Mirabegron for Prediabetes

Overseen By Philip Kern, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Philip Kern

Must not be taking: Anti-diabetic medications

Disqualifiers: Diabetes, Cancer, Renal insufficiency, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 16 weeks

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether mirabegron, a medication typically used for overactive bladder, can improve glucose tolerance and affect body fat in individuals with prediabetes. Participants will undergo several tests to assess how the drug functions in their bodies, including its interaction with meals and various doses. The trial seeks individuals with prediabetes and a BMI between 27 and 45. The study involves taking blood samples and administering different doses of mirabegron or a placebo. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic anti-diabetic medication, you would not be eligible to participate.

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

Research has shown that mirabegron is generally safe and well-tolerated. It is already used to treat overactive bladder, providing some insight into its safety profile. One study found that common side effects, such as high blood pressure and urinary tract infections, decreased with higher doses.

Another study examined mirabegron's use over three years and found that many people continued using it, indicating it does not cause serious problems. Most side effects are mild and short-lived. While every treatment can have side effects, evidence suggests that mirabegron is quite safe for most people. ^{1 2 3 4 5}

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

Researchers are excited about Mirabegron for prediabetes because it works differently than most current treatments, which often focus on improving insulin sensitivity through lifestyle changes or medications that directly influence insulin levels. Mirabegron targets the beta-3 adrenergic receptors, which can increase energy expenditure and potentially improve glucose metabolism in a novel way. This unique mechanism of action may offer a new avenue for managing prediabetes, especially for those who do not respond well to traditional methods. Additionally, Mirabegron is already used for overactive bladder, which means its safety profile is relatively well-understood, adding to its appeal as a potential treatment option.

What evidence suggests that mirabegron might be an effective treatment for prediabetes?

Research has shown that mirabegron, one of the treatments studied in this trial, can improve the body's handling of sugar and insulin, making it a promising option for treating prediabetes. In individuals with difficulty processing sugar, studies found that mirabegron significantly lowered blood sugar levels. For example, blood sugar levels dropped from 165 mg/dL to 120 mg/dL after treatment. This effect likely occurs because mirabegron acts on brown fat, which helps the body use sugar more effectively. These findings suggest that mirabegron might help manage blood sugar levels in people at risk of developing diabetes. Participants in this trial may receive mirabegron or a placebo to further evaluate its effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Philip Kern, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for adults with prediabetes, characterized by slightly elevated blood sugar levels. Participants should have a BMI between 27-45 and not be on any chronic anti-diabetic medications. Those with kidney issues, cancer, unstable health conditions, inflammation or specific contraindications to Mirabegron cannot join.

Inclusion Criteria

You have a condition where your blood sugar levels are higher than normal, but not high enough for a diabetes diagnosis.

Your body mass index (BMI) is between 27 and 45.

You have difficulty with fasting or have trouble processing glucose.

Exclusion Criteria

My kidneys do not work well.

I have an ongoing inflammation condition.

My BMI is over 45.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Mirabegron or placebo for 16 weeks to assess effects on glucose metabolism and adipose tissue

16 weeks

2 visits (baseline and 16 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirabegron
• Placebo

Trial Overview The study is testing the effects of Mirabegron (a medication used for overactive bladder) on improving blood sugar control and fat tissue function in people with prediabetes compared to a placebo.

How Is the Trial Designed?

Group I: Sub-Study: Mirabegron dosing and Oral Glucose Tolerance Tests (Optional) Experimental Treatment 1 Intervention

Studies have found that larger doses of mirabegron do not elicit the same improvements in insulin sensitivity. Therefore, we aim to perform a dose-response study to gain an improved understanding of mirabegron dosing and changes in insulin sensitivity. This sub-study will have 4 total visits. visit 1 is a baseline oral glucose tolerance test. At the end of visit 1, participants will be given 6 weeks of mirabegron (25 mg) and will take 1 pill once per day for 4-6 weeks leading up to visit 2. Visit 2 will also be a standard oral glucose tolerance test. At the end of visit 2, participants will be given 6 weeks of mirabegron (50 mg) and take 1 pill once per day for 4-6 weeks leading up to visit 3. Visit 3 will also be a standard oral glucose tolerance test. At the end of visit 3, participants will be given 6 weeks of mirabegron (10 mg) and take 1 pill once per day for 4-6 weeks. Visit 4 will be the final visit and will also be a standard oral glucose tolerance test.

