Mirabegron + Tadalafil for Prediabetes

Recruiting in Palo Alto (17 mi)

Overseen by Philip Kern, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Philip Kern

Must not be taking: Antidiabetics, Steroids, NSAIDs, Anticoagulants

Disqualifiers: Diabetes, Unstable conditions, Inflammatory, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing whether mirabegron, a drug that helps the body use sugar better, can improve blood sugar levels in obese, insulin-resistant people who are prediabetic. Mirabegron is a β3-adrenergic receptor agonist initially approved for treating overactive bladder, with potential benefits for metabolic diseases. The study also looks at whether adding tadalafil, another drug, can make mirabegron work even better. Participants will be treated for several months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using antidiabetic medications, steroids, daily NSAIDs, or anticoagulants.

Is the combination of Mirabegron and Tadalafil safe for humans?

Tadalafil, also known as Cialis, is generally safe for humans and is well tolerated, even in people with heart conditions. Common side effects include mild headaches, indigestion, and back pain, but serious heart-related issues are not common. ^{1 2 3 4 5}

How is the drug Mirabegron + Tadalafil unique for prediabetes?

Mirabegron + Tadalafil is unique for prediabetes as it combines two drugs typically used for other conditions: Mirabegron, which is used for overactive bladder, and Tadalafil, known for treating erectile dysfunction. This combination is novel for prediabetes, as there are no standard treatments specifically targeting this condition. ^{6 7 8 9 10}

Research Team

Philip Kern, M.D.

Principal Investigator

University of Kentucky

Eligibility Criteria

This trial is for adults with prediabetes, characterized by a Hemoglobin A1C level of 5.7 to 6.4 and a body mass index (BMI) between 27 and 45. It's not suitable for those with contraindications to mirabegron or tadalafil, users of steroids/NSAIDs/anticoagulants regularly, people with chronic inflammation, diabetes, on antidiabetic meds, or any unstable medical condition.

Inclusion Criteria

Your body mass index is between 27 and 45.

Your hemoglobin A1C level is between 5.7 and 6.4.

Exclusion Criteria

I use steroids or NSAIDs every day.

I cannot take mirabegron or tadalafil due to health reasons.

I am currently taking blood thinners.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Procedures

Baseline procedures conducted before treatment initiation

1-2 weeks

Treatment

Participants receive mirabegron, tadalafil, both, or placebo for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Mirabegron (Beta-3 Agonist)
• Placebo (Drug)
• Tadalafil (Phosphodiesterase Type 5 Inhibitor)

Trial Overview The study tests if mirabegron (a drug that activates ß3 receptors) alone or combined with tadalafil (commonly used for erectile dysfunction), can improve blood sugar control in prediabetics over placebo after 14 weeks. The goal is to see if these treatments can reverse prediabetes in obese individuals resistant to insulin.

Participant Groups

Group I: Tadalafil (T) Experimental Treatment 1 Intervention

Drug will be administered for 12 weeks after baseline procedures.

Group II: Mirabegron and Tadalafil (MT) Experimental Treatment 2 Interventions

Both drugs will be administered for 12 weeks after baseline procedures.

Group III: Mirabegron (M) Experimental Treatment 1 Intervention

Drug will be administered for 12 weeks after baseline procedures.

Group IV: Placebo (P) Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Philip Kern

Lead Sponsor

Trials

8

Recruited

450+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

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

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

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

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

Tadalafil is generally safe and well-tolerated for chronic treatment of erectile dysfunction, even in high-risk populations, with most side effects being mild or moderate and reversible without stopping the medication.

It does not increase the risk of cardiovascular issues and can be safely used alongside antihypertensive medications and selective alpha-receptor blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and tolerance of tadalafil in the treatment of erectile dysfunction]. He, XY.[2015]

Vardenafil significantly improved erectile function in aged men with diabetes, as shown by increased scores on the IIEF and EQS scales after 8 weeks of treatment, with scores rising from 8.1 to 18.9 for IIEF in the diabetic group.

The treatment was well tolerated, with a total effectiveness rate of 65% in the diabetic group and 73.3% in the non-diabetic group, indicating that vardenafil is a viable option for managing erectile dysfunction in older men, particularly those with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vardenafil significantly alleviates erectile dysfunction in aged men with diabetes]. Zhang, ZL., Li, HJ., Zhen, WH., et al.[2015]

IC351 (tadalafil) is a highly selective PDE-5 inhibitor with efficacy rates of up to 93% for successful intercourses in patients with mild to moderate erectile dysfunction, based on a European daily-dosing trial.

