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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether fluoxetine (Prozac), a common antidepressant, can help people with Type 1 Diabetes exercise without worrying about low blood sugar. Researchers believe fluoxetine might improve the body's stress responses during exercise, making it safer and more beneficial for those with Type 1 Diabetes. Participants will take either fluoxetine or a placebo for six weeks, then exercise again to observe any differences. Ideal candidates have Type 1 Diabetes, no serious diabetes-related complications, and concerns about low blood sugar during exercise. As an Early Phase 1 trial, this research aims to understand how fluoxetine works in people with Type 1 Diabetes, offering participants a chance to contribute to groundbreaking insights.

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.

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

Research has shown that fluoxetine, also known as Prozac, is generally safe for use. Studies have found that taking fluoxetine for six weeks can help manage blood sugar levels and improve the body's response to low blood sugar. This is important for people with diabetes who want to exercise without worrying about their blood sugar dropping too low.

Fluoxetine is a type of medication called an SSRI, often used to treat depression. However, it also helps control blood sugar and weight. Research indicates that fluoxetine can reduce body weight and lower fasting blood sugar in people with glucose processing issues. One study found that fluoxetine does not increase the short-term risk of developing type 2 diabetes compared to other similar medications.

Overall, these findings suggest that fluoxetine is safe and may offer extra benefits for those managing diabetes. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetes?

Unlike the standard treatments for Type 1 Diabetes, which typically focus on insulin replacement and glucose management, fluoxetine is being explored for its potential to improve glycemic control through a different pathway. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI), commonly used as an antidepressant, and researchers are interested in its ability to reduce inflammation and preserve insulin-producing beta cells. This novel approach could offer additional benefits in managing Type 1 Diabetes, potentially enhancing the quality of life for patients beyond the effects of traditional treatments.

What evidence suggests that fluoxetine might be an effective treatment for Type 1 Diabetes?

Research has shown that fluoxetine, a type of medication known as an SSRI, might help manage Type 1 diabetes by affecting how the body handles stress. In this trial, participants in one arm will receive fluoxetine, while those in another arm will receive a placebo. Studies have found that fluoxetine can boost the activity of the sympathetic nervous system, which helps the body respond to stress and exercise. This system plays a crucial role in controlling blood sugar during physical activity. Some research also suggests that fluoxetine can improve blood sugar control and assist with weight management in people with diabetes. These effects make fluoxetine a promising option for managing blood sugar levels during exercise, potentially lowering the risk of low blood sugar (hypoglycemia) that might prevent people with diabetes from exercising. ^{1 2 5 6 7}

Who Is on the Research Team?

Stephen N. Davis, MBBS

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

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

I have been diagnosed with Type 1 Diabetes.

Your HbA1c level is between 6% and 10%.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2584138/

Effects of the Selective Serotonin Reuptake Inhibitor ... Our results demonstrate that a period of 6 weeks of high-dose fluoxetine significantly increases sympathetic nervous system, HPA, and metabolic (EGP and ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/10834419/

Fluoxetine for depression in diabetes: a randomized ... - PubMed Conclusions: Fluoxetine effectively reduces the severity of depression in diabetic patients. Our study demonstrated that after only 8 weeks, this treatment also ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1876201822000909

Effects of the selective serotonin reuptake inhibitor ... Conclusion: Fluoxetine had a positive effect on improving blood glucose control in patients with disorders of glucose metabolism and was good for weight ...

4. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-07441-8

The impact of fluoxetine on obesity and diabetes-related ... Our meta-analysis of RCTs examining fluoxetine's effects on obesity and diabetes-related biomarkers found significant reductions in BW, FBS, ...

5. diabetesjournals.org diabetesjournals.org/diabetes/article/57/9/2453/15528/Effects-of-a-Selective-Serotonin-Reuptake

Effects of a Selective Serotonin Reuptake Inhibitor, Fluoxetine ... Several reports have indicated that fluoxetine could have metabolic effects and influence carbohydrate metabolism (1–3).

6. psychiatry-psychopharmacology.com psychiatry-psychopharmacology.com/Content/files/sayilar/138/PCP_20240917_nlm_new_indd.pdf

Short Term Risk of Type 2 Diabetes in Patients Using ... Conclusion: The short-term risk of T2D was significantly higher in the milnacipran and venlafaxine groups than in the fluoxetine group. All ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18835927/

Effects of the selective serotonin reuptake inhibitor fluoxetine ... Conclusions: This study has demonstrated that 6-week administration of the SSRI fluoxetine can amplify ANS and metabolic counterregulatory mechanisms during ...