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

Trial Summary

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.

What data supports the effectiveness of the drug Ozempic for obesity?

Ozempic, along with other anti-obesity drugs like Wegovy and Rybelsus, is part of a group of medications that can help manage weight in patients with obesity. These drugs have been shown to produce significant weight loss and reduce health risks associated with obesity. ^{1 2 3 4 5}

What safety data exists for anti-obesity medications?

Anti-obesity medications have been linked to serious heart and mental health side effects, though these are rare and tend to decrease over time. It's important to consider specific safety concerns for each drug and consult healthcare providers knowledgeable in obesity management. ^{2 6 7 8 9}

How do the drugs Ozempic, Wegovy, and Rybelsus differ from other obesity drugs?

Ozempic, Wegovy, and Rybelsus are unique because they are based on semaglutide, a medication originally used for diabetes, which helps control appetite and blood sugar levels, leading to weight loss. Unlike some other obesity drugs, they are administered as injections (Ozempic and Wegovy) or oral tablets (Rybelsus), offering different options for patients. ^{1 2 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to learn about changes in body composition related to obesity medication use, and whether aerobic or resistance exercise training will impact these body composition changes. It will also provide information about whether aerobic or resistance exercise training has additional benefits on other health and fitness measurements. The main questions it aims to answer are: * Is there a difference in the change in body composition (fat mass, lean mass, muscle mass, and bone content) between the standard medical care and the exercise conditions (aerobic training and resistance training)? * Is there a difference in the change in body weight and BMI between the standard medical care and the exercise conditions (aerobic training and resistance training)? * Is there a difference in the change in cardiorespiratory fitness between the standard medical care and the exercise conditions (aerobic training and resistance training)? * Is there a difference in how much physical activity is completed between the standard medical care and the exercise conditions (aerobic training and resistance training)? * Is there a difference in the change in physical function between the standard medical care and the exercise conditions (aerobic training and resistance training)? * Is there a difference in the change in muscle strength between the standard medical care and the exercise conditions (aerobic training and resistance training)? * Is there a difference in the change in resting blood pressure between the standard medical care and the exercise conditions (aerobic training and resistance training)? * Is there a difference in the change in food intake between the standard medical care and the exercise conditions (aerobic training and resistance training)? * Is there a difference in the change in health-related quality of life between the standard medical care and the exercise conditions (aerobic training and resistance training)? Participants will: * Participate in an intervention for a period of 6 months that involves being assigned to a no exercise/standard medical care condition, or a supervised exercise condition (aerobic training or resistance training). * Visit the clinical before starting the study and at 6 months to complete study measurements of their body composition and other measurements to monitor their progress. * Complete a brief monitoring session at weeks 6, 12, and 18 across the 6 months. * Complete supervised exercise sessions at the research center 3x per week for 6 months (Participants in the exercise groups only: aerobic training or resistance training).

Research Team

Renee J. Rogers, Ph.D.

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Update on obesity pharmacotherapy. [2014]

2. England pubmed.ncbi.nlm.nih.gov

Overview of new antiobesity drugs. [2018]

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

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Emerging management strategies for obesity. [2014]

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

Use of lifestyle changes treatment plans and drug therapy in controlling cardiovascular and metabolic risk factors. [2018]

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

Serious adverse events reported for antiobesity medicines: postmarketing experiences from the EU adverse event reporting system EudraVigilance. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Cardiovascular and psychiatric risk profile and patterns of use in patients starting anti-obesity drugs. [2009]

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

The safety profiles of orlistat and sibutramine: results of prescription-event monitoring studies in England. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Long-term persistence with orlistat and sibutramine in a population-based cohort. [2018]

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

Obesity Pharmacotherapy. [2022]

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

Past, Present, and Future of Pharmacologic Therapy in Obesity. [2016]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Targets for medical therapy in obesity. [2012]