Group II: Sub-Study: Mirabegron and the acute response to food Experimental Treatment 1 Intervention

This sub-study will involve the recruiting of the same subjects who are eligible for this study as described above. Subjects will report to the CCTS fasting on 3 separate days. On each visit, the subject will have 5 blood draws and each blood draw will be about 8 ml, for a total of 40 ml of blood at each visit. Visit 1 will involve the participant consuming a standardized meal. At visit 2, participants will take 50mg of Mirabegron. And visit 3 will involve the participant consuming the same meal as visit 1 and also taking 50 mg of mirabegron.

Group III: Mirabegron Experimental Treatment 1 Intervention

Participants in this group will receive Mirabegron for 16 weeks.

Group IV: Placebo Placebo Group 1 Intervention

Participants in the group will receive placebo.

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 186 patients with type 2 diabetes, those switched to the insulin degludec/liraglutide (iDegLira) combination achieved a greater reduction in HbA1c levels, with 22% reaching HbA1c < 7% compared to 18.2% in the insulin glargine/lixisenatide (iGlarLixi) group after 6 months.

Patients using iDegLira also experienced significant weight loss (1.8 kg) compared to those on iGlarLixi (0.7 kg), while both groups showed similar effects on fasting and postprandial glucose levels and lipid profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct comparison two fixed-ratio combination glucagon-like peptide receptor agonist and basal insulin on glycemic and non glycemic parameters in type 2 diabetes. Risovic, I., Dumanovic, MS., Bojic, M., et al.[2023]

LixiLan (iGlarLixi) significantly reduced HbA1c levels more than insulin glargine (iGlar) in patients with type 2 diabetes, achieving a mean final HbA1c of 6.9% compared to 7.5% for iGlar, with 55% of iGlarLixi patients reaching the target of HbA1c <7.0%.

Patients using iGlarLixi experienced a decrease in body weight, while those on iGlar gained weight, with no increased risk of hypoglycemia and only mild gastrointestinal side effects, indicating a favorable safety and efficacy profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: The LixiLan-L Randomized Trial. Aroda, VR., Rosenstock, J., Wysham, C., et al.[2022]

In a study of 858 insulin-naive participants with type 2 diabetes, both insulin glargine 300 U/ml (IGlar-300) and 100 U/ml (IGlar-100) effectively reduced HbA1c and fasting plasma glucose levels in the Mild Age-Related Diabetes (MARD) and Mild Obesity Diabetes (MOD) subphenotypes after 26 weeks.

However, in the Severe Insulin Deficient Diabetes (SIDD) group, IGlar-100 was more effective than IGlar-300 in lowering HbA1c and fasting plasma glucose, and IGlar-300 was associated with a lower incidence of nocturnal hypoglycemia, indicating a potential safety advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment responses to basal insulin glargine 300 U/ml and glargine 100 U/ml in newly defined subphenotypes of type 2 diabetes: A post hoc analysis of the EDITION 3 randomized clinical trial. Landgraf, W., Owens, DR., Frier, BM., et al.[2023]

Mirabegron (50 and 100 mg) significantly improved symptoms of overactive bladder compared to placebo in a pooled analysis of three 12-week studies involving large patient groups, showing effectiveness in reducing incontinence episodes and micturitions.

