Can you take Mounjaro with metformin?

Jump to: What does the research say? | How do Mounjaro and metformin work together? | Is it safe to take both? | Who should consider this combination? | Side effects to watch for | Dosing and monitoring | Frequently asked questions | Take home message

Yes, you can take Mounjaro (tirzepatide) with metformin. This combination is one of the most effective treatment options for type 2 diabetes, with clinical trials showing it can reduce HbA1c by up to 2.3 percentage points and support weight loss of around 11-12 kg over 40 weeks.¹

The SURPASS-2 trial, published in the New England Journal of Medicine, specifically studied tirzepatide as an add-on to metformin in 1,879 people with type 2 diabetes.¹

The results showed that 92% of participants taking the highest dose of Mounjaro (15 mg) alongside metformin achieved an HbA1c below 7%, the target recommended by diabetes guidelines.

Notably, 51% of participants receiving the 15 mg dose achieved an HbA1c below 5.7%, which is considered the normal range for individuals without diabetes.¹

If your blood sugar isn’t well controlled on metformin alone, speak to your doctor about your treatment options and whether you’d be eligible for Mounjaro.

What does the research say?

The evidence for combining Mounjaro with metformin comes primarily from the SURPASS clinical trial programme, a series of large, well-designed studies involving thousands of participants.

SURPASS-2: The head-to-head trial

The SURPASS-2 trial is particularly relevant because it tested tirzepatide specifically in people already taking metformin (at least 1,500 mg daily).¹

Here’s what the 40-week results showed:

HbA1c reductions:

• Tirzepatide 5 mg: reduced HbA1c by 2.01 percentage points
• Tirzepatide 10 mg: reduced HbA1c by 2.24 percentage points
• Tirzepatide 15 mg: reduced HbA1c by 2.30 percentage points

Weight loss:

• Tirzepatide 5 mg: 7.6 kg (8.5% of body weight)
• Tirzepatide 10 mg: 9.3 kg (approximately 10% of body weight)
• Tirzepatide 15 mg: 11.2 kg (13.1% of body weight)

Achieving target HbA1c:

• 92% of participants on 15 mg achieved HbA1c below 7%
• 51% achieved HbA1c below 5.7% (normal, non-diabetic range)

These results were significantly better than semaglutide 1 mg (the comparison drug in the trial), where 81% achieved HbA1c below 7% and participants lost an average of 6.2 kg.¹

Long-term evidence from SURPASS-4

The SURPASS-4 trial followed participants for up to 104 weeks (2 years), providing reassurance about longer-term use.²

In participants taking tirzepatide with metformin alone (without sulfonylureas), the results at two years showed:

• HbA1c reductions of 2.3% to 2.6% depending on dose
• Very low rates of hypoglycaemia (0.9% to 3.6%)
• Sustained weight loss throughout the study period

How do Mounjaro and metformin work together?

Mounjaro and metformin act through different mechanisms, which is why they can complement each other to support lower blood sugar levels.

What metformin does

Metformin primarily works in our liver, where it reduces the amount of glucose our liver releases into our bloodstream. It also helps our muscles and tissues use insulin more effectively.

This is why metformin is particularly good at controlling fasting blood sugar levels: the readings we get first thing in the morning, before eating.

What Mounjaro does

Mounjaro (tirzepatide) is a dual GIP/GLP-1 receptor agonist, meaning it mimics 2 hormones that help regulate blood sugar and appetite.³

It works by:

1. Stimulating insulin release when blood sugar is high (glucose-dependent, so it doesn’t cause insulin release when blood sugar is normal)
2. Reducing glucagon secretion (glucagon is a hormone that raises blood sugar)
3. Slowing stomach emptying, which reduces blood sugar spikes after meals
4. Acting on appetite centres in the brain to reduce hunger

Why the combination works

When both medications are together, they’re addressing multiple aspects of blood sugar control:

• Metformin focuses on the glucose our liver produces (fasting blood sugar)
• Mounjaro focuses on the glucose spikes after meals and helps with weight loss
• Together, they improve insulin sensitivity in different ways

Significantly, because Mounjaro only stimulates insulin release when blood glucose is elevated, adding it to metformin doesn’t substantially increase the risk of hypoglycaemia (low blood glucose).²

Is it safe to take Mounjaro with metformin?

