CBD and sitagliptin (e.g. Januvia, Xelevia)
David ReichUpdated:Key points at a glance:
There are no direct clinical data on the combined use of CBD and sitagliptin. Sitagliptin is a DPP‑4 inhibitor, is primarily excreted unchanged via the kidneys and is only minimally metabolised via CYP3A4 and CYP2C8. It is also a P‑gp substrate. The potential for interactions via CYP enzymes with CBD is generally considered low, while possible effects involving transport proteins remain unclear. When introducing CBD, it may be advisable to start with a low dose, monitor blood sugar more frequently and seek medical advice, especially in the case of kidney conditions or additional diabetes medication.
At present, there are no direct clinical studies on CBD and sitagliptin (Januvia, Xelevia). Sitagliptin is a DPP‑4 inhibitor that is mostly excreted unchanged via the kidneys and only to a small extent metabolised via CYP3A4/CYP2C8; it is also a substrate of the transport protein P‑glycoprotein (P‑gp). This means the typical CYP interaction risk from CBD is likely to be lower than with many other prescription medicines. Effects via transporters such as P‑gp are theoretically possible, but their clinical relevance is unclear. If you are considering trying CBD while taking sitagliptin, start with a low amount, monitor your blood sugar more frequently and speak to your doctor beforehand – especially if you have kidney disease or take additional diabetes medication.
There are currently no direct studies on CBD and sitagliptin. As sitagliptin is primarily excreted via the kidneys, the typical CYP-enzyme interaction risk is considered relatively low. Nevertheless, it is advisable to monitor blood glucose levels and any unusual symptoms, and to seek medical advice—particularly if you have impaired kidney function or are taking additional diabetes medication.
More and more people are interested in the potential benefits of cannabidiol (CBD), a naturally occurring component of the hemp plant. It is often used as a supplement and is discussed in relation to everyday issues such as sleep and stress. Those who already take prescription medicines understandably ask themselves: does CBD fit with my treatment – for example, if I am taking sitagliptin?
What is sitagliptin (Januvia, Xelevia)? Mode of action and breakdown in the body
Sitagliptin is a dipeptidyl peptidase‑4 inhibitor (DPP‑4 inhibitor) used in the management of type 2 diabetes. It increases insulin release after meals and reduces glucagon secretion, which in turn influences blood sugar levels.
From a pharmacokinetic perspective, sitagliptin is largely excreted unchanged via the kidneys (around 79% renally). Only a small proportion is metabolised by liver enzymes (primarily CYP3A4 and, to a lesser extent, CYP2C8). Sitagliptin is also a substrate of the transport protein P‑glycoprotein (P‑gp), which transports active substances into and out of cells.
Because sitagliptin is mainly eliminated unchanged via the kidneys and only to a limited extent depends on CYP metabolism, the usual CYP‑related CBD drug interaction risk is lower than with many other medicines. Potential effects on transporters (e.g. P‑gp) and individual kidney function are more important for practical assessment.
How does CBD work in the body?
CBD interacts with the body’s endocannabinoid system (ECS), a complex network that is involved in processes such as sleep, mood, appetite and immune responses. CBD modulates various receptors and enzymes and is thought to influence inflammatory pathways and regulatory processes.
For potential interactions between CBD and prescription medicines, it is relevant that CBD can inhibit certain liver enzymes (CYP), particularly CYP3A4 and CYP2C19, and that at higher concentrations it may also affect transport proteins such as P‑gp. These enzyme and transporter effects can alter how some medicines are metabolised or transported in the body.
Read our article here about how CBD acts in the body
CBD may influence certain liver enzymes (CYP enzymes, particularly CYP3A4 and CYP2C19) as well as transport proteins such as P-glycoprotein (P-gp). These mechanisms are considered relevant when discussing potential interactions between CBD and prescription medicines, including sitagliptin.
How might CBD interact with sitagliptin?
CBD, CYP enzymes and sitagliptin
CBD mainly inhibits CYP3A4 and CYP2C19; there are also indications of effects on other enzymes depending on dose and formulation. However, sitagliptin is only minimally metabolised via CYP3A4/CYP2C8 and is therefore less prone to typical CYP‑mediated CBD interactions.
Current state of research: there are no clinical studies demonstrating a significant interaction between CBD and sitagliptin. Available evidence on CBD points to inhibition of CYP3A4/CYP2C19 and, at higher concentrations, to possible P‑gp effects; the clinical significance of this specifically for sitagliptin has not been established.
CBD, P‑glycoprotein and transporter effects
Sitagliptin is a P‑gp substrate. In vitro, effects of higher CBD concentrations on P‑gp have been described. It remains unclear whether this is clinically relevant at commonly used CBD amounts. If P‑gp‑mediated transport were affected, this could theoretically alter sitagliptin levels, but this has not been confirmed in clinical studies.
Why kidney function matters with CBD and sitagliptin
Because sitagliptin is predominantly excreted unchanged via the kidneys, impaired kidney function can lead to higher sitagliptin levels. CBD itself is mainly metabolised in the liver; direct effects on kidney function have not been clearly demonstrated.
If kidney function is reduced (for example, a low eGFR), dose adjustments for sitagliptin are recommended – regardless of CBD use. In this situation, new supplements such as CBD should only be started after medical advice, with close blood sugar monitoring.
