Can Rybelsus and Jardiance be taken together? Yes, these two diabetes medications can be safely combined when clinically appropriate for adults with type 2 diabetes. Rybelsus (semaglutide) is a GLP-1 receptor agonist that enhances insulin secretion and slows gastric emptying, whilst Jardiance (empagliflozin) is an SGLT2 inhibitor that increases urinary glucose excretion. Because they work through different mechanisms, they complement each other in improving blood glucose control. NICE guidance supports combination therapy when single medications fail to achieve target HbA1c levels. This article explains how these medications work together, safety considerations, dosing requirements, potential side effects, and when to seek medical advice.
Quick Answer: Rybelsus and Jardiance can be taken together safely for type 2 diabetes, as they work through different mechanisms to improve blood glucose control without significant drug interactions.
Yes, Rybelsus (semaglutide) and Jardiance (empagliflozin) can be taken together when clinically appropriate for adults with type 2 diabetes mellitus. Both medications work through different mechanisms to improve glycaemic control, making them complementary rather than conflicting therapies. There is no official contraindication to their concurrent use, and clinical evidence supports their combined efficacy in managing blood glucose levels.
Rybelsus belongs to the glucagon-like peptide-1 (GLP-1) receptor agonist class and works by enhancing insulin secretion in response to meals, suppressing glucagon release, and slowing gastric emptying. Jardiance is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that reduces blood glucose by increasing urinary glucose excretion, independent of insulin. Because these drugs target distinct pathways in glucose metabolism, they can work synergistically to achieve better diabetes control than either medication alone.
NICE guidance (NG28) on type 2 diabetes management supports the use of combination therapy when monotherapy fails to achieve target HbA1c levels. The combination of a GLP-1 receptor agonist and an SGLT2 inhibitor may be considered when HbA1c targets are unmet and/or in people with established or high risk of cardiovascular disease, heart failure or chronic kidney disease. Your GP or diabetes specialist will assess your individual circumstances, including your current HbA1c, body weight, cardiovascular risk profile, and renal function, before recommending this combination. It is essential that any changes to your diabetes medication regimen are made under medical supervision to ensure safety and optimal therapeutic benefit.
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Start HereThe safety profile of combining Rybelsus and Jardiance is generally favourable, with no significant pharmacokinetic or pharmacodynamic interactions between semaglutide and empagliflozin reported in clinical studies. Neither medication substantially affects the metabolism or elimination of the other, as they are processed through different pathways. Rybelsus is metabolised via proteolytic degradation (like endogenous peptides), whilst Jardiance undergoes glucuronidation primarily via UGT enzymes.
However, patients taking both medications should be aware of additive effects on blood glucose reduction. Whilst this is therapeutically desirable, it may increase the risk of hypoglycaemia, particularly if you are also taking insulin or a sulphonylurea (such as gliclazide). If you are on these additional glucose-lowering agents, your healthcare provider may need to adjust dosages to minimise hypoglycaemic risk. Both Rybelsus and Jardiance, when used without insulin or sulphonylureas, carry a low intrinsic risk of hypoglycaemia.
Cardiovascular and renal considerations are important when using this combination. Jardiance has shown reduction in cardiovascular mortality and heart failure hospitalisations in clinical trials. Injectable semaglutide has demonstrated cardiovascular benefits, though the evidence for oral semaglutide (Rybelsus) is more limited. From a renal perspective, Jardiance provides nephroprotective effects. For type 2 diabetes, empagliflozin should not be initiated if eGFR is below 60 mL/min/1.73m² and should be discontinued if eGFR persistently falls below 45 mL/min/1.73m². For heart failure or chronic kidney disease indications, empagliflozin 10 mg can be used down to an eGFR of 20 mL/min/1.73m². Your clinician will monitor renal function regularly to ensure safe continuation of therapy.
Importantly, SGLT2 inhibitors like Jardiance should be temporarily stopped during periods of acute illness, dehydration, or before major surgery to reduce the risk of diabetic ketoacidosis. If you feel unwell, particularly with vomiting or reduced fluid intake, contact your healthcare provider for advice about temporarily stopping Jardiance.
Rybelsus dosing typically begins at 3 mg once daily for 30 days, then increases to 7 mg daily. If additional glycaemic control is needed after at least 30 days on 7 mg, the dose may be increased to 14 mg once daily. Rybelsus must be taken on an empty stomach with no more than 120 mL of water, at least 30 minutes before the first food, drink, or other oral medications of the day. The tablet should be swallowed whole (not split, crushed or chewed). This specific administration requirement is crucial for optimal absorption, as food significantly reduces semaglutide bioavailability.
Jardiance dosing starts at 10 mg once daily for type 2 diabetes, which can be increased to 25 mg once daily if tolerated and additional glucose control is desired. For heart failure or chronic kidney disease indications, the dose is 10 mg once daily. Jardiance can be taken with or without food at any time of day, offering flexibility in administration. Many patients find it convenient to take Jardiance at a different time from Rybelsus to simplify their medication routine.
Practical administration strategy: A common approach is to take Rybelsus first thing in the morning on an empty stomach, wait the required 30 minutes, then have breakfast and take Jardiance with or after the meal. This ensures compliance with Rybelsus's strict absorption requirements whilst maintaining the convenience of once-daily dosing for both medications.
If you miss a dose of either medication, take it the next day as usual. Do not take a double dose to make up for a missed dose.
