Phentermine-Topiramate + Lifestyle Intervention for Obesity

Overseen By Lisa L Morselli, MD PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Disqualifiers: Diabetes, Hypertension, Heart disease, others

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

Compensation: Varies

Number of Visits: 8

Duration: 6 months

60 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have any of the listed conditions like diabetes, hypertension, or heart disease, you would not be eligible to participate.

What data supports the idea that the drug Phentermine-Topiramate + Lifestyle Intervention for Obesity is an effective treatment?

The available research shows that Phentermine-Topiramate, when combined with lifestyle changes like a reduced-calorie diet and increased physical activity, leads to significant weight loss. In clinical trials, more than 50% of participants lost at least 10% of their starting weight and maintained this loss for up to two years. This combination drug is more effective than using either phentermine or topiramate alone. Additionally, it has been shown to improve health-related quality of life and reduce risk factors for heart disease. Compared to other treatments, this drug offers a promising option for long-term weight management. ^{1 2 3 4 5}

What safety data exists for Phentermine-Topiramate treatment for obesity?

Phentermine-Topiramate (Qsymia) has been approved for obesity treatment in adults since 2012 and in pediatric patients aged 12 and older since 2022. Safety concerns include teratogenicity, increased heart rate, psychiatric and cognitive effects, and metabolic acidosis. Clinical trials have shown it to be effective for weight loss with a favorable adverse effect profile compared to monotherapy. However, longer-term cardiovascular safety data is still needed. ^{1 2 4 6 7}

Is the drug Phentermine-Topiramate a promising treatment for obesity?

Yes, Phentermine-Topiramate is a promising treatment for obesity. It helps reduce weight by decreasing appetite and increasing the feeling of fullness. Studies show it leads to significant weight loss when combined with diet and lifestyle changes. It has been approved for use in both adults and adolescents in the US. ^{2 4 6 8 9}

What is the purpose of this trial?

This study aims at identifying the neurohormonal biomarkers that characterize individuals at risk of greater metabolic adaptation to weight loss, a disproportionate decline in resting metabolic rate during and after weight loss.

Research Team

Lisa L Morselli, MD PhD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for individuals with a BMI of 30 or higher, from any ethnic background. It's not suitable for those with heart disease, active cancer, post-transplant patients, weight over 400 lbs., HIV/AIDS, pregnant or breastfeeding women, smokers, and people with liver or kidney disease, diabetes (type 1 or type 2), or hypertension.

Inclusion Criteria

BMI > or = 30 any ethnicity

Exclusion Criteria

I have diabetes.

I have liver disease.

I have heart disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are enrolled in a weight loss program based on lifestyle changes, including a 6-month subscription to a calorie-reduced meal replacement program with lifestyle coaching

6 months

Every 2 months (in-person)

Follow-up

Participants are monitored for changes in metabolic rate and hormone levels after weight loss

12 months

Every 6 months (in-person)

Treatment Details

Interventions

• Lifestyle Intervention with Meal Replacement Program
• Phentermine-Topiramate

Trial Overview The study tests if phentermine-topiramate combined with lifestyle changes affects metabolic adaptation after weight loss differently than just lifestyle changes and meal replacements. Researchers are looking at how the body adjusts its energy use during and after dieting.

Participant Groups

Group I: lifestyle intervention Experimental Treatment 1 Intervention

Participants will be enrolled in a weight loss program based on lifestyle changes. They will be given a 6-month subscription to a calorie-reduced meal replacement program that also offers lifestyle coaching.

Lifestyle Intervention with Meal Replacement Program is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Meal Replacement Program for:

• Weight Loss
• Obesity Management
• Metabolic Syndrome

Approved in European Union as Total Meal Replacement for:

• Weight Loss
• Obesity Management
• Type 2 Diabetes Management

Approved in Canada as Full Meal Replacement for:

• Weight Loss
• Obesity Management
• Metabolic Syndrome

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

The fixed drug combination of phentermine and extended-release topiramate (Qsymia™) is the first FDA-approved combination therapy for obesity in over two decades, showing significant potential for effective weight loss.

Clinical trials demonstrated that over 50% of participants achieved and maintained at least a 10% weight loss from baseline for up to 2 years, indicating robust efficacy for long-term obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine and topiramate for the management of obesity: a review. Cosentino, G., Conrad, AO., Uwaifo, GI.[2021]

Phentermine/topiramate (Qsymia®) is a combination medication approved in July 2022 for chronic weight management in pediatric patients aged 12 and older with obesity, specifically those with a BMI in the 95th percentile or greater.

