What are Mounjaro and Rybelsus?
Mounjaro and Rybelsus both belong to the GLP-1 receptor agonist class of medications, but they differ in how they’re taken, what they treat, and their effectiveness.
Mounjaro, made by Eli Lilly, contains the drug tirzepatide. It’s a weekly injection approved in the UK for type 2 diabetes and, following NICE guidance (TA1026), for weight management.3
Rybelsus, made by Novo Nordisk, contains oral semaglutide. It’s the only GLP-1 medication available as a tablet rather than an injection. It’s approved in the UK for type 2 diabetes only.4
Semaglutide is also available as an injection under the brand names Ozempic (for type 2 diabetes) and Wegovy (for weight management). Rybelsus delivers a lower dose of semaglutide than either injectable form.
How these medications work
Both medications mimic naturally occurring hormones that regulate hunger and blood sugar, but they differ in how they work and how they’re taken.
How Rybelsus works
Rybelsus mimics one hormone called GLP-1 (glucagon-like peptide-1), which:
- Slows food movement through your stomach, helping you feel fuller for longer
- Communicates with your brain’s appetite centre to reduce hunger
- Improves blood sugar control by enhancing insulin function
Because semaglutide is a protein, it would normally be destroyed by stomach acid. Rybelsus uses a special absorption enhancer called SNAC to protect the drug and allow a small amount to pass into the bloodstream.
Only about 1% of the oral dose is absorbed, which is why Rybelsus requires such specific dosing conditions.4
How Mounjaro works
Mounjaro activates two hormone receptors instead of one:
- Like Rybelsus, it activates the GLP-1 receptor
- It also activates GIP (glucose-dependent insulinotropic polypeptide), a second gut hormone involved in appetite regulation and blood sugar control
This dual-action mechanism likely explains why tirzepatide produces greater weight loss and improvements in blood sugar in clinical trials than GLP-1-only medications.1
Clinical evidence
There’s no published clinical trial directly comparing tirzepatide to oral semaglutide. However, we can draw useful conclusions from the trials that do exist.
SURPASS-2: tirzepatide vs injectable semaglutide in type 2 diabetes
The SURPASS-2 trial compared tirzepatide to injectable semaglutide 1 mg (the standard Ozempic dose) in 1,879 people with type 2 diabetes over 40 weeks.1
- Tirzepatide 15 mg: -11.2 kg average weight loss
- Injectable semaglutide 1 mg: -5.7 kg average weight loss
- HbA1c: -2.30% with tirzepatide 15 mg vs -1.86% with semaglutide 1 mg
Rybelsus 14 mg (the highest available oral dose) produces roughly equivalent blood levels to injectable semaglutide 0.5-1.0 mg per week, which is at or below the injectable dose tested in SURPASS-2.5
Put simply, tirzepatide outperformed a semaglutide dose that is equal to or higher than what Rybelsus can deliver.
The real-world gap between Mounjaro and Rybelsus is therefore likely to be at least as large as SURPASS-2 suggests.
Still, the MHRA is currently reviewing a 25 mg form of oral semaglutide, broadly described as “the wegovy pill”, for people living with obesity after it was approved in the U.S.
Results from the OASIS-4 trial suggest that 25 mg oral semaglutide supports an average weight loss of around 16.6%.
PIONEER 1: oral semaglutide for type 2 diabetes
The PIONEER 1 trial tested oral semaglutide as monotherapy in people with type 2 diabetes over 26 weeks.2
- Rybelsus 14 mg: -1.1% HbA1c reduction, -2.3 kg weight loss vs placebo
- These results confirm oral semaglutide is effective for blood sugar control, though the weight loss is modest compared to injectable options
| Outcome |
Mounjaro 15 mg (SURPASS-2)1 |
Rybelsus 14 mg (PIONEER 1)2 |
| HbA1c reduction |
-2.30% |
-1.1% |
| Weight loss |
-11.2 kg |
-2.3 kg (vs placebo) |
| Trial duration |
40 weeks |
26 weeks |
| Comparator |
Injectable semaglutide 1 mg |
Placebo |
These are different trials with different designs, so a direct comparison of the numbers is limited.
However, the overall picture is consistent: tirzepatide produces substantially greater weight loss and improvements in blood sugar than oral semaglutide.
