Evidence from clinical trials
Research comparing different semaglutide doses provides clear insights into how weight loss varies by dose.
The landmark STEP 1 trial studied 1,961 adults without diabetes taking Wegovy. Results showed:
| Semaglutide Dose |
Average Weight Loss (68 weeks) |
| 2.4mg (Wegovy) |
14.9% |
| Placebo |
2.4% |
However, this doesn’t tell the full story about lower doses. For that, we need to look at the different dosing phases and Ozempic trials. (Ozempic is the same drug as Wegovy, but available in lower doses.)
The SUSTAIN trials for Ozempic (semaglutide) in diabetes patients show the dose-response relationship more clearly:
| Semaglutide Dose |
Average Weight Loss (52 weeks) |
| 0.25 mg |
3-4% |
| 0.5 mg |
4-7% |
| 1 mg |
6-10% |
| 2.4 mg (Wegovy) |
9-15% |
A 2022 study published in Diabetes, Obesity and Metabolism directly compared multiple semaglutide doses and found that while each dose increase produced additional weight loss, the incremental benefit diminished at higher doses.
The largest improvements occurred when increasing from 0.25 mg to 0.5 mg and from 0.5 mg to 1 mg.
The jump from 1 mg to 2.4 mg added approximately 5-6% more weight loss for most participants.
Key points:
- Higher doses consistently produce greater average weight loss
- The relationship between dose and weight loss isn’t perfectly linear
- The biggest percentage improvement often occurs between 0.25 mg and 1 mg
- The 2.4 mg dose provides approximately 5-6% additional weight loss compared to 1 mg
Dose-response relationship
Understanding how your body responds to increasing doses of Wegovy helps set realistic expectations.
The science behind increasing doses
Semaglutide works by mimicking GLP-1, a hormone that regulates appetite and blood sugar.
Higher doses mean more of the active drug circulating in our bloodstream, leading to:
- A greater impact on lowering hunger
- Slower digestion
However, our body’s receptors can become partially saturated at certain doses, which explains why doubling the dose doesn’t necessarily double the weight loss effect.
Diminishing returns at higher doses
Research shows a pattern of diminishing returns as doses increase:
- The jump from 0.25 mg to 0.5 mg often produces a big decrease in hunger and appetite
- The increase from 0.5 mg to 1 mg typically yields significant additional benefits
- The step from 1 mg to 1.7mg shows more modest improvements
- The final increase to 2.4 mg adds benefit, but at a lesser rate than earlier increases
This relationship explains why some people maintain successfully on middle doses (like 1 mg) without needing to reach the maximum dose.
Key points:
- Higher doses lead to stronger effects on appetite and metabolism
- Benefits increase with each dose step, but at a decreasing rate
- Some people reach their personal ‘optimal dose’ before the maximum 2.4 mg
- The ideal dose balances maximum effectiveness with minimum side effects
Individual factors affecting results
Your personal response to Wegovy doses depends on multiple factors beyond the medication itself.
Genetic variation
Research has identified several genetic factors that influence GLP-1 response:
- Variations in the GLP-1 receptor gene can make some people more sensitive to even low doses
- Differences in metabolism genes affect how quickly semaglutide breaks down in your body
- Some people naturally produce more endogenous GLP-1, potentially affecting how they respond to external GLP-1 mimetics
Starting weight and BMI
Your baseline weight significantly impacts both absolute and percentage weight loss:
- People with higher starting weights often lose more total weight (in kg)
- Those with lower starting BMIs may see smaller absolute losses but similar percentage changes
- Starting BMI over 35 is associated with greater benefit from reaching maximum doses
Medication consistency
How consistently you take Wegovy matters more than the dose for many people:
- Missing doses can significantly reduce effectiveness regardless of dose
- Consistent weekly injections at a lower dose often outperform inconsistent use of higher doses
- The medication’s active duration means consistency supports stable blood levels
Activity level and diet quality
Your lifestyle significantly influences how well each dose works:
- Regular physical activity may improve weight loss outcomes in the long term while on Wegovy
- Higher protein intake will support more weight loss, whether you’re on GLP-1 medication or not
- Consuming a higher intake of ultra-processed foods can lead to overeating, even on GLP-1 medications
Key points:
- Individual genetic factors cause significant variation in dose response
- Your starting weight and body composition affect your results at each dose
- Consistency in taking the medication matters more than the dose for many people
- Lifestyle factors like diet quality and physical activity can enhance or diminish dose effectiveness
Side effects at different doses
Side effect frequency and intensity typically increase with higher doses of Wegovy, which may influence your optimal dose.
Common side effect patterns by dose
Research shows a clear correlation between dose and side effects:
| Dose |
Nausea Rate |
Vomiting Rate |
Diarrhoea Rate |
| 0.25 mg |
16-20% |
6-8% |
12-15% |
| 0.5 mg |
20-25% |
7-10% |
15-18% |
| 1 mg |
25-32% |
10-12% |
18-22% |
| 1.7 mg |
32-38% |
12-15% |
20-25% |
| 2.4 mg |
38-44% |
15-20% |
25-30% |
These figures from clinical trials indicate that side effects increase with dose, but the relationship isn’t strictly linear.
Many side effects also tend to improve over time at each dose level.
Tolerability considerations
Individual tolerability varies widely:
- Some people experience minimal side effects even at the highest dose
- Others find lower doses more manageable for long-term use
- Side effects may impact quality of life, work performance, and medication adherence
Balancing benefits and side effects
When determining your optimal dose, consider:
- Whether additional weight loss at higher doses outweighs increased side effects
- If side effects interfere with your daily activities or quality of life
- How long side effects persist after dose increases (typically 2-4 weeks)
Many patients and healthcare providers find that an individualised ‘sweet spot’ dose balances maximum weight loss with acceptable side effects.