The safety profile of mirabegron is favorable, with common side effects like hypertension and urinary tract infections decreasing at higher doses, and it has a lower incidence of dry mouth compared to the standard treatment, tolterodine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies. Nitti, VW., Khullar, V., van Kerrebroeck, P., et al.[2022]

The study involved 887 adults with type 2 diabetes (T2D) who were inadequately controlled on basal insulin, comparing the efficacy and safety of iGlarLixi (a combination of insulin glargine and lixisenatide) to premix insulin (BIAsp 30) over 26 weeks.

iGlarLixi demonstrated improved HbA1c reductions with a similar risk of hypoglycemia and more favorable body weight outcomes compared to BIAsp 30, suggesting it may be a better option for treatment intensification in T2D patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancing therapy with iGlarLixi versus premix BIAsp 30 in basal insulin-treated type 2 diabetes: Design and baseline characteristics of the SoliMix randomized controlled trial. McCrimmon, RJ., Al Sifri, S., Emral, R., et al.[2022]

This issue of Gateways to Clinical Trials provides a comprehensive overview of recent clinical trials involving a wide range of drugs, highlighting the importance of staying updated on new treatments and their efficacy.

The drugs listed, including well-known medications like adalimumab and bevacizumab, represent various therapeutic areas, indicating ongoing research and development in the field of medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. Bayés, M., Rabasseda, X., Prous, JR.[2014]

The document provides a comprehensive overview of recent clinical trials for a wide range of drugs, including well-known medications like adalimumab and aripiprazole, indicating ongoing research and development in various therapeutic areas.

It highlights the importance of clinical trials in evaluating the safety and efficacy of new treatments, showcasing a diverse selection of drugs that are currently being tested for their potential benefits in treating different health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. Bayés, M., Rabasseda, X., Prous, JR.[2007]

Metformin is the first-line treatment for type 2 diabetes and has been shown to have cardio-protective effects, making it a safe choice for patients with cardiovascular disease.

For patients with cardiovascular disease who need a second-line treatment, medications like empagliflozin, liraglutide, and semaglutide are recommended, while sulfonylureas (except gliclazide) should generally be avoided due to unclear cardiovascular safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Cardiovascular Effects of Older and Newer Anti-diabetic Medications. Eleftheriadou, I., Grigoropoulou, P., Liberopoulos, E., et al.[2019]

The document serves as a comprehensive guide to recent clinical trials involving a wide range of drugs, indicating a focus on the latest advancements in drug discovery and development.

It highlights various drugs, including agomelatine and others, suggesting ongoing research and potential therapeutic options across multiple medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. Bayes, M., Rabasseda, X., Prous, JR.[2007]

In a study of 199 patients with type 1 diabetes who switched to either insulin glargine 300 U/ml (Gla-300) or insulin degludec 100 U/ml (IDeg-100), both insulins showed similar overall time in range (TIR) for glucose levels, indicating comparable effectiveness in managing blood sugar during the day.

However, Gla-300 demonstrated a significantly better nocturnal glucose profile, with higher TIR at night and lower time spent above the target range compared to IDeg-100, suggesting it may offer advantages for nighttime glucose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Insulin Glargine 300 U/ml in Comparison with Insulin Degludec 100 U/ml Evaluated with Continuous Glucose Monitoring in Adults with Type 1 Diabetes and Suboptimal Glycemic Control in Routine Clinical Practice: The OneCARE Study. Conget, I., Mangas, MÁ., Morales, C., et al.[2021]

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. sciencedirect.com sciencedirect.com/science/article/pii/S0302283819307523

Safety and Efficacy of Mirabegron: Analysis of a Large ... Safety was evaluated using the proportion of treatment-emergent adverse events. Efficacy variables were derived from bladder diaries (baseline and week 12).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7379686/

Three‐year safety, efficacy and persistence data following ... High treatment persistence results were noted with mirabegron throughout the present 3‐year study. A persistence rate of 65.8% was observed after 1 year of ...