Mirabegron + Tadalafil for Prediabetes

Overseen By Philip Kern, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Philip Kern

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

Disqualifiers: Diabetes, Unstable conditions, Inflammatory, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two medications, mirabegron (Myrbetriq) and tadalafil (Cialis), in improving blood sugar control in individuals who are prediabetic and have a higher body weight. Researchers aim to determine if these medications, alone or combined, can reverse prediabetes by enhancing the body's ability to manage sugar. Participants will receive one of the medications, both, or a placebo (a pill with no active ingredients) for 12 weeks. Suitable candidates have an A1C level (a measure of blood sugar) between 5.7 and 6.4 and a body mass index (BMI) between 27 and 45, without having diabetes or taking certain medications. As a Phase 4 trial, this research involves FDA-approved treatments and seeks to understand how they can benefit more patients.

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.

What is the safety track record for these treatments?

Research has shown that both mirabegron and tadalafil are generally safe and well-tolerated. Studies on mirabegron have demonstrated its safety at doses of 25 mg, 50 mg, and 100 mg. It is commonly used to treat overactive bladder and has a strong safety record.

Tadalafil is also recognized for its safety. It is frequently used to treat erectile dysfunction and remains safe even for individuals with diabetes. Research has found that low doses of tadalafil are safe and effective for daily use.

When used together, studies indicate that the safety of these two drugs is similar to using tadalafil alone. This suggests that combining them does not introduce any new safety concerns beyond what is already known for each drug separately. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using Mirabegron and Tadalafil for prediabetes because these drugs offer a fresh approach compared to the usual lifestyle changes and medications like Metformin. Mirabegron, typically used for overactive bladder, activates brown fat tissue and boosts metabolism, which could help in managing blood sugar levels. Tadalafil, known for treating erectile dysfunction, improves blood flow and may enhance insulin sensitivity. By combining these two drugs, there's potential to tackle prediabetes in a novel way, possibly offering more effective management of the condition.

What evidence suggests that this trial's treatments could be effective for prediabetes?

Research has shown that mirabegron, one of the treatments in this trial, can improve how the body processes sugar. In one study, participants with high blood sugar levels saw a reduction from 165 mg/dL to 120 mg/dL after using mirabegron. Tadalafil, another treatment option in this trial, has shown promise in reducing the risk of developing type 2 diabetes in people with prediabetes, cutting the risk by nearly half. This trial will test the effectiveness of using mirabegron and tadalafil together, as both have been effective and well-tolerated in other conditions, suggesting they might also benefit those with prediabetes. Overall, these treatments have demonstrated positive effects on controlling blood sugar and metabolism, which are crucial for managing prediabetes. ^{2 3 5 6 7}

Who Is on the Research Team?

Philip Kern, M.D.

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Mirabegron
• Placebo
• Tadalafil

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.

How Is the Trial Designed?

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

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

Approved in United States as Myrbetriq for:

• Overactive bladder (OAB)
• Neurogenic detrusor overactivity (NDO)

Approved in European Union as Mirabegron for:

• Overactive bladder (OAB)
• Neurogenic detrusor overactivity (NDO)

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7190915/

Chronic mirabegron treatment increases human brown fat ... Besides effects on BAT, HDL cholesterol, and bile acids, mirabegron also produced substantial improvements in glucose and insulin metabolism.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7190997/

The β3-adrenergic receptor agonist mirabegron improves ... A subset of subjects had impaired glucose tolerance, and their 120-minutes glucose levels decreased from 165 mg/dL to 120 mg/dL after treatment. Among the 13 ...

3. withpower.com withpower.com/trial/phase-3-prediabetic-state-11-2020-f4310

Mirabegron for Prediabetes Mirabegron (50 and 100 mg) significantly improved symptoms of overactive bladder compared to placebo in a pooled analysis of three 12-week studies involving ...

4. scholars.uky.edu scholars.uky.edu/en/projects/mirabegron-and-tadalafil-effectiveness-for-treatment-of-prediabet

Mirabegron and Tadalafil Effectiveness for Treatment of ... We hypothesize that a 4 month treatment with the β3 agonist mirabegron will result in improved glucose metabolism in obese, prediabetic human research ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04823442

Activation of Brown Adipose Tissue Metabolism Using ... We propose that pharmacological stimulation of Beta-3 adrenergic receptor (ADBR3) at higher doses of Mirabegron may be required to elicit changes in glycemia.

6. myrbetriqhcp.com myrbetriqhcp.com/safety/

Safety | MYRBETRIQ® (mirabegron ER tablets) The safety profile of Myrbetriq has been evaluated in adult patients with overactive bladder (OAB) in three 12-week trials and a 1-year safety study.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2012/202611Orig1s000SumR.pdf

202611Orig1s000 - accessdata.fda.gov The safety data for Myrbetriq (mirabegron) to support once daily use for the treatment of overactive bladder were primarily derived from the 41 ...