Fluoxetine for Type 1 Diabetes

Overseen By Maka Siamashvili, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Maryland, Baltimore

Must be taking: SSRIs

Must not be taking: Beta blockers, Antidepressants

Disqualifiers: Hypertension, Heart disease, Tobacco, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

64 Participants Needed

Trial Summary

What is the purpose of this trial?

Exercise is a cornerstone of diabetes management. It helps reduce blood pressure, promote weight loss, lower insulin resistance and improve glucose and lipid (triglyceride and HDL-cholesterol) profiles. Unfortunately, the benefits of exercise are often not embraced by diabetic individuals because of the fear of low blood sugar (hypoglycemia). My laboratory has demonstrated that Autonomic nervous system (ANS) counterregulatory failure plays an important role in exercise associated hypoglycemia in Type 1 DM. ANS responses are significantly reduced in Type 1 DM and are further blunted by antecedent episodes of hypoglycemia. Furthermore, there is a large sexual dimorphism of reduced ANS responses during submaximal exercise in both Type 1 DM and healthy individuals that is unexplained. Accumulating data are demonstrating that serotonergic pathways can regulate ANS discharge. Generally, serotonergic pathways are inhibitory but both single and longer term administration of selective serotonin reuptake inhibitors (SSRI's) such as Prozac has been demonstrated to increase basal epinephrine levels and enhance baroreflex control of Sympathetic nervous system (SNS) activity. What is unknown is whether fluoxetine can also enhance SNS responses and also override the large ANS sexual dimorphism present during sub maximal exercise. Therefore, the purpose of this study is to determine if the SSRI fluoxetine (Prozac) can improve SNS responses during exercise.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including Non-selective Beta Blockers, Sedative-Hypnotics, Anticonvulsants, Antiparkinsonian drugs, Antipsychotics, Antidepressants, Mood stabilizers, CNS Stimulants, Opioids, and Hallucinogens.

What evidence supports the effectiveness of the drug fluoxetine for managing diabetes?

Research shows that fluoxetine can help with weight loss and improve blood sugar control in obese patients with type 2 diabetes, suggesting it might also help manage diabetes in other contexts. ^{1 2 3 4 5}

Is fluoxetine generally safe for humans?

Fluoxetine has been studied in various conditions and is generally considered safe for humans, with common side effects including headache, nausea, and insomnia. Serious side effects are rare, and it is well tolerated in the treatment of obesity and diabetes. ^{3 6 7 8 9}

How does the drug fluoxetine differ from other treatments for type 1 diabetes?

Fluoxetine, commonly known as Prozac, is unique because it is primarily an antidepressant that works by inhibiting serotonin reuptake, and it has been shown to promote weight loss and improve glycemic control in obese diabetic patients, which is not a typical approach for managing type 1 diabetes. ^{2 3 4 5 6}

Research Team

Stephen N. Davis, MBBS

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

This trial is for individuals aged 18-45 with Type 1 Diabetes Mellitus (DM), a body mass index under 40kg/m2, and HbA1c levels between 6-10%. Participants should not have diabetic tissue complications like retinopathy or neuropathy. Those with heart disease, hypertension, recent illnesses, on certain medications including antidepressants or anticoagulants, smokers, pregnant women, or unable to consent are excluded.

Inclusion Criteria

I am between 18-45 years old and have Type 1 diabetes.

I do not have complications from diabetes like eye or nerve issues.

I have been diagnosed with Type 1 Diabetes.

Exclusion Criteria

I am not taking medications like beta blockers, sedatives, or antidepressants.

I am unable to understand and give consent for my participation.

Pregnant women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

90 minute exercise baseline assessment

1 day

1 visit (in-person)

Treatment

Participants receive 6 weeks of treatment with either SSRI (Prozac) or placebo

6 weeks

Weekly visits (in-person)

Post-Treatment Assessment

Repeat 90 minute exercise assessment after 6 weeks of treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Fluoxetine
• Placebo control

Trial Overview The study tests if the drug Fluoxetine (Prozac) can improve the nervous system's response during exercise in people with Type 1 DM who often avoid physical activity due to fear of hypoglycemia. It compares Fluoxetine against a placebo control to see if it can override reduced autonomic responses and sexual dimorphism in exercise-related ANS activity.

Participant Groups

Group I: Trial 1-SSRI Active Control 1 Intervention

90 minute exercise baseline with 6 weeks treatment with SSRI (Prozac). Repeat 90 minute exercise after 6 week treatment.

Group II: Trial 2-Placebo Placebo Group 1 Intervention

90 minute exercise at baseline with 6 weeks treatment with placebo. Repeat 90 minute exercise after 6 weeks treatment of placebo.

Fluoxetine is already approved in United States, European Union for the following indications:

Approved in United States as Prozac for:

• Depression
• Anxiety
• Obsessive-compulsive disorder
• Bulimia nervosa
• Panic disorder

Approved in European Union as Prozac for:

• Major depressive episodes
• Obsessive-compulsive disorder
• Bulimia nervosa

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a double-blind placebo-controlled trial with 97 obese diabetic and glucose intolerant patients, those treated with 60 mg of fluoxetine daily experienced significantly greater weight loss compared to the placebo group.

