Anti-Obesity Medications for Obesity

(M3 Trial)

Overseen By John M. Jakicic, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Kansas Medical Center

Must be taking: AOM

Disqualifiers: Type 2 diabetes, Pregnancy, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how obesity medications combined with exercise might alter body composition, such as fat and muscle mass, and improve overall health. It aims to determine if adding aerobic or resistance training to standard medical care, including medications like Ozempic, Wegovy, or Rybelsus, affects weight, fitness, and quality of life. Individuals who have recently started obesity medications and have a BMI over 27, particularly those with weight-related health issues like high blood pressure, may be suitable for this trial. Participants will either continue their regular medical care or include supervised workouts for six months. As an unphased trial, this study offers a unique opportunity to contribute to understanding the combined effects of medication and exercise on obesity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be newly prescribed specific anti-obesity medications (semaglutide, tirzepatide) and agree to continue them for at least 6 months.

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

Research has shown that aerobic exercise is generally safe for most people. Studies have found that engaging in at least 150 minutes of aerobic exercise each week can significantly reduce waist size and body fat. This type of exercise also enhances heart health, particularly for those who are overweight or obese.

Similarly, resistance training is safe and helps improve body shape by building and maintaining muscle while reducing fat. It also enhances the body's ability to use insulin, which is crucial for managing obesity and diabetes. Importantly, research indicates that resistance training is safe for heart health in both healthy individuals and those with heart conditions.

Both aerobic and resistance exercises are considered safe options for individuals aiming to improve their health while managing obesity. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for obesity because they integrate exercise with standard medical care, offering a more holistic approach. Unlike traditional treatments that might focus solely on medication or diet, these experimental arms include supervised aerobic or resistance training. This could enhance weight loss and improve overall health by combining physical activity with existing medical care. The addition of structured exercise might not only boost metabolism but also improve cardiovascular health and muscle strength, providing a comprehensive strategy to tackle obesity.

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

This trial will compare different approaches to managing obesity. Participants in one arm will receive Standard Medical Care plus Aerobic Training. Research has shown that aerobic exercise can greatly reduce body fat and improve heart and lung fitness. For instance, performing at least 150 minutes of aerobic exercise each week can noticeably shrink the waist and lower body fat. Another arm will involve Standard Medical Care plus Resistance Training, such as lifting weights, which effectively improves body shape by building muscle while reducing fat. Both exercise types can help individuals with obesity lose weight and enhance overall health, including heart health and muscle strength. ^{3 5 6 7 8}

Who Is on the Research Team?

Renee J. Rogers, Ph.D.

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with obesity who are interested in understanding how different types of exercise and standard medical care can affect their body composition, fitness, physical activity levels, muscle strength, blood pressure, food intake, and overall quality of life over a 6-month period.

Inclusion Criteria

I am eligible regardless of my gender or ethnicity.

Clearance from the study physician for meeting all eligibility criteria.

I am starting a new obesity treatment with AOM and agree to continue for 6 months.

Exclusion Criteria

My blood pressure is high, but I've been on stable medication for over 6 months.

Reported moderate-to-vigorous exercise for >60 min/week and >1 day of structured cardiovascular or resistance exercise over the past 3 months.

I have type 2 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are assigned to either a no exercise/standard medical care condition or a supervised exercise condition (aerobic or resistance training) for 6 months.

6 months

Initial visit, 3x per week for exercise groups, monitoring at weeks 6, 12, and 18

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aerobic Training
• Resistance Training
• Standard Medical Care

Trial Overview The study compares the effects of no exercise/standard medical care to supervised aerobic or resistance training on various health metrics. Participants will be monitored regularly and engage in exercise sessions three times a week if assigned to an exercise group.

How Is the Trial Designed?

Group I: Standard Medical Care plus Resistance Training Experimental Treatment 4 Interventions

Standard Medical Care plus Resistance Training will continue to receive their regular standard clinical care during the 6-month intervention period of this study and will also receive supervised resistance exercise in addition to brief contacts from the research staff at weeks 6, 12, and 18.

Group II: Standard Medical Care plus Aerobic Training Experimental Treatment 4 Interventions

Standard Medical Care plus Aerobic Training will continue to receive their regular standard clinical care during the 6-month intervention period of this study and will also receive supervised aerobic exercise in addition to brief contacts from the research staff at weeks 6, 12, and 18.

Group III: Standard Medical Care Active Control 3 Interventions

Standard Medical Care will continue to receive their regular standard clinical care during the 6-month intervention period of this study and will also receive brief contacts from the research staff at weeks 6, 12, and 18.

Standard Medical Care is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Ozempic for:

• Type 2 diabetes
• Reducing the risk of major adverse cardiovascular events

Approved in United States as Wegovy for:

• Chronic weight management in adults with obesity or overweight

Approved in United States as Rybelsus for:

• Type 2 diabetes

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Reducing the risk of major adverse cardiovascular events

Approved in European Union as Wegovy for:

• Chronic weight management in adults with obesity or overweight

Approved in European Union as Rybelsus for:

• Type 2 diabetes

Approved in Canada as Ozempic for:

• Type 2 diabetes

Approved in Canada as Wegovy for:

• Chronic weight management in adults with obesity or overweight

Approved in Canada as Rybelsus for:

• Type 2 diabetes

Approved in Japan as Ozempic for:

• Type 2 diabetes

Approved in Japan as Wegovy for:

• Chronic weight management in adults with obesity or overweight

Approved in Japan as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Published Research Related to This Trial

Obesity rates have more than doubled globally since 1980, leading to increased prevalence of related diseases such as diabetes and heart disease, highlighting the urgent need for effective obesity treatments.