This medication works by decreasing appetite and increasing feelings of fullness, and it is also being studied for other conditions like sleep apnea and type 2 diabetes in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine/Topiramate: Pediatric First Approval. Dhillon, S.[2022]

In two 56-week trials involving 751 and 1623 patients, phentermine/topiramate significantly improved health-related quality of life (HRQOL) in individuals with obesity, with improvements in both obesity-specific and physical HRQOL measures.

While weight loss (BMI reduction) was the primary factor driving these HRQOL improvements, reductions in depressive symptoms also played a significant role, indicating that both weight and mental health are important in enhancing quality of life for patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life in two randomized controlled trials of phentermine/topiramate for obesity: What mediates improvement? Kolotkin, RL., Gadde, KM., Peterson, CA., et al.[2019]

Qsymia™, a combination of phentermine and topiramate, has been shown to produce greater weight loss than either drug alone, making it an effective treatment for obesity since its approval in 2012.

While Qsymia™ is effective, it carries potential risks such as teratogenicity, increased heart rate, psychiatric and cognitive side effects, and metabolic acidosis, which are consistent with the known side effects of its individual components.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of phentermine/topiramate (Qsymia™) combination for the treatment of obesity. Shin, JH., Gadde, KM.[2021]

Phentermine-topiramate extended release (ER) has been shown to help obese individuals lose an average of 10% of their initial weight, which is about 8% more than a placebo, and it also reduces the risk of developing type 2 diabetes and improves cardiovascular disease risk factors.

While effective for weight loss, phentermine-topiramate ER can increase heart rate and poses risks for women of child-bearing age due to potential harm to infants, highlighting the need for careful monitoring and consideration in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination phentermine and topiramate extended release in the management of obesity. Alfaris, N., Minnick, AM., Hopkins, CM., et al.[2018]

In a 56-week phase 3 trial involving 2487 overweight or obese adults, the combination of phentermine and topiramate significantly reduced body weight compared to placebo, with participants losing an average of 8.1 kg and 10.2 kg for the lower and higher doses, respectively.

The treatment was effective in achieving at least 5% weight loss in 62% of participants on the lower dose and 70% on the higher dose, while common side effects included dry mouth and paraesthesia, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Gadde, KM., Allison, DB., Ryan, DH., et al.[2022]

The FDA has approved lorcaserin and the combination of phentermine and extended-release topiramate (phentermine/topiramate ER) for obesity treatment, expanding options beyond orlistat and supporting long-term weight management alongside lifestyle changes.

Phentermine/topiramate ER has been shown to result in greater weight loss compared to using phentermine or topiramate alone, and it may also improve cardiometabolic risk factors, although more long-term safety data is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate. Sweeting, AN., Tabet, E., Caterson, ID., et al.[2021]

In a 108-week study involving 676 overweight and obese participants with cardiometabolic disease, controlled-release phentermine/topiramate (PHEN/TPM CR) led to significant and sustained weight loss compared to placebo, with mean percentage changes in body weight of -9.3% and -10.5% for the lower and higher doses, respectively.

PHEN/TPM CR not only facilitated weight loss but also improved cardiovascular and metabolic health, showing a reduction in diabetes incidence, and was well tolerated over the study duration, with fewer adverse events reported in the second half of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Garvey, WT., Ryan, DH., Look, M., et al.[2023]

In a 12-week open-label trial with 10 participants suffering from binge-eating disorder (BED) and obesity, phentermine-topiramate significantly reduced weight, binge-eating episodes, and overall eating disorder severity.

The treatment was generally safe, with no serious adverse events reported, although dysgeusia (altered taste) was the most common side effect, suggesting that phentermine-topiramate may be a promising option for managing BED in overweight individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Phentermine-Topiramate Extended Release for the Treatment of Binge Eating Disorder: An Open-Label, Prospective Study. Guerdjikova, AI., Williams, S., Blom, TJ., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Phentermine and topiramate for the management of obesity: a review. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Phentermine/Topiramate: Pediatric First Approval. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Health-related quality of life in two randomized controlled trials of phentermine/topiramate for obesity: What mediates improvement? [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility of phentermine/topiramate (Qsymia™) combination for the treatment of obesity. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Combination phentermine and topiramate extended release in the management of obesity. [2018]

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

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate. [2021]

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

Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. [2023]

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

Combination Phentermine-Topiramate Extended Release for the Treatment of Binge Eating Disorder: An Open-Label, Prospective Study. [2020]