Side effects and tolerability
Both medications share similar gastrointestinal side effects. Most are mild to moderate and improve as your body adjusts during dose escalation.
| Side effect |
Mounjaro (tirzepatide)6 |
Rybelsus (oral semaglutide)4 |
| Nausea |
12-18% (dose-dependent) |
~15% |
| Diarrhoea |
Common during titration |
~10% |
| Vomiting |
Common during titration |
~7% |
| Constipation |
6-17% (dose-dependent) |
Less common |
The gradual dose titration for both medications is designed to minimise these effects. Most side effects occur during the early weeks of treatment and reduce significantly over time.
Neither medication has shown significant safety concerns in clinical trials when prescribed and monitored appropriately. Both require regular follow-up with your prescriber.
Practical differences
The biggest practical difference between these two medications is how you take them: Mounjaro is a weekly injection, while Rybelsus is a daily tablet.
Injection vs tablet
Mounjaro uses a pre-filled pen that you inject once per week into your stomach, thigh, or upper arm. The needle is hidden, and the process takes about 10 seconds. Many people find it less uncomfortable than expected.
Rybelsus is a daily tablet, but it’s not as simple as swallowing a pill with breakfast. You must:4
- Take it first thing in the morning on an empty stomach
- Swallow it whole with up to half a glass of plain water (120 ml) only
- Wait at least 30 minutes before eating, drinking, or taking any other medication
- Never crush, split, or chew the tablet
These strict requirements exist because of the SNAC absorption enhancer. Any food, drink, or other medications in the stomach can significantly reduce the amount of semaglutide that is absorbed.
Dosing
Mounjaro starts at 2.5 mg weekly for four weeks, then increases to 5 mg. Your prescriber can increase your dose to 7.5 mg, 10 mg, 12.5 mg, or 15 mg based on your response.
Rybelsus starts at 3 mg daily for 30 days (a dose escalation phase, not therapeutic), then increases to 7 mg. If further improvement is needed, your prescriber may increase it to 14 mg.
Storage
- Mounjaro: Refrigerate (2-8°C) before first use; room temperature (below 30°C) for up to 21 days once in use
- Rybelsus: Store below 30°C. No refrigeration needed. Keep in the original blister pack to protect from moisture
Rybelsus has a practical storage advantage as no refrigeration is required at any point, making it more convenient for travel.
Cost and access in the UK
For type 2 diabetes
Both medications may be available through the NHS for type 2 diabetes under NICE guideline NG28, depending on your clinical profile and local formulary.
On private prescription, typical monthly costs are:
- Rybelsus: £85-210 per month, depending on dose and provider
- Mounjaro: £229-349 per month, depending on dose and provider
Rybelsus is generally less expensive than Mounjaro on private prescription.
For weight management
Rybelsus is not licensed for weight loss in the UK. If weight management is your primary goal, Mounjaro is the appropriate option. It received NICE approval for weight management (TA1026) in December 2024, with NHS access expanding through specialist weight management services.3
As previously mentioned, the MHRA is currently reviewing a 25 mg form of oral semaglutide, broadly described as “the wegovy pill”, for people living with obesity after it was approved in the U.S.
Results from the OASIS-4 trial suggest that 25 mg oral semaglutide supports an average weight loss of around 16.6%.
Who might prefer each option?
Individual responses vary, but certain factors may make one medication more suitable.
Mounjaro might suit you if:
- Weight loss is a primary goal — Mounjaro produces substantially greater weight loss in clinical trials and is licensed for weight management
- You want stronger blood sugar control — the dual function of the drug delivers greater HbA1c reductions than GLP-1-only medications
- You prefer a weekly routine — one injection per week with no dietary timing restrictions
- You want more dose flexibility — six dose levels allow finer adjustments
Rybelsus might suit you if:
- You have a strong aversion to injections — Rybelsus is the only oral GLP-1 option in the UK
- You have type 2 diabetes and want oral treatment — it’s an effective addition to oral diabetes management
- Storage convenience matters — no refrigeration required at any point
- Cost is a factor — Rybelsus is typically less expensive on private prescription
Frequently asked questions
Is Mounjaro more effective than Rybelsus?