Currently, orlistat is the only anti-obesity drug approved in Europe, while other previously used medications like sibutramine have been removed from the market due to safety concerns, emphasizing the challenges in developing safe and effective obesity therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targets for medical therapy in obesity. Baretić, M.[2012]

Obesity medications are categorized into four groups: antidepressants, stimulants, fat blockers, and diabetes medications, each with unique effects and side effects, but only lorcaserin and orlistat are approved for long-term use.

High costs and the classification of many obesity medications as controlled substances limit access for underserved populations, and there are currently no approved options for pregnant or lactating women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Past, Present, and Future of Pharmacologic Therapy in Obesity. Rodríguez, JE., Campbell, KM.[2016]

In a study of nearly 17,000 orlistat users and 3,500 sibutramine users, the long-term persistence rates for these antiobesity medications were extremely low, with only 2% of patients continuing therapy after 2 years.

This analysis revealed that the discontinuation rates for orlistat and sibutramine were significantly higher in a real-world setting compared to previous clinical trials, where average weight loss was less than 5 kg and adverse effects were common.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term persistence with orlistat and sibutramine in a population-based cohort. Padwal, R., Kezouh, A., Levine, M., et al.[2018]

There are three main drugs approved for long-term obesity treatment: orlistat (5-8 kg weight loss but with gastrointestinal side effects), lorcaserin (4-7 kg weight loss with few side effects), and a combination of phentermine and topiramate (8-10 kg weight loss, but requires pregnancy verification).

For patients with chronic diseases like diabetes or depression, it's important to choose medications that not only treat the condition but also promote weight loss, as some drugs can cause weight gain or have a neutral effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on obesity pharmacotherapy. Bray, GA., Ryan, DH.[2014]

A total of 4941 adverse event (AE) reports were identified for antiobesity medicines in Europe from 2007 to 2014, with over 90% classified as serious, including 159 deaths, highlighting significant safety concerns associated with these medications.

The most commonly reported serious AEs were cardiac (19%) and psychiatric disorders (18%), particularly linked to orlistat and rimonabant, indicating a need for ongoing safety monitoring despite the withdrawal of some products from the market.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse events reported for antiobesity medicines: postmarketing experiences from the EU adverse event reporting system EudraVigilance. Aagaard, L., Hallgreen, CE., Hansen, EH.[2018]

Newly approved antiobesity drugs like lorcaserin and the phentermine/topiramate combination have shown significant weight loss and improvements in cardiometabolic health risks.

While adverse events from these medications are rare and often decrease over time, specific safety concerns must be addressed, highlighting the need for well-trained healthcare providers in obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of new antiobesity drugs. Hainer, V.[2018]

Patients starting anti-obesity drugs had a higher prevalence of cardiovascular and psychiatric co-morbidities compared to those not prescribed these drugs, indicating a baseline risk that could lead to increased adverse effects during treatment.

A significant number of patients (77.7%) discontinued anti-obesity drugs within 90 days, which may limit the potential cardiovascular benefits associated with weight loss from these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular and psychiatric risk profile and patterns of use in patients starting anti-obesity drugs. Willemen, MJ., Mantel-Teeuwisse, AK., Straus, SM., et al.[2009]

Pharmacotherapy for obesity can be considered for individuals with a BMI of 30 or greater, or 27 or greater with weight-related health issues, highlighting the importance of medication in weight management when lifestyle changes alone are insufficient.

The effectiveness of antiobesity medications, such as phentermine and liraglutide, relies on customizing treatment to individual patient behaviors and health conditions, along with careful monitoring of their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity Pharmacotherapy. Saunders, KH., Umashanker, D., Igel, LI., et al.[2022]

A study involving over 28,000 patients found that orlistat and sibutramine have different safety profiles, with orlistat primarily causing gastrointestinal issues like diarrhea, while sibutramine was associated with central nervous system effects and hypertension.

The findings from prescription-event monitoring (PEM) were consistent with published case reports, confirming that the adverse events linked to these medications align with their distinct mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profiles of orlistat and sibutramine: results of prescription-event monitoring studies in England. Perrio, MJ., Wilton, LV., Shakir, SA.[2021]

Weight management interventions should start before metabolic syndrome develops, emphasizing the importance of early lifestyle changes like diet and exercise for overweight and obese individuals.

For patients with a BMI over 30 or those with a BMI between 27 and 30 with additional risk factors who struggle with diet and exercise, pharmacotherapy options like sibutramine, orlistat, and phentermine are available and FDA-approved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of lifestyle changes treatment plans and drug therapy in controlling cardiovascular and metabolic risk factors. Pi-Sunyer, FX.[2018]

Anti-obesity drugs can be an effective part of a comprehensive weight management strategy for patients who have not achieved a 10% weight loss through diet and exercise alone after three months, highlighting the need for a multidisciplinary approach to obesity treatment.

Successful management of obesity requires regular monitoring and a structured program that includes clear weight-loss goals, documentation of health risks, and guidelines for drug use, ensuring that patients receive appropriate care and support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging management strategies for obesity. Kopelman, PG.[2014]

Losing just 5% of body weight can lead to significant health improvements, but many individuals struggle to maintain weight loss through diet and exercise alone, highlighting the need for additional treatment options.

As of 2012, two new medications, lorcaserin and phentermine/topiramate, have been approved for long-term obesity treatment, and bariatric surgery is recommended for patients with severe obesity (BMI ≥40 or ≥35 with comorbidities) as a more intensive intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. Kushner, RF., Apovian, CM., Fujioka, K.[2018]

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