Yes, the combination of Mounjaro and metformin has been extensively studied and shown to be safe for most people with type 2 diabetes.

No significant drug interactions

There are no significant pharmacokinetic interactions between tirzepatide and metformin.³ This means neither medication affects how the other is absorbed or processed by your body.

Tirzepatide isn’t metabolised by the liver enzymes (CYP450 system) that process many other medications, which reduces the potential for drug interactions.

Low risk of hypoglycaemia

One of the most reassuring findings from clinical trials is the low risk of hypoglycaemia when Mounjaro is combined with metformin.²

In the SURPASS-4 trial, hypoglycaemia rates for participants on metformin alone were:

• Tirzepatide 5 mg: 2.0%
• Tirzepatide 10 mg: 0.9%
• Tirzepatide 15 mg: 3.6%

Compare this to 16.8% for participants taking insulin glargine with metformin.²

The risk increases significantly if you’re also taking sulfonylureas (like gliclazide) or insulin, so your doctor may need to reduce doses of these medications when starting Mounjaro.

Contraindications to be aware of

You should not take Mounjaro if you have:

• A personal or family history of medullary thyroid carcinoma
• Multiple endocrine neoplasia syndrome type 2 (MEN 2)
• A history of severe allergic reaction to tirzepatide
• Severe gastroparesis (delayed stomach emptying)

You should not take metformin if you have:

• Severe kidney impairment (eGFR below 30)
• Acute or chronic metabolic acidosis
• Diabetic ketoacidosis

Who should consider this combination?

The Mounjaro and metformin combination may be right for you if:

Your blood sugar isn’t controlled on metformin alone: If you’ve been taking metformin for at least 3 months and your HbA1c is still above your target, adding Mounjaro could help you reach your goals.

You need to lose weight and control blood sugar: Unlike metformin (which is weight-neutral) or insulin (which often causes weight gain), Mounjaro supports significant weight loss alongside blood sugar control.

You want to avoid hypoglycaemia: If you’re concerned about low blood sugar episodes, this combination has a very low hypoglycaemia risk compared to adding insulin or sulfonylureas.

You have cardiovascular risk factors: The weight loss and metabolic improvements observed with Mounjaro may benefit your cardiovascular health, although we’re still awaiting results from dedicated cardiovascular outcomes trials.

Who might not be suitable?

This combination may not be appropriate if you:

• Have a history of pancreatitis
• Have severe kidney disease (metformin contraindicated)
• Are pregnant, breastfeeding, or planning pregnancy
• Have a history of medullary thyroid cancer or MEN 2 syndrome
• Cannot tolerate gastrointestinal side effects

Side effects to watch for

When taking Mounjaro with metformin, you may experience side effects from either medication. Since both can affect your digestive system, gastrointestinal side effects may be more noticeable.

Common side effects from Mounjaro

The most frequently reported side effects in clinical trials were:¹

• Nausea (12-24% of participants)
• Diarrhoea (12-17%)
• Decreased appetite (6-12%)
• Vomiting (2-10%)
• Constipation
• Indigestion

These side effects are typically mild to moderate, occur most often during dose increases, and tend to improve over time as your body adjusts.

Common side effects of metformin

Metformin can also cause:

• Nausea
• Diarrhoea
• Stomach upset
• Metallic taste

Managing gastrointestinal side effects

Since both medications can affect your gut, here are some practical tips:

• Eat 3 main meals a day, with snack in between
• Base your meals on whole foods and minimise ultra-processed foods and take-aways
• Stay well hydrated, this is especially important to protect your kidneys
• Take metformin with food to reduce stomach upset
• Be patient as symptoms usually improve within the first few weeks

When to contact your doctor

Seek medical advice if you experience:

• Severe or persistent nausea and vomiting
• Signs of dehydration (dark urine, dizziness, dry mouth)
• Severe abdominal pain that could indicate pancreatitis
• Signs of an allergic reaction (rash, swelling, difficulty breathing)
• Symptoms of low blood sugar if taking other diabetes medications

Dosing and monitoring

How Mounjaro is dosed

Mounjaro is started at a low dose and gradually increased to minimise side effects:

• Starting dose: 2.5 mg once weekly for 4 weeks
• First increase: 5 mg once weekly
• Further increases: Can be increased by 2.5 mg every 4 weeks
• Maintenance doses: 5 mg, 10 mg, or 15 mg once weekly

Your doctor will determine the correct maintenance dose based on your blood sugar response and how well you tolerate the medication.

