Novo Nordisk’s Higher-Dose Wegovy Shows Up to 27.7% Weight Loss in STEP UP Trial Analysis

Novo Nordisk has unveiled new sub-analysis data from its large Phase 3 STEP UP clinical trial, showing that higher-dose Wegovy (semaglutide 7.2 mg) delivered substantial weight loss in people with obesity — regardless of how quickly they initially responded to treatment.

The findings were presented at the European Congress on Obesity held in Istanbul, Türkiye, and further strengthen Novo Nordisk’s position in the rapidly expanding obesity treatment market.

The new analyses also revealed that most of the weight lost with Wegovy came from body fat while muscle function and muscle health were largely preserved.

STEP UP Trial Evaluated Higher-Dose Wegovy

The STEP UP study evaluated:

• Semaglutide 7.2 mg
• Semaglutide 2.4 mg
• Placebo

The 72-week trial included more than 1,400 adults living with obesity without type 2 diabetes.

Key Weight Loss Results

Participants receiving:

• Semaglutide 7.2 mg
  • Lost an average of 21% of body weight
  • Equivalent to approximately 23 kg
• Semaglutide 2.4 mg
  • Lost around 17.5%
• Placebo
  • Lost only 2.4%

The safety and tolerability profile of the higher 7.2 mg dose remained broadly consistent with the currently approved 2.4 mg formulation.

Early Responders Achieved Nearly 28% Weight Loss

One of the most notable findings from the new sub-analysis involved “early responders.”

Who Were Considered Early Responders?

Patients who lost:

• 15% or more body weight within the first 24 weeks

were classified as early responders.

Early Response Rates

Among trial participants:

• 27% of people on semaglutide 7.2 mg were early responders
• 21% on semaglutide 2.4 mg qualified as early responders
• Only 3% of placebo participants achieved similar results

Long-Term Outcomes

Patients in the higher-dose early responder group achieved:

• 27.7% mean weight loss by week 72

The analysis also showed that participants receiving semaglutide 7.2 mg reached major weight-loss milestones faster than those on the 2.4 mg dose.

Weight Loss Primarily Came From Fat Reduction

A separate body composition sub-analysis involving MRI scans from 55 participants provided further insight into how semaglutide affected fat and muscle tissue.

Key Body Composition Findings

Researchers found that:

• 84% of total weight loss came from fat mass reduction
• Abdominal visceral fat decreased by more than 30%
• Muscle mass declined by only around 10% compared to baseline

Importantly, researchers reported improvements in muscle quality and muscle health despite the weight loss.

Muscle Function Was Preserved

One of the major concerns surrounding rapid weight loss therapies is the potential loss of muscle function. However, according to the STEP UP sub-analysis:

• Functional muscle strength remained stable
• Participants maintained performance in a:
  • 30-second sit-to-stand test
• Muscle function results were comparable between semaglutide and placebo groups

These findings suggest that semaglutide-driven weight loss may selectively target harmful fat stores while preserving functional strength.

Why Visceral Fat Reduction Matters?

Visceral fat, the fat stored around internal organs, is strongly associated with:

• Cardiovascular disease
• Type 2 diabetes
• Metabolic syndrome
• Inflammation
• Cardiometabolic complications

Reducing visceral fat by more than 30% could potentially offer significant long-term metabolic and cardiovascular benefits beyond weight reduction alone.

Expert Commentary Highlights

Dr. Dror Dicker of Tel-Aviv University emphasized that obesity is a chronic disease requiring long-term treatment strategies.

He noted that while early responders may achieve the greatest overall weight loss, patients who respond more gradually still experience clinically meaningful outcomes.

According to Dicker, these insights could help healthcare professionals:

• Set realistic treatment expectations
• Improve patient engagement
• Support long-term treatment adherence

Novo Nordisk Highlights Fat-Focused Weight Loss

Emil Kongshøj Larsen, Executive Vice President and Head of International Operations at Novo Nordisk, said the new findings reinforce the strong potential of higher-dose Wegovy.

He highlighted that people living with obesity often want therapies that specifically reduce fat while preserving muscle mass and physical function.

Regulatory Status of Wegovy

Wegovy continues to expand globally across multiple formulations.

Current Approvals

Wegovy Injection

The once-weekly injectable formulations:

• 2.4 mg
• 7.2 mg

have received approvals from:

• US FDA
• European Medicines Agency (EMA)
• Other global regulatory agencies

Wegovy Oral Pill

Novo Nordisk’s once-daily Wegovy pill (semaglutide 25 mg):

• Has been approved by the FDA
• Is currently under review by the EMA and other regulators

Obesity Drug Competition Continues to Intensify

The obesity treatment market has become one of the most competitive sectors in the pharmaceutical industry.

Drugmakers are increasingly competing on:

• Total weight loss achieved
• Speed of weight reduction
• Muscle preservation
• Long-term safety
• Convenience of administration

The STEP UP data positions higher-dose semaglutide as a potentially important option in the evolving obesity treatment landscape.

Final Thoughts

Novo Nordisk’s latest STEP UP analyses add further momentum to Wegovy’s growing clinical profile.

The findings suggest that higher-dose semaglutide may deliver:

• Significant and durable weight loss
• Faster achievement of treatment goals
• Major reductions in harmful fat mass
• Preservation of muscle function

As obesity therapies continue evolving beyond simple weight reduction toward broader metabolic health improvement, these results could play an important role in shaping future treatment strategies.