Semaglutide for Weight Loss in Obesity

(STEP UP Trial)

No longer recruiting at 201 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must not be taking: Glucose-lowering agents

Disqualifiers: Diabetes, High HbA1c, Thyroid cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 72 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how much weight participants can lose by taking semaglutide, a medication administered by injection, compared to a placebo ("dummy" treatment). Participants will receive either a high or low dose of semaglutide or the placebo, and researchers will compare their results. In addition to the medication, participants will receive guidance on healthy eating and staying active. This trial may suit adults with a BMI of 30 or more who have unsuccessfully tried to lose weight through diet. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new weight-loss treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on glucose-lowering medications, you must stop them at least 90 days before the screening.

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

Research has shown that semaglutide is generally safe for individuals aiming to lose weight. One study found that a 2.4 mg dose of semaglutide enabled significant weight loss safely, regardless of age, sex, or race. Another study compared semaglutide to a placebo and found it effective and safe when combined with healthier eating and increased exercise.

Some individuals might experience side effects, but these are usually mild. Common side effects include nausea and diarrhea, which often decrease over time. The FDA has already approved semaglutide for other uses, indicating a known safety profile. However, it is not recommended for pregnant individuals, as it may pose risks to the baby. Overall, semaglutide appears to be a promising and safe option for weight loss when used correctly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about semaglutide for weight loss in obesity because it offers a novel approach compared to traditional options like lifestyle changes, orlistat, and phentermine. Semaglutide is a GLP-1 receptor agonist, originally used for diabetes, but it also helps regulate appetite and food intake, leading to significant weight loss. Unlike other treatments that may require multiple doses per day, semaglutide is administered just once a week as a subcutaneous injection, making it more convenient. Additionally, the trial includes two dosage regimens—2.4 mg and 7.2 mg—allowing researchers to explore the most effective dose for weight loss outcomes.

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

This trial will evaluate the effectiveness of semaglutide for weight loss in individuals with obesity. Studies have shown that semaglutide can help people with obesity lose a significant amount of weight. In one study, participants taking semaglutide lost an average of 15% of their body weight over 68 weeks, while those taking a placebo lost only about 2.4%. Another study found that a 2.4 mg dose of semaglutide led to an average weight loss of 14.6 kg after one year. This treatment mimics a hormone in the body that helps control appetite, reducing hunger. These findings suggest that semaglutide can be an effective option for weight loss in individuals struggling with obesity. Participants in this trial will receive either a placebo or one of two doses of semaglutide (2.4 mg or 7.2 mg) to assess its impact on weight loss. ^{3 4 6 7}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for adults with obesity (BMI ≥ 30 kg/m²) who have tried and failed to lose weight through dieting. It's not open to people with a personal or family history of certain thyroid cancers, those treated with diabetes medications recently, or anyone whose weight changed by more than 11 pounds in the last 90 days.

Inclusion Criteria

Body mass index (BMI) greater than or equal to 30.0 kilogram per square meter (kg/m^2)

History of at least one self-reported unsuccessful dietary effort to lose body weight

I am either male or female.

Exclusion Criteria

I have a history of diabetes.

I have lost or gained more than 11 pounds in the last 3 months.

HbA1c greater than or equal to 48 millimoles per mole (mmol/mol) (6.5 percent) as measured by the central laboratory at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once-weekly injections of semaglutide or placebo, with dose escalation over 20 weeks followed by maintenance dosing for a total of 72 weeks

72 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Semaglutide

Trial Overview The study tests high doses of Semaglutide against a placebo ('dummy' medicine) and a lower dose of Semaglutide for weight loss. Participants will also receive guidance on healthy eating and exercise. Treatment allocation is random, with a higher chance of receiving Semaglutide.

How Is the Trial Designed?

Group I: Semaglutide 7.2 mg Experimental Treatment 1 Intervention

Participants will receive once-weekly injection of semaglutide subcutaneously (s.c.) in 20 week dose escalation period with dose escalation (0.25 milligram \[mg\], 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg, and 7.2 mg) every fourth week. Treatment was continued on the maintenance dose of 7.2 mg once-weekly for an additional 52 weeks until week 72.

