Understanding the Rise of High-Dose GLP-1 and Dual Agonists
What GLP-1 Agonists Do — and Why Dose Matters
GLP- 1 agonists act on GLP receptors that are found mainly in the gastrointestinal system as well as the brain and pancreas. They work by delaying gastric emptying, which means you are fuller for longer, they also work centrally in the brains appetite centres to suppress patients' appetite.
If you consider that these medications bind to the receptors in these locations and over time will lose effect as they get broken down naturally by the body. Higher doses firstly saturate the receptors to a higher degree, but on a simple level, there is also just more about.
The issue with all medication revolves around the potential for side effects i.e. if someone tolerates the medication, GI side effects are very common, and it takes time for patients to adapt to the new dietary intake as well as the body adapting to having the medication in the system.
This is why these medications have to be carefully titrated up at monthly intervals.
The Shift Toward Dual and Triple Agonists
The next generation of weight loss jabs are combining the effects of GLP –1 agonist alongside other peptides/systems which are involved in appetite regulation.
Tirzapetide combines GLP –1 agonist action alongside GIP agonist action. GIP stands for “gastric inhibitory polypeptide”. It is an incretin hormone that is secreted by the intestine in response to food, by mimicking the bodies natural version is enhances the action of the GLP 1 action, which is why Mounjaro statistically offers the highest percentage of weight loss.
In 2026/7 we will expect to see “triple agonists” such as Retatrutide. This drug is still not licensed, and we are yet to understand the full safety implications of the medication. But current research suggests it contains a GLP 1 and GIP agonist as well as a Glucagon agonist and has the potential to help patients to safely lose 20% body weight.
Wegovy 7.2 mg — The New High Bar for Semaglutide
Inside the STEP UP Clinical Program
The STEP UP trial was a randomised , double blind , placebo controlled and active controlled trial.
The simple aim was to see if the higher dose lead to significant enough benefit when compared to potential risks.
It was a big study which spanned across 95 hospitals in 11 countries.
Each of the 1407 participants were randomly assigned into a receiving 7.2mg Semaglutide, 2.4mg of Semaglutide or a Placebo.
The Coprimary endpoints were percentage reduction of 5% or greater of the 7.2mg vs the placebo group over 72 weeks.
Safety was assessed in all trial participants.
The findings suggested that 7.2mg retained a favourable risk benefit profile and that 7.2mg was superior to 2.4mg for body weight reduction in adults with obesity.
Of note the safety and tolerability were comparable between semaglutide 7·2 mg and 2·4 mg, except for the imbalance in dysaesthesia.
Key Findings from the Lancet 2025 Study
The key findings from the Lancet study in 2025 showed that patients could lose up to 20% or more weight and reduce their HBa1c (a marker for glucose exposure in the blood) and waist circumference.
Comparing 7.2 mg Wegovy vs Tirzepatide (Zepbound)
Mechanism Differences
- Contrast semaglutide’s GLP-1 only action vs tirzepatide’s dual GLP-1/GIP With the mechanism of action being different between the two drugs, it seems like the dual agonist action of Mounajro has been almost equalled by the high dose7.2mg Wegovy.
When looking at the 2 drugs 7.2mg Wegovy gives comparable percentage reduction in weight (~20% weight loss average (interim)) ,when compared directly to Mounjaro (~21% weight loss).
Efficacy Head-to-Head (Approximate)
It would need someone to conduct a head-to-head comparison study to fully assess both the benefits and the side effects/ risks.
We may never get that study, so in the interim as clinicians the decision between which is better will come down to a combination of clinical considerations, like if a patient has cardiovascular risk factors or diabetes, their past medical history and their BMI when starting, as well a patient factors such as preference and financial considerations
How Retatrutide and CagriSema Fit Into the Picture
Retatrutide — Triple Agonist Potential
- Overview of mechanism: GLP-1/GIP/glucagon triple receptor agonist.
- Early results: >24% mean weight loss (NEJM 2023).
- Anchor: [NEJM retatrutide phase 2 results].
CagriSema — Combining Cagrilintide + Semaglutide
- Explain combination of amylin analogue + semaglutide for synergistic appetite and satiety control.
- Phase 3b trials showed up to 20% weight loss for some patients with significantly more weight loss when compared to weight loss in all end points.
- Compare expected efficacy vs 7.2 mg semaglutide monotherapy.
Early indications suggest that there will be several new weight loss medications emerging in the next few years. However, with the research studies ongoing, it is still too early to make definitive conclusions on safety and how effective they may be.
The Future of GLP-1 Dose Escalation and Multi-Agonist Therapies
In the future it is possible that patients with Obesity will be managed much like a patient with high blood pressure is today. The drug choice and duration will be much more tailored to the individual. This choice will be better for patients who may currently find the options limited.
Key Takeaways
Summary: Comparing 7.2 mg Wegovy vs Other High-Dose GLP-1s / New Drugs
The blog explores the evolution of obesity treatments since Wegovy’s UK launch in 2023, highlighting the upcoming 7.2 mg dose of semaglutide as a major advancement. This higher dose promises greater weight loss—up to 20%—while maintaining a favorable safety profile, as shown in the STEP UP trial.
It explains how GLP-1 agonists work by delaying gastric emptying and suppressing appetite, and why dose escalation matters. The discussion then shifts to next-generation therapies like tirzepatide (Mounjaro), which combines GLP-1 and GIP agonism for superior efficacy (~21% weight loss), and future triple agonists like retatrutide, which may achieve >24% weight loss. CagriSema, a combination of semaglutide and an amylin analogue, also shows promise.
The blog compares Wegovy 7.2 mg with tirzepatide, noting similar efficacy but different mechanisms, and emphasizes that treatment choice will depend on patient-specific factors such as cardiovascular risk, diabetes, and cost. It concludes by forecasting a future where obesity management becomes highly personalized, akin to hypertension treatment, with multiple tailored drug options.
Key Takeaways:
- Wegovy 7.2 mg sets a new benchmark for semaglutide-based therapy.
- Dual and triple agonists represent the next frontier in weight-loss drugs.
- Safety and individualized treatment will remain central as the obesity drug pipeline expands.
Summary
Medications like semaglutide and tirzepatide, which belong to the GLP-1 class, offer powerful support for weight management when paired with proper dosing, consistent adherence, and a balanced lifestyle. Optimal outcomes are achieved through personalised clinical oversight, including adjustments to dosage and monitoring of diet and exercise.
Working closely with a PrivateDoc clinician allows your treatment plan to be customised to your specific needs, enhancing weight loss results while promoting long-term metabolic wellbeing.