With sitagliptin, classic CYP-related interactions with CBD are considered unlikely. More relevant factors are kidney function and potential, theoretical effects on transport proteins such as P-gp. If kidney function is impaired or higher doses of CBD are used, blood glucose levels and any symptoms should be monitored particularly carefully, and medical advice should be sought.
| Active substance | Breakdown/transport | Relevant mechanisms | Possible consequence | Practical note |
|---|---|---|---|---|
| Sitagliptin | ~79% unchanged renal; minor CYP3A4/CYP2C8; P‑gp substrate | Kidney function, P‑gp | Higher levels possible in reduced kidney function | Know your kidney values; when starting CBD, monitor blood sugar closely |
| CBD | Hepatic (mainly CYP3A4/2C19); at high doses possible influence on P‑gp | CYP inhibition, transporter effects | Theoretically altered active substance levels | “Start low, go slow”; record symptoms and measurements |
| Mechanism | Relevance for sitagliptin | What you should bear in mind |
|---|---|---|
| CYP3A4/CYP2C8 | Rather low | CYP inhibition by CBD is known, but is likely to play a smaller role for sitagliptin |
| P‑glycoprotein (P‑gp) | Unclear/moderate (theoretical) | With higher CBD amounts, pay attention to symptoms and blood sugar |
| Renal excretion | High | If kidney function is impaired, only start after consulting your doctor |
Read our article here about interactions with CBD
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Practical tips if you take sitagliptin and are considering CBD
Cautious step‑by‑step approach
- Start with a low CBD amount and increase gradually (“start low, go slow”).
- Monitor blood sugar more closely – especially in the first 2–4 weeks after starting CBD or changing the amount.
- Watch for symptoms such as dizziness, unusual tiredness, palpitations, gastrointestinal discomfort, or conspicuous blood sugar readings.
- Be particularly cautious if you have kidney disease, are on additional treatment with insulin/sulfonylureas, or take multiple medicines – discuss CBD with a doctor beforehand.
- Do not rely on timing alone: taking products at different times of day (e.g. morning/evening) does not reliably reduce CYP or transporter effects and does not guarantee protection from CBD drug interactions.
- Pay attention to product quality: prefer products with a COA (certificate of analysis), clear batch identification and transparent manufacturing information. View all products
What and how often should you measure?
- Before starting CBD, record baseline values (e.g. fasting glucose) for 3–7 days.
- In the first 2–4 weeks: check fasting and, if needed, post‑meal values more frequently (e.g. 3–5 times per week).
- Keep a brief log: date, CBD amount, readings, notable events/symptoms.
If you are taking sitagliptin and are considering trying CBD, it is advisable to start with a low CBD dose and to check your blood glucose levels more frequently during the first few weeks, noting any unusual changes. If you have pre-existing conditions—particularly related to kidney function—or are taking additional diabetes medication, this should only be done after consulting a healthcare professional.
Side effects at a glance – to consider individually and in combination
CBD
CBD is generally considered well tolerated. Commonly reported effects include drowsiness, dry mouth, dizziness and gastrointestinal issues (e.g. nausea, diarrhoea). Changes in appetite can affect food intake and in turn influence blood sugar. If you have a sensitive stomach, consider taking CBD with a light meal and adjusting the amount slowly.
Sitagliptin
Sitagliptin is generally regarded as well tolerated. Mild gastrointestinal symptoms or headaches are relatively common. Low blood sugar (hypoglycaemia) is uncommon with sitagliptin alone, but more likely when combined with insulin or sulfonylureas.
In rare cases, pancreatitis may occur. Warning signs include severe, persistent abdominal pain (often radiating like a band to the back), nausea and vomiting – in such cases, seek medical assessment promptly.
When you should seek medical advice
- Persistent severe abdominal pain, possibly with nausea/vomiting (possible pancreatitis)
- Very low or unusually high blood sugar values despite your usual diet/medication
- Yellowing of the skin/eyes, dark urine, intense itching (possible liver involvement)
- New swelling, rapid weight gain or increasing shortness of breath
If you experience severe or unusual symptoms—such as persistent abdominal pain, markedly altered blood glucose levels, yellowing of the skin or eyes, shortness of breath, or sudden swelling—you should seek medical assessment promptly, regardless of whether CBD or sitagliptin is involved.
Conclusion: CBD and sitagliptin at a glance
There are currently no robust clinical interaction data for the combination of CBD and sitagliptin (Januvia, Xelevia). Due to the pharmacokinetics of sitagliptin (low dependence on CYP, predominantly renal excretion), the risk of typical CYP‑mediated CBD drug interactions is likely to be lower; transporter‑related effects (P‑gp) remain theoretical and their significance is unclear.
Anyone who still wishes to try CBD alongside sitagliptin should start with a low amount, monitor blood sugar closely during the first few weeks and seek medical advice beforehand if there is pre‑existing kidney disease, additional antidiabetic therapy or use of multiple medicines.
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Disclaimer: This article is for information purposes only and does not replace medical advice. Do not change medicines or dosages without consulting your doctor. No claims are made regarding the treatment or cure of illnesses.