Group II: Semaglutide 2.4 mg Experimental Treatment 1 Intervention

Participants will receive once-weekly s.c. injection of semaglutide in 20 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks until week 72.

Group III: Placebo Placebo Group 1 Intervention

Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks.

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

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

In the STEP clinical trial program, participants with obesity who received once-weekly semaglutide 2.4 mg experienced significant weight loss, averaging between 14.9% and 17.4% over 68 weeks, with 69%-79% achieving at least 10% weight loss compared to only 12%-27% with placebo.

Semaglutide 2.4 mg also led to improvements in cardiometabolic risk factors and had a consistent safety profile, primarily involving gastrointestinal side effects, indicating its potential as an effective treatment for obesity and related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of overweight and obesity: A review. Bergmann, NC., Davies, MJ., Lingvay, I., et al.[2023]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

High-dose once-weekly semaglutide has been shown to significantly reduce weight in patients with obesity or overweight, as demonstrated in four phase 3 clinical trials involving various populations, including those with diabetes.

While gastrointestinal side effects were common, semaglutide was generally well tolerated and also led to improvements in cardiometabolic risk factors, such as waist circumference and blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. Bradley, CL., McMillin, SM., Hwang, AY., et al.[2022]

Semaglutide, a GLP-1 receptor agonist with a long half-life, effectively promotes insulin secretion in a glucose-dependent manner, making it a valuable treatment for type 2 diabetes, approved for use worldwide and in Japan since 2018.

Oral semaglutide (Rybelsus®) is the first GLP-1 receptor agonist available in pill form, showing continuous benefits in glycemic control for patients with type 2 diabetes across various stages, as demonstrated in multiple global clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. Miyasaka, K.[2022]

Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to produce the largest weight loss of any obesity medication, with an average reduction of about 15% of initial body weight over 68 weeks.

In addition to significant weight loss, semaglutide also improves cardiovascular risk factors and physical functioning, making it a promising option for chronic weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. Chao, AM., Tronieri, JS., Amaro, A., et al.[2023]

In a phase 3 trial involving 667 adults with overweight or obesity, oral semaglutide 50 mg taken daily resulted in a significant average weight loss of 15.1% compared to only 2.4% with placebo over 68 weeks, demonstrating its efficacy in weight management.

While semaglutide was effective, it was associated with a higher incidence of adverse events, particularly gastrointestinal issues, affecting 80% of participants, indicating that while it is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Knop, FK., Aroda, VR., do Vale, RD., et al.[2023]

Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has been shown to achieve significant and sustained weight loss in individuals with obesity, surpassing results from previous weight-loss medications, and has been approved for use alongside diet and exercise.

Emerging treatments like tirzepatide and cagrilintide are demonstrating even greater weight loss effects than semaglutide, indicating a shift towards more effective 'weight-centric' strategies for managing obesity and related conditions like type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer? Colin, IM., Gérard, KM.[2022]

Citations

1. vox.com vox.com/future-perfect/467025/ozempic-glp-1-drugs-obesity-weight-loss

The Ozempic effect is finally showing up in obesity data - Vox ... Ozempic — produced about 15 percent average weight loss over 68 weeks when paired with basic lifestyle support. Other combinations have ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40875186/

Real-World Weight Loss Observed With Semaglutide and ... After 1 year of follow-up, the mean weight loss from baseline with semaglutide 2.4 mg and tirzepatide was - 14.6 and - 17.2 kg, respectively, ...

3. nature.com nature.com/articles/s41591-024-02996-7

Long-term weight loss effects of semaglutide in obesity ... In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2032183

Once-Weekly Semaglutide in Adults with Overweight or ... Results. The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo ...

5. fda.gov fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss

FDA's Concerns with Unapproved GLP-1 Drugs Used for ... FDA has warned companies that have illegally sold unapproved drugs containing semaglutide, tirzepatide or retatrutide that are falsely labeled “for research ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603723/

Semaglutide - StatPearls - NCBI Bookshelf In addition, the weight loss effects of semaglutide are not deemed beneficial for pregnant individuals and may pose a risk of harm to the fetus.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38679221/

A Systematic Review and Meta-Analysis of Randomized ... At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared with 2.2% with placebo (RR 15.08, ...