Rybelsus (semaglutide) and Jardiance (empagliflozin) can generally be taken together for adults with type 2 diabetes mellitus. This combination is increasingly prescribed as both medications work through different mechanisms to improve glycaemic control. Rybelsus, a glucagon-like peptide-1 (GLP-1) receptor agonist, stimulates insulin secretion and reduces appetite, whilst Jardiance, an SGLT2 inhibitor, increases urinary glucose excretion and offers cardiovascular protection. No clinically relevant pharmacological interaction prevents their concurrent use. NICE guidance acknowledges that combination therapy with agents from different drug classes may be necessary to achieve optimal HbA1c targets. This article explores safety considerations, monitoring requirements, and practical guidance for patients taking both medications.

Can Rybelsus Be Taken With Jardiance?

Yes, Rybelsus (semaglutide) and Jardiance (empagliflozin) can generally be taken together, and this combination is increasingly prescribed for adults with type 2 diabetes mellitus. Both medications work through different mechanisms to improve glycaemic control, making them complementary rather than conflicting in their actions.

Rybelsus belongs to a class of medicines called glucagon-like peptide-1 (GLP-1) receptor agonists. It works by stimulating insulin secretion when blood glucose levels are elevated, suppressing glucagon release, slowing gastric emptying, and reducing appetite. This oral formulation of semaglutide is typically taken once daily on an empty stomach, at least 30 minutes before food or other medications.

Jardiance is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that works independently of insulin by blocking glucose reabsorption in the kidneys, thereby increasing urinary glucose excretion. It also provides cardiovascular and renal protective benefits, which have been demonstrated in clinical trials. Jardiance is taken once daily and can be administered with or without food.

No clinically relevant pharmacological interaction is expected between these two medications that would prevent their concurrent use. NICE guidance (NG28) on type 2 diabetes management acknowledges that combination therapy with agents from different drug classes may be necessary to achieve optimal HbA1c targets. Many patients require dual or triple therapy when metformin alone proves insufficient, and the pairing of a GLP-1 receptor agonist with an SGLT2 inhibitor typically represents part of a stepwise treatment intensification approach to address multiple pathophysiological aspects of diabetes.

Safety Considerations When Combining These Medications

Whilst Rybelsus and Jardiance can be safely combined, several important safety considerations warrant attention. The primary concern is the cumulative risk of hypoglycaemia, particularly if you are also taking other glucose-lowering medications such as sulphonylureas (e.g., gliclazide) or insulin. Both Rybelsus and Jardiance have a low intrinsic risk of hypoglycaemia when used alone, but adding them to existing therapy may necessitate dose adjustments of other diabetes medications.

Dehydration and volume depletion represent another consideration. Jardiance increases urinary output due to its mechanism of action, whilst Rybelsus may cause gastrointestinal side effects including nausea, vomiting, and diarrhoea, especially during treatment initiation. The combination of increased urination and potential fluid losses through gastrointestinal symptoms could theoretically increase dehydration risk. Patients should be advised to maintain adequate fluid intake and be vigilant for signs of dehydration such as dizziness, particularly when standing, or reduced urine output.

Diabetic ketoacidosis (DKA) is a rare but serious adverse effect associated with SGLT2 inhibitors, including Jardiance. This can occur even when blood glucose levels are not markedly elevated (euglycaemic DKA). Risk factors include very low-carbohydrate diets, dehydration, reduced insulin doses, surgery, and acute illness. Warning signs include excessive thirst, frequent urination, nausea, vomiting, abdominal pain, confusion, unusual fatigue, or difficulty breathing. If these symptoms develop, seek immediate medical attention.

SGLT2 inhibitors should be temporarily stopped during periods of acute illness, dehydration, or fasting, and for at least 3 days before planned surgery or procedures requiring anaesthesia. This 'sick day rule' helps reduce DKA risk.

Renal function monitoring is essential with both medications. For Jardiance, the glycaemic efficacy declines with decreasing kidney function, and specific eGFR thresholds apply depending on whether it's being used for diabetes, heart failure, or chronic kidney disease. Rybelsus should be used with caution in renal disease. Regular monitoring of kidney function is recommended, particularly in elderly patients or those with pre-existing renal compromise.

Rare but serious cases of Fournier's gangrene (a necrotising infection of the genitalia) have been reported with SGLT2 inhibitors. Seek urgent medical attention if you experience severe pain, tenderness, redness, or swelling in the genital or perineal area, accompanied by fever or malaise.