Metformin dosing

Most people taking Mounjaro with metformin will continue their current metformin dose. In the SURPASS trials, participants were taking at least 1,500 mg of metformin daily.¹

Your metformin dose typically doesn’t need to change when starting Mounjaro, unless you experience significant side effects.

Monitoring requirements

While taking this combination, your healthcare team should monitor:

• HbA1c: Every 3 months initially, then every 6 months once stable
• Blood glucose: Regular self-monitoring, especially during dose changes
• Kidney function: Regular eGFR tests (important for metformin dosing)
• Vitamin B12: Every 2-3 years on long-term metformin
• Weight: Regular monitoring to track progress
• Side effects: Especially gastrointestinal symptoms and signs of dehydration

Frequently asked questions

Can I take Mounjaro and metformin at the same time of day?

Yes, you can. Mounjaro is injected once a week and can be taken at any time of day, with or without food. Metformin is usually taken with meals to reduce stomach upset. There’s no need to separate the timing of these medications.

Will I need to stop metformin when starting Mounjaro?

No, in most cases you’ll continue taking metformin alongside Mounjaro. The combination has been well-studied and shown to be more effective than either medication alone.

How quickly will I see results?

Most people notice reduced appetite within the first few weeks of starting Mounjaro. Blood sugar improvements typically become measurable within 4-8 weeks, with HbA1c reductions continuing to improve over several months.

Is the combination more effective than Mounjaro alone?

The SURPASS trials suggest that adding Mounjaro to metformin produces positive results for blood sugar. Metformin provides a foundation of glucose control that complements Mounjaro’s effects, and continuing metformin is generally recommended unless there’s a specific reason to stop.

What if I experience too many side effects?

If gastrointestinal side effects are problematic, your doctor may slow down the dose titration of Mounjaro, giving your body more time to adjust. In some cases, temporarily reducing the metformin dose might help, though this isn’t usually necessary.

Can I drink alcohol while taking both medications?

It’s safe to drink alcohol in moderate levels on these medications, but be aware that alcohol can increase the risk of lactic acidosis with metformin and may affect blood sugar control. It’s best to discuss your alcohol intake with your doctor.

Will I need to take these medications forever?

This depends on your individual situation. Some people use Mounjaro to achieve significant weight loss and improved blood sugar control, then transition to lifestyle management with or without metformin. Others may need long-term medication support. Your healthcare team can help you plan for the future based on your progress and goals.

Is this combination available on the NHS?

Mounjaro (tirzepatide) was approved by NICE for type 2 diabetes in October 2023.⁴ NHS availability varies by area and typically requires that other treatments have been tried first. Private prescriptions are also available through regulated providers like Second Nature.

Take home message

Taking Mounjaro with metformin is not only safe but highly effective for managing type 2 diabetes. Clinical trials show this combination can reduce HbA1c by over 2 percentage points and support weight loss of 8-13% of body weight.

The low risk of hypoglycaemia makes this combination particularly attractive compared to adding insulin or sulfonylureas. Most side effects are gastrointestinal, tend to be mild to moderate, and improve over time.

If your blood sugar isn’t well controlled on metformin alone, or you’re looking to lose weight alongside improving your diabetes management, speak with your healthcare provider about whether adding Mounjaro might be appropriate for you.

References

1. Frías, J.P., et al. (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine, 385(6), 503-515.
2. Sharma, J., et al. (2025). Long-term efficacy and safety of tirzepatide in participants with type 2 diabetes with inadequate glycaemic control on metformin and/or sulfonylurea: Post-hoc analysis of SURPASS-4. Diabetes, Obesity and Metabolism.
3. Sanchez-Rangel, E. & Inzucchi, S.E. (2024). Tirzepatide. StatPearls Publishing.
4. National Institute for Health and Care Excellence. (2023). Tirzepatide for treating type 2 diabetes (TA924).