Fluoxetine treatment also led to improvements in the diabetic status of the patients, indicating its potential efficacy in managing obesity-related diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine therapy in obese diabetic and glucose intolerant patients. Kutnowski, M., Daubresse, JC., Friedman, H., et al.[2022]

In a 24-week study involving 48 obese type 2 diabetics, those treated with fluoxetine lost significantly more weight (9.3 kg) compared to the placebo group (1.9 kg), indicating fluoxetine's potential efficacy for weight management in this population.

Fluoxetine treatment also led to a greater reduction in insulin dosage (46.9% decrease) compared to placebo (19.3% decrease), suggesting it may help improve insulin sensitivity in obese patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine treatment of the obese diabetic. Gray, DS., Fujioka, K., Devine, W., et al.[2022]

In a 12-month study of 40 obese patients with non-insulin-dependent diabetes, fluoxetine (60 mg daily) improved glycemic control more effectively than placebo, showing a significant reduction in plasma C-peptide and fasting glucose levels.

Fluoxetine also increased total skeletal muscle glycogen synthase activity by 31%, suggesting it enhances insulin sensitivity beyond just weight loss effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance: influence on muscle glycogen synthase and insulin receptor kinase activity. Breum, L., Bjerre, U., Bak, JF., et al.[2022]

A 15-year-old girl with congenital hyperinsulinism experienced recurrent hypoglycemia after starting fluoxetine, highlighting a potential risk of this antidepressant in patients with altered insulin regulation.

The patient's hypoglycemic episodes resolved within a week after discontinuing fluoxetine, suggesting that careful monitoring and management of antidepressant therapy is crucial in patients with conditions like congenital hyperinsulinism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine-Induced Hypoglycaemia in a Patient with Congenital Hyperinsulinism on Lanreotide Therapy. Giri, D., Price, V., Yung, Z., et al.[2018]

In a study of 48 obese type II diabetic patients, those treated with fluoxetine lost an average of 8 kg more weight than those on a placebo over 24 weeks, indicating its efficacy for weight management in this population.

Fluoxetine also significantly improved glycohaemoglobin levels and reduced daily insulin doses compared to placebo, suggesting additional metabolic benefits for obese patients with type II diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized double-blind clinical trial of fluoxetine in obese diabetics. Gray, DS., Fujioka, K., Devine, W., et al.[2022]

In a study of 30 obese subjects over 60 years old with Type 2 diabetes, fluoxetine (60 mg daily) led to significant weight loss of 2.6 kg at 3 months and 3.9 kg at 6 months, compared to minimal weight loss in the placebo group.

Fluoxetine also improved glycemic control, with a reduction in HbA1 levels by 0.9% at both 4 and 6 months, while showing no significant increase in adverse events compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study of fluoxetine in obese elderly patients with type 2 diabetes. Connolly, VM., Gallagher, A., Kesson, CM.[2022]

Fluoxetine, when used to treat obesity, has a safety profile similar to that seen in depressed patients, with most adverse events being mild and well tolerated.

No serious adverse events related to fluoxetine were identified, and special evaluations showed no major concerns regarding pharmacokinetics, psychomotor impairment, or addiction potential, indicating minimal risk associated with its use for obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of fluoxetine in the treatment of obesity. Zerbe, RL.[2014]

Fluoxetine and fluvoxamine, two selective serotonin reuptake inhibitors, significantly increase plasma glucose levels in mice, indicating a potential risk of hyperglycemia associated with these medications.

The hyperglycemic effect of fluvoxamine is linked to serotonergic mechanisms, as it was abolished by pretreatment with a serotonin depleter, while fluoxetine's effect appears to be independent of insulin changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective serotonin reuptake inhibitors fluoxetine and fluvoxamine induce hyperglycemia by different mechanisms. Yamada, J., Sugimoto, Y., Inoue, K.[2022]

Fluoxetine, a specific serotonin reuptake inhibitor, has been shown to promote weight loss in obese patients, with an average loss of about 0.5 kg per week over 6-8 weeks, and maximum weight loss typically occurring between 12-20 weeks of treatment.

In a safety analysis involving 3491 obese patients over up to 52 weeks, fluoxetine was found to be effective and well-tolerated, although some patients reported common side effects like headache, nausea, and insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical studies with fluoxetine in obesity. Wise, SD.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Fluoxetine therapy in obese diabetic and glucose intolerant patients. [2022]

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

Fluoxetine treatment of the obese diabetic. [2022]

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

Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance: influence on muscle glycogen synthase and insulin receptor kinase activity. [2022]

4. Turkey pubmed.ncbi.nlm.nih.gov

Fluoxetine-Induced Hypoglycaemia in a Patient with Congenital Hyperinsulinism on Lanreotide Therapy. [2018]

5. England pubmed.ncbi.nlm.nih.gov

A randomized double-blind clinical trial of fluoxetine in obese diabetics. [2022]

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

A study of fluoxetine in obese elderly patients with type 2 diabetes. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety of fluoxetine in the treatment of obesity. [2014]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Selective serotonin reuptake inhibitors fluoxetine and fluvoxamine induce hyperglycemia by different mechanisms. [2022]

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

Clinical studies with fluoxetine in obesity. [2018]