Based on available evidence, yes. There’s no direct head-to-head trial, but Mounjaro outperformed injectable semaglutide (which delivers higher semaglutide levels than Rybelsus) in the SURPASS-2 trial.1 The gap between Mounjaro and Rybelsus for weight loss and blood sugar control is likely even larger.
Can I take Rybelsus for weight loss?
Rybelsus is only licensed for type 2 diabetes in the UK and should not be prescribed for weight loss alone.
The weight loss seen with Rybelsus in clinical trials is modest compared to injectable options. If weight loss is your primary goal, Mounjaro or Wegovy are the licensed options.
Is Rybelsus the same as Ozempic?
They contain the same active ingredient (semaglutide) but in different forms. Rybelsus is a daily tablet, Ozempic is a weekly injection.
Because oral semaglutide has very low bioavailability (about 1%), Rybelsus delivers less semaglutide to your bloodstream than Ozempic, despite the seemingly higher milligram dose on the label.4
Why does Rybelsus need to be taken on an empty stomach?
Rybelsus uses a special absorption enhancer (SNAC) that is only effective when taken on an empty stomach.
Any food, drink other than plain water, or other medications can interfere with absorption and significantly reduce how much semaglutide enters your bloodstream.4
Can I switch from Rybelsus to Mounjaro?
Yes. Many people switch to Mounjaro for greater weight loss or blood sugar control. Your prescriber will advise on the appropriate Mounjaro starting dose and timing based on your current Rybelsus dose. No washout period is needed between medications.
What happens if I eat within 30 minutes of taking Rybelsus?
Eating too soon after taking Rybelsus can significantly reduce the amount of semaglutide absorbed. This may make the medication less effective. If you consistently struggle with the 30-minute fasting requirement, discuss alternative options with your prescriber.
Are the side effects of Mounjaro worse than Rybelsus?
Both medications have similar gastrointestinal side effects. Nausea rates are broadly comparable: 12-18% for Mounjaro and around 15% for Rybelsus.46
Constipation may be more common with Mounjaro, while Rybelsus tends to cause more nausea at its higher dose. Side effects typically improve over time with both medications.
Is there an oral version of Mounjaro?
Not currently. Eli Lilly is developing an oral tirzepatide formulation, but this is still in clinical trials and not yet available. For now, Mounjaro is only available as a weekly injection.
Can I drink alcohol while taking Rybelsus or Mounjaro?
Moderate alcohol consumption is generally fine with both medications. Many people find that their tolerance decreases.
Both medications can cause nausea, and alcohol may worsen this, particularly during dose escalation.
How long do I need to take Rybelsus or Mounjaro?
Both are typically used long-term. For type 2 diabetes, treatment continues as long as it remains safe and effective. For weight management with Mounjaro, NICE recommends treatment for at least 12 months.3
Research shows that stopping medication without establishing sustainable lifestyle habits often leads to weight regain.
Take home message
Mounjaro is the more effective medication for both weight loss and blood sugar control based on available clinical evidence.
Its dual GIP/GLP-1 function produces substantially greater results than the GLP-1-only approach of Rybelsus.
Rybelsus has one clear advantage: it’s a tablet. For people who can’t tolerate injections or who strongly prefer oral medication, Rybelsus remains a reasonable option for managing type 2 diabetes. However, it’s not licensed for weight loss.
If weight management is your primary goal alongside diabetes treatment, Mounjaro offers both stronger clinical results and the appropriate UK licence.
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.
References
- Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515. https://www.nejm.org/doi/full/10.1056/NEJMoa2107519
- Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER 1: randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care. 2019;42(9):1724-1732. https://pubmed.ncbi.nlm.nih.gov/31186300/
- National Institute for Health and Care Excellence. Tirzepatide for managing overweight and obesity (TA1026). 2024. https://www.nice.org.uk/guidance/ta1026
- Electronic Medicines Compendium. Rybelsus 14 mg tablets – Summary of Product Characteristics. https://www.medicines.org.uk/emc/product/14389/smpc
- Overgaard RV, Navarria A, Hertz CL, Ingwersen SH. Clinical pharmacokinetics of oral semaglutide. Clin Pharmacokinet. 2024;63:603-618. https://pmc.ncbi.nlm.nih.gov/articles/PMC11215664/
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