The drug has a long half-life of over 17 hours, allowing for greater spontaneity in sexual activities, and while it can cause mild to moderate side effects like headaches and dyspepsia, serious adverse events were not reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IC351 (tadalafil, Cialis): update on clinical experience. Porst, H.[2015]

In a study of 216 men with diabetes and erectile dysfunction, tadalafil significantly improved erectile function and related sexual performance measures over 12 weeks, regardless of their blood sugar levels.

Tadalafil was well tolerated, with only mild side effects like headache and dyspepsia reported, and it did not affect blood sugar control, making it a safe option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of tadalafil on erectile dysfunction in men with diabetes. Sáenz de Tejada, I., Anglin, G., Knight, JR., et al.[2023]

Tadalafil, a PDE-5 inhibitor, is effective for treating erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia, showing good tolerance in patients.

The drug is considered safe for patients with cardiovascular comorbidities and may even provide beneficial effects on cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of tadalafil in patients with cardiovascular comorbidities]. Nikitina, IL., Gaysina, GG., Galimov, SN., et al.[2019]

IDegLira, a combination of insulin degludec and liraglutide, effectively lowers blood glucose levels in Type 2 diabetes patients while minimizing the risk of hypoglycemia and weight gain.

Clinical studies indicate that IDegLira is beneficial for both insulin-naive patients and those who struggle to maintain good glycemic control on basal insulin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can a fixed-ratio combination of insulin degludec and liraglutide help Type 2 diabetes patients to optimize glycemic control across the day? Simpson, R., King, A.[2015]

In a study of 629 patients with type 2 diabetes who switched to the fixed-ratio combination of insulin Degludec and Liraglutide (IDegLira), significant reductions in HbA1c levels were observed across all treatment subgroups, indicating effective glucose control.

Patients previously treated with GLP-1RA alone or in combination with basal insulin experienced weight gain after starting IDegLira, while those switching from basal insulin or multiple daily injections lost weight, highlighting the varied effects of IDegLira on body weight depending on prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initiation of the Fixed Combination IDegLira in Patients with Type 2 Diabetes on Prior Injectable Therapy: Insights from the EASY French Real-World Study. Tramunt, B., Disse, E., Chevalier, N., et al.[2022]

Sildenafil oral spray significantly improved erectile dysfunction (ED) in men with type 2 diabetes and prediabetes, as evidenced by increased International Index of Erectile Function (IIEF-5) scores after one month of treatment.

The treatment also led to beneficial metabolic changes, including weight loss and improved insulin levels, without altering existing diabetes medications, indicating a dual benefit for patients with ED and metabolic issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of Sildenafil oral spray for the treatment of erectile dysfunction in patients with type 2 diabetes mellitus and prediabetes]. Korenkov, DG., Tumanov, DV., Kuprin, NI.[2023]

In a study involving 260 patients with type 2 diabetes, the combination therapy IDegLira significantly improved postprandial glucose control compared to insulin degludec, showing a greater reduction in glucose levels after meals.

IDegLira also enhanced endogenous insulin secretion and beta cell function, which contributed to its effectiveness, while maintaining the benefits of liraglutide across all main meals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test. Holst, JJ., Buse, JB., Rodbard, HW., et al.[2018]

In a 26-week trial involving 413 patients with type 2 diabetes, the combination of insulin degludec and liraglutide (IDegLira) resulted in a significant A1C reduction of 1.9%, compared to a 0.9% reduction with insulin degludec alone, demonstrating superior glycemic control.

IDegLira also led to an average weight loss of 2.7 kg, while insulin degludec alone showed no weight change, and both treatments had similar rates of hypoglycemia, indicating that IDegLira is effective and safe for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). Buse, JB., Vilsbøll, T., Thurman, J., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Safety and tolerance of tadalafil in the treatment of erectile dysfunction]. [2015]

2. China pubmed.ncbi.nlm.nih.gov

[Vardenafil significantly alleviates erectile dysfunction in aged men with diabetes]. [2015]

3. England pubmed.ncbi.nlm.nih.gov

IC351 (tadalafil, Cialis): update on clinical experience. [2015]

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

Effects of tadalafil on erectile dysfunction in men with diabetes. [2023]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Safety of tadalafil in patients with cardiovascular comorbidities]. [2019]

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

Can a fixed-ratio combination of insulin degludec and liraglutide help Type 2 diabetes patients to optimize glycemic control across the day? [2015]

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

Initiation of the Fixed Combination IDegLira in Patients with Type 2 Diabetes on Prior Injectable Therapy: Insights from the EASY French Real-World Study. [2022]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Efficacy of Sildenafil oral spray for the treatment of erectile dysfunction in patients with type 2 diabetes mellitus and prediabetes]. [2023]

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

IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test. [2018]

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

Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). [2022]