Your prescriber will individualise your dosing regimen based on several factors:
Current HbA1c and glucose control
Tolerability and side effects
Renal function (eGFR)
Cardiovascular risk profile
Body weight and weight loss goals
Concurrent medications
Dose adjustments should only be made under medical supervision. Never alter doses independently, as this may compromise glycaemic control or increase the risk of adverse effects.
Common side effects of Rybelsus include gastrointestinal symptoms—particularly nausea, vomiting, diarrhoea, abdominal pain, and decreased appetite. These effects are usually most pronounced during dose initiation and escalation, often improving over several weeks as your body adjusts. Taking Rybelsus with no more than 120 mL of water and waiting the full 30 minutes before eating may help minimise nausea.
Common side effects of Jardiance include genital and urinary tract infections (due to increased urinary glucose), increased urination (polyuria), and mild dehydration. Some patients experience postural dizziness, particularly when starting therapy. Rarely, SGLT2 inhibitors have been associated with diabetic ketoacidosis (DKA), even with near-normal blood glucose levels (euglycaemic DKA). Symptoms include nausea, vomiting, abdominal pain, unusual fatigue, and difficulty breathing. Very rarely, a serious infection called Fournier's gangrene can occur, causing severe pain, tenderness, redness, or swelling in the genital or perineal area, often with fever—this requires urgent medical attention.
When taking both medications together, you may experience side effects from either or both drugs. The gastrointestinal effects of Rybelsus combined with the diuretic effect of Jardiance may increase dehydration risk, particularly in hot weather or during illness. Maintain adequate fluid intake and be vigilant for signs of volume depletion.
Rapid improvement in blood glucose control with semaglutide may worsen diabetic retinopathy in some patients. Attend regular eye screening appointments and report any new visual symptoms promptly.
Essential monitoring requirements include:
HbA1c levels: Typically checked every 3–6 months to assess glycaemic control
Renal function: eGFR and serum creatinine monitored regularly (at least annually, more frequently if borderline)
Body weight: Both medications may promote weight loss
Blood pressure: Monitor for hypotension, especially initially
Ketone testing: If you feel unwell, particularly with vomiting or abdominal pain
Eye examinations: Regular diabetic retinopathy screening
Your GP or diabetes nurse will establish an appropriate monitoring schedule. Keep a record of any side effects and report persistent or concerning symptoms promptly. Self-monitoring of blood glucose may be recommended depending on your overall diabetes management plan.
If you experience any suspected side effects, you can report them via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or via the Yellow Card app.
Contact your GP or diabetes specialist promptly if you experience any of the following whilst taking Rybelsus and Jardiance together:
Persistent or severe gastrointestinal symptoms: Whilst mild nausea is common with Rybelsus, severe or persistent vomiting, especially if preventing adequate fluid or food intake, requires medical assessment. This may indicate pancreatitis (rare but serious) if accompanied by severe abdominal pain radiating to the back.
Signs of dehydration or volume depletion: Excessive thirst, dizziness upon standing, reduced urine output, dark concentrated urine, or unusual fatigue may indicate dehydration, which can affect kidney function.
Symptoms suggestive of diabetic ketoacidosis: Nausea, vomiting, abdominal pain, unusual tiredness, difficulty breathing, or fruity-smelling breath require urgent medical attention. Check ketones if you have a home testing kit.
Recurrent genital or urinary tract infections: Frequent infections may require treatment adjustment or additional preventive measures.
Severe pain, swelling or redness in the genital or perineal area: Especially if accompanied by fever, this could indicate Fournier's gangrene, a rare but serious infection requiring emergency treatment.
New or worsening visual symptoms: Blurred vision, floaters, or vision loss could indicate retinopathy complications and require prompt assessment.
Hypoglycaemic episodes: If you experience symptoms of low blood glucose (trembling, sweating, confusion, palpitations), particularly if recurrent, your medication doses may need adjustment.
During acute illness or before surgery: You should temporarily stop taking Jardiance during periods of acute illness, especially if you have reduced food or fluid intake, vomiting or diarrhoea. Jardiance should also be paused for at least 3 days before planned surgery. Contact your healthcare team for advice about when to restart.
Routine follow-up is essential even when feeling well. Attend all scheduled diabetes reviews to monitor HbA1c, renal function, and overall treatment effectiveness. Your healthcare team will assess whether the combination continues to meet your therapeutic goals and remains safe based on your evolving health status.
Before starting this combination, ensure your prescriber is aware of your complete medical history, including any history of pancreatitis, severe gastrointestinal disease, recurrent urinary infections, or kidney disease. Inform them of all medications and supplements you take to identify potential interactions. If you are planning pregnancy or become pregnant, contact your diabetes team immediately, as both medications are not recommended during pregnancy and alternative treatments will be needed. Effective contraception should be used while taking these medications if pregnancy is possible.
No, there are no significant pharmacokinetic or pharmacodynamic interactions between Rybelsus (semaglutide) and Jardiance (empagliflozin). They are metabolised through different pathways and can be safely combined under medical supervision.
Take Rybelsus first thing in the morning on an empty stomach with no more than 120 mL of water, wait 30 minutes, then have breakfast and take Jardiance with or after your meal. Jardiance can be taken at any time of day with or without food.
Temporarily stop Jardiance during acute illness (especially with vomiting, diarrhoea, or reduced fluid intake) and at least 3 days before planned surgery to reduce diabetic ketoacidosis risk. Contact your healthcare provider for guidance on when to restart, and continue Rybelsus as directed unless advised otherwise.
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