Patients with pre-existing diabetic retinopathy should be monitored closely when using semaglutide, as rapid improvements in glucose control may temporarily worsen retinopathy.

What to Discuss With Your Healthcare Provider

Before starting or continuing treatment with both Rybelsus and Jardiance, a comprehensive discussion with your healthcare provider is essential. Your complete medical history should be reviewed, with particular attention to kidney function, history of pancreatitis, thyroid disorders (semaglutide should be used with caution in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2), cardiovascular disease, and any history of diabetic ketoacidosis.

Current medications must be thoroughly reviewed, as certain drug interactions may require consideration. Rybelsus can delay gastric emptying, potentially affecting the absorption of oral medications, particularly those requiring rapid absorption or those with a narrow therapeutic index. For example, levothyroxine exposure may increase, and INR should be monitored if taking warfarin. Your healthcare provider may need to adjust timing of other medications or monitor their effects more closely. All oral medications should be taken at least 30 minutes after Rybelsus. Inform your prescriber about all medications, including over-the-counter products and herbal supplements.

Discuss your diabetes management goals and current glycaemic control. Your HbA1c level, frequency of hypoglycaemic episodes, weight trajectory, and overall diabetes control will influence whether this combination is appropriate. If you're taking insulin or sulphonylureas, dose reductions may be necessary to minimise hypoglycaemia risk when adding these medications.

Lifestyle factors and practical considerations should also be addressed. Rybelsus requires specific administration instructions (taken on an empty stomach with no more than 120ml of water, waiting at least 30 minutes before eating or taking other medications), which may not suit everyone's routine. Discuss whether you can realistically adhere to these requirements.

If you are pregnant, planning pregnancy, or breastfeeding, discuss alternative diabetes treatments. Generally, GLP-1 receptor agonists and SGLT2 inhibitors are not recommended during pregnancy or breastfeeding, with insulin being the preferred option for managing diabetes during pregnancy.

Establish a perioperative plan if you have surgery scheduled. SGLT2 inhibitors should typically be paused at least 3 days before planned procedures requiring anaesthesia.

Finally, ensure you understand warning signs requiring urgent medical attention, including symptoms of DKA, severe hypoglycaemia, pancreatitis (severe persistent abdominal pain), genital infections, or signs of Fournier's gangrene. Establish clear plans for sick-day management, as both medications may require temporary discontinuation during acute illness.

Monitoring and Managing Side Effects

Effective monitoring is crucial when taking Rybelsus and Jardiance together. Blood glucose monitoring should be individualised based on your treatment regimen and circumstances. More frequent self-monitoring is advisable when starting or adjusting therapy, particularly if you're also taking sulphonylureas or insulin which increase hypoglycaemia risk.

Gastrointestinal side effects are common with Rybelsus, particularly during the first few weeks of treatment. These typically include nausea, vomiting, diarrhoea, abdominal pain, and reduced appetite. To minimise these effects:

• Start with the lowest dose (3mg) and increase gradually as prescribed

• Eat smaller, more frequent meals

• Avoid high-fat or spicy foods initially

• Stay well hydrated

• Take the medication consistently each morning

Most gastrointestinal symptoms improve over time as your body adjusts. However, if symptoms are severe or persistent, contact your GP, as dose adjustment may be necessary.

Genital and urinary tract infections occur more frequently with Jardiance due to increased glucose in the urine. Maintain good personal hygiene, stay well hydrated, and seek prompt treatment if symptoms develop (pain during urination, unusual discharge, itching, or redness). Women and uncircumcised men are at higher risk.

Regular clinical monitoring should include:

• HbA1c measurements every 3–6 months

• Renal function tests (eGFR and creatinine) at least annually, or more frequently if impaired

• Blood pressure monitoring

• Weight tracking

• Foot examinations

• Regular diabetic eye screening, especially if you have pre-existing retinopathy

During acute illness, particularly if you're unable to maintain normal fluid and food intake, temporarily stop your Jardiance and contact your healthcare team for advice. This 'sick day rule' helps reduce the risk of dehydration and diabetic ketoacidosis.

Contact your GP or diabetes team promptly if you experience persistent vomiting or diarrhoea, signs of dehydration, symptoms suggestive of DKA, severe abdominal pain, recurrent infections, or new or worsening visual symptoms. Never discontinue these medications without medical advice, but do seek guidance if you're unwell or experiencing concerning symptoms.

If you suspect any adverse effects from your medication, you can report them through the MHRA Yellow Card scheme.

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