Semaglutide for Weight Loss in Obesity

(STEP UP Trial)

Recruiting at 182 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

1407 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new weight loss drug called semaglutide on overweight or obese individuals. The drug helps reduce hunger and increase fullness, promoting weight loss. Participants' progress will be monitored over a period of time. Semaglutide is a long-acting GLP-1 receptor agonist that has been shown to induce significant weight loss in individuals with obesity or overweight.

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 semaglutide safe for weight loss in humans?

Semaglutide has been shown to be generally safe in humans, with studies indicating it is well-tolerated and effective for weight loss and managing type 2 diabetes. It has been tested in various forms, including oral and injectable, and has demonstrated cardiovascular safety comparable to placebo in high-risk patients. ^{1 2 3 4 5}

How is the drug semaglutide unique for weight loss in obesity?

Semaglutide is unique because it is a once-weekly injection that has shown the largest weight loss of any obesity medication to date, with reductions of about 15% of initial weight over 68 weeks, and it also improves cardiovascular risk factors. ^{1 4 6 7 8}

What data supports the effectiveness of the drug Semaglutide for weight loss in obesity?

Research shows that Semaglutide, a drug used for type 2 diabetes, also helps with weight loss. In clinical trials, people taking Semaglutide lost more weight than those on other treatments, making it a promising option for managing obesity. ^{1 2 3 6 9}

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, 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]

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]

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 (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 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 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]

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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer? [2022]

2. Belgium pubmed.ncbi.nlm.nih.gov

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

3. Japan pubmed.ncbi.nlm.nih.gov

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

4. Belgium pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2023]

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

Semaglutide for the treatment of obesity. [2023]

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

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of overweight and obesity: A review. [2023]

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

Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. [2021]