Key points:
- Side effect frequency and intensity generally increase with higher doses
- Individual tolerability varies significantly
- Most side effects improve within 2-4 weeks at each dose level
- Finding your optimal dose often means balancing efficacy with side effect burden
How to find your ideal Wegovy dose
Making an informed decision about your Wegovy dose involves multiple considerations beyond just weight loss potential.
When higher doses make the most sense
Pushing to higher doses may be particularly beneficial if:
- Your BMI is over 35, where maximum weight loss provides greater health benefits
- You’ve had minimal side effects during titration
- You’re experiencing a weight loss plateau at lower doses
- You have significant weight-related health conditions requiring rapid improvement
- Cost is not a major concern
When remaining at lower doses might be preferable
Staying at lower doses (0.5 mg-1 mg) might be appropriate if:
- You’re losing weight at a sustainable rate of 1-2 lbs per week
- Side effects are significantly impacting your quality of life
- You’re approaching your target weight
- Cost is a concern
- You’re planning for long-term maintenance
NHS prescribing context
Current NHS guidelines typically recommend titrating to the maximum tolerated dose up to 2.4 mg.
However, maintenance at lower doses is becoming more accepted when:
- The patient is achieving good results
- Higher doses cause problematic side effects
- The patient’s weight-related health markers are improving
- The patient has developed sustainable lifestyle habits
Always discuss dose decisions with your healthcare provider, who can help evaluate your individual circumstances.
Key points:
- Higher doses make most sense for higher BMIs and minimal side effects
- Lower maintenance doses may be appropriate when you’re already seeing good results
- NHS guidance is evolving to support personalised dose optimisation
Frequently asked questions
Will I stop losing weight if I don’t increase my dose?
No, most people continue to lose weight even when they remain at lower doses, such as 0.5 mg or 1 mg.
While the rate of weight loss might be slower compared to higher doses, many achieve their goals without reaching 2.4 mg.
The key factors are consistency with the medication and maintaining healthy lifestyle habits.
Can I start at a higher dose to lose weight faster?
Starting at higher doses isn’t recommended. The gradual titration schedule (starting at 0.25 mg and increasing every 4 weeks) is designed to minimise side effects and allow your body to adjust.
Research shows that patients who follow the proper titration schedule are more likely to stay on the medication long-term and achieve better overall results.
What happens if I go back to a lower dose after being on the highest dose?
Some people do successfully decrease their dose after reaching 2.4 mg, especially for long-term maintenance.
You might experience a slight increase in hunger initially, but many find that a lower maintenance dose (like 1 mg) can sustain their weight loss if they’ve established healthy habits. Always make dose changes under medical supervision.
Do side effects always get worse at higher doses?
While side effects generally increase with higher doses, the relationship isn’t the same for everyone.
Some people experience minimal additional side effects at higher doses, while others find them more challenging.
Most side effects improve within 2-4 weeks at each dose level as your body adapts.
How do I know if I’m at my optimal dose?
Your optimal dose is the one that provides meaningful weight loss with manageable side effects. Signs you’re at your optimal dose include:
- Steady weight loss (1-2 lbs / 0.5-1 kg per week)
- Side effects that don’t significantly impact your quality of life
- Reduced hunger and food cravings
- Ability to maintain healthy eating patterns
This may or may not be the maximum 2.4 mg dose.
Can I take a lower dose of Wegovy for maintenance after reaching my goal weight?
Yes, many healthcare providers now support using lower maintenance doses (0.5-1 mg) after reaching your goal weight.
Research suggests that continued treatment at lower doses can help maintain weight loss, especially when combined with established healthy habits. This approach may also reduce side effects and costs during the maintenance phase.
Take home message
The higher doses of Wegovy typically lead to greater weight loss, with approximately 5-6% additional weight loss when increasing from 1 mg to 2.4 mg doses.
However, the relationship isn’t perfectly linear, and many people achieve significant results at lower doses.
Your optimal dose depends on multiple factors, including your starting weight, side effect tolerance, genetics, and cost.
While the 2.4 mg dose produces the largest average weight loss in clinical trials, the difference between middle and maximum doses is smaller than the difference between starting and middle doses.
Working with your healthcare provider to find your personal ‘sweet spot’ dose, one that balances effectiveness with side effects and cost, is the most sustainable approach.
For many people, this optimal dose may be lower than the maximum 2.4 mg, especially when combined with healthy eating habits and regular physical activity.
Remember that consistency with your medication schedule and lifestyle changes often matters more than reaching the highest possible dose.
The best dose is ultimately the one that helps you achieve your health goals while maintaining a good quality of life.
Second Nature's Mounjaro and Wegovy programmes
Second Nature provides Mounjaro or Wegovy as part of our Mounjaro and Wegovy weight-loss programmes.
Why choose Second Nature over other medication providers, assuming you're eligible?
Because peace of mind matters.
We've had the privilege of working with the NHS for over eight years, helping people across the UK take meaningful steps toward a healthier, happier life.
Our programmes are designed to meet people where they are, whether that means support with weight loss through compassionate one-to-one health coaching, or access to the latest weight-loss medications (like Mounjaro and Wegovy) delivered alongside expert care from a multidisciplinary team of doctors, psychologists, dietitians, and personal trainers.
At the heart of everything we do is a simple belief: real, lasting change comes from building better habits, not relying on quick fixes. We're here to support that change every step of the way.
With over a decade of experience, thousands of lives changed, and a long-standing record of delivering programmes used by the NHS, we believe we're the UK's most trusted weight-loss programme.
We hope to offer you something invaluable: peace of mind, and the support you need to take that first step.
