Jump to: Why Mounjaro and sitagliptin aren’t typically used together | Potential risks of combining Mounjaro with sitagliptin | Transitioning from sitagliptin to Mounjaro | Frequently asked questions | Take home message
It’s generally not recommended to take Mounjaro (tirzepatide) with sitagliptin.
Combining Mounjaro with sitagliptin isn’t recommended due to their overlapping mechanisms and increased risk of side effects without proven additional benefits.
Both medications work on similar pathways to control blood sugar. Mounjaro is a GIP/GLP-1 receptor agonist, whereas sitagliptin is a DPP-4 inhibitor that increases the natural levels of GLP-1.
Using them together essentially doubles down on the same mechanism, which can increase the risk of hypoglycemia (low blood sugar) and digestive side effects without providing additional therapeutic benefits.
Major clinical trials of Mounjaro, including the SURPASS program, deliberately excluded patients taking DPP-4 inhibitors like sitagliptin. This means there’s no robust evidence supporting the safety or effectiveness of this combination, which is why healthcare providers typically recommend discontinuing sitagliptin when starting Mounjaro.
If you’re currently taking sitagliptin and your doctor recommends switching to Mounjaro, you should discuss a transition plan rather than assuming you’ll take both medications together.
In rare cases where a healthcare provider might consider this combination, it would require very close monitoring and should be considered exceptional rather than standard practice.
Why Mounjaro and sitagliptin aren’t typically used together
Mounjaro and sitagliptin target similar pathways in the body but work through different mechanisms.
Understanding how these medications work helps explain why combining them isn’t generally recommended.
How these medications work
Mounjaro (tirzepatide) is a dual-action medication that:
- Activates both GIP and GLP-1 receptors directly (by mimicking the GLP-1 and GIP hormones)
- Slows stomach emptying
- Reduces appetite by acting on the brain
- Enhances insulin release when blood sugar is high
- Reduces glucagon production (a hormone that raises blood sugar)
Sitagliptin (Januvia) works differently by:
- Inhibiting the DPP-4 enzyme that breaks down natural GLP-1
- Indirectly increasing GLP-1 levels in the body
- Enhancing insulin production when blood sugar rises
- Reducing glucagon secretion
While these approaches differ slightly, they ultimately achieve similar effects through the incretin system, which is why using both creates redundancy and increased risk without clear benefits.
Potential risks of combining Mounjaro with sitagliptin
Taking Mounjaro and sitagliptin together may lead to several concerns that healthcare providers consider when making treatment recommendations.
Increased side effect risk
The most significant concerns with this combination include:
- Heightened hypoglycemia risk – Both medications lower blood sugar through similar pathways, potentially causing dangerous drops in glucose levels
- Intensified digestive side effects – Nausea, vomiting, and diarrhoea could be more pronounced with both medications
- Potential pancreatic effects – Both drugs have separately been associated with rare cases of pancreatitis; the combination hasn’t been adequately studied
These concerns are particularly important if you’re also taking other medications that lower blood sugar, such as insulin or sulfonylureas.
Lack of proven additional benefit
Beyond the increased risk profile, there’s little evidence that taking both medications provides additional benefits over using Mounjaro alone:
- Clinical trials haven’t demonstrated superior glucose control with the combination
- The significant weight loss effects of Mounjaro appear sufficient without adding sitagliptin
- The overlapping mechanisms suggest little theoretical advantage to using both
This unfavourable risk-benefit profile is why healthcare providers typically discontinue sitagliptin when initiating Mounjaro therapy.
Transitioning from sitagliptin to Mounjaro
If you’re currently taking sitagliptin and your healthcare provider recommends starting Mounjaro, the typical approach is to discontinue sitagliptin rather than take both medications simultaneously.
Standard switching protocol
The most common approach involves:
- Complete discontinuation – Sitagliptin is usually stopped completely when starting Mounjaro
- Immediate transition – Unlike some medications that require tapering, sitagliptin can typically be stopped the day Mounjaro is started
- Starting at a low dose – Beginning with the lowest Mounjaro dose (2.5mg weekly) helps minimise side effects during transition
- Monitoring response – Close blood glucose monitoring during the first few weeks helps ensure adequate control during the transition
This approach aligns with how clinical trials evaluated Mounjaro and with current prescribing guidelines.
Special considerations for specific patients
In rare instances, healthcare providers might consider temporary overlap or other approaches for specific patient situations:
- Poorly controlled diabetes – Some clinicians might briefly overlap medications while Mounjaro reaches therapeutic levels
- History of difficult transitions – Patients who’ve struggled when changing medications previously may need more individualised approaches
- Complex medical histories – Those with multiple health conditions might require specialised transition plans
These exceptions should be explicitly discussed with your healthcare team and would require enhanced monitoring.
Frequently asked questions
Why can’t I take both medications if they work differently?
While the medications have different mechanisms (direct receptor activation vs. preventing natural GLP-1 breakdown), they ultimately affect the same pathways and receptors. This increases the risk of side effects without proven additional benefits.
I’ve been prescribed both medications, what should I do?
If you’ve been prescribed both Mounjaro and sitagliptin, you should contact your healthcare provider immediately for clarification.
In most cases, this would not be intentional, as standard practice is to discontinue sitagliptin when starting Mounjaro.
Will I lose blood sugar control if I stop sitagliptin and start Mounjaro?
Mounjaro is generally more potent than sitagliptin in controlling glucose levels. Clinical trials show that Mounjaro alone provides excellent glucose management and significant weight loss benefits.
Most patients maintain or improve blood sugar control when switching from sitagliptin to Mounjaro.
Are there any cases where taking both might be appropriate?
While there might be rare, exceptional cases where a healthcare provider might consider short-term overlap, this would be uncommon and require very close medical supervision. Current medical guidance does not support the routine use of combined medications.
How soon after stopping sitagliptin can I start Mounjaro?
Typically, you can start Mounjaro immediately after stopping sitagliptin. There’s no required waiting period between discontinuing one medication and starting the other.
Take home message
You should not take Mounjaro (tirzepatide) and sitagliptin together unless specifically directed by your healthcare provider in exceptional circumstances.
This combination isn’t advised due to overlapping mechanisms, increased side effect risks, and lack of proven additional benefits.
If you’re currently taking sitagliptin and are being considered for Mounjaro, the standard approach is to discontinue sitagliptin when starting Mounjaro rather than taking both medications simultaneously. This approach aligns with how clinical trials evaluated Mounjaro and with current prescribing guidelines.
Always discuss any changes to your medication with your healthcare provider to ensure they align with your specific health needs and treatment goals. Never stop or start medications without proper medical guidance.
Second Nature's Mounjaro programme
Second Nature provides Mounjaro as part of our Mounjaro weight-loss programme
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) 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.
