare professionals before making a decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Diazoxide for Type 2 Diabetes because it works differently from standard treatments like metformin and insulin, which typically aim to improve insulin sensitivity or increase insulin production. Diazoxide, however, reduces insulin secretion by activating potassium channels in pancreatic beta cells. This unique mechanism can help manage blood sugar levels without putting added pressure on the pancreas to produce more insulin. Additionally, Diazoxide is administered orally, offering a convenient alternative to injectable treatments. This novel approach could provide a new avenue for managing blood sugar levels in people with Type 2 Diabetes.

What evidence suggests that this trial's treatments could be effective for type 2 diabetes?

Research has shown that diazoxide, one of the treatments studied in this trial, can help manage blood sugar levels by reducing insulin release. Studies indicate that diazoxide is effective for about 71% of people in similar situations, meaning it works well for many. This medication opens certain pathways in cells that control insulin release, helping to stabilize blood sugar. By doing so, diazoxide may also reduce the liver's glucose production, which is often too high in people with type 2 diabetes. This makes it a promising option for managing high blood sugar in type 2 diabetes. Participants in this trial will receive either diazoxide or a placebo, with some also receiving nicotinic acid, to evaluate its effectiveness in different contexts. ^{1 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.

Pregnant women

Subject enrolled in another study less than one month prior to the anticipated start date of the proposed study, besides those done by our group

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 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]

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]

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 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]

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 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 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7877589/

Efficacy and safety of diazoxide for treating ...

Among the cohort studies, the pooled estimate of the response rate of diazoxide therapy was 71% (95% CI 50%–93%, Pheterogeneity< 0.001, I2 = 98.3%, Peffect< ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06606327?cond=Insulin%20Resistance&aggFilters=funderType:nih%20fed,status:rec&rank=7

Diazoxide Suppression Test P&F Study (DzST)

The investigators expect that suppression of insulin secretion with diazoxide will, in accordance with the GIST, lead to no significant rise in blood glucose ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8893938/

ATP-Sensitive Potassium Channels in Hyperinsulinism and ...

By activating β-cell KATP, the KATP channel opener diazoxide suppresses electrical activity and inhibits insulin secretion. Under normal circumstances, such an ...

4.

journals.plos.org

journals.plos.org/plosone/article?id=10.1371/journal.pone.0246463

Efficacy and safety of diazoxide for treating hyperinsulinemic ...

Among the cohort studies, the pooled estimate of the response rate of diazoxide therapy was 71% (95% CI 50%–93%, Pheterogeneity< 0.001, I2 = ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01488136?term=DIAZOXIDE&viewType=Table&rank=2

NCT01488136 | Use of Diazoxide in Acute Hypoglycaemia

The investigators know that intensive insulin therapy and tight glucose control is associated with reduction of diabetic complications.

6.

drugs.com

drugs.com/medical-answers/diazoxide-proglycem-hyperglycemia-3545748/

How does diazoxide (Proglycem) cause hyperglycemia?

Oral diazoxide (Proglycem) can cause hyperglycemia (high blood sugar levels) when it works too effectively at slowing the release of insulin from the pancreas.

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0735109715043673

The Classically Cardioprotective Agent Diazoxide Elicits ...

In this study, we hypothesized that DZX prevents ischemia-mediated arrhythmias in T2DM via its putative cardioprotective and antidiabetic property.

8.

merck.ca

merck.ca/en/wp-content/uploads/sites/20/2021/04/PROGLYCEM-PM_E.pdf

PROGLYCEM®

No effect of diazoxide was noted on the blood pressure or blood sugar levels of the infants in the first 24 hours. The glucose tolerance of two ...