From the Guidelines
Yes, Glyxambi (empagliflozin/linagliptin) can be safely given with metformin 1000mg twice daily. This combination therapy is actually quite common and beneficial for patients with type 2 diabetes who need additional glycemic control. Glyxambi contains two medications that work through different mechanisms: empagliflozin is an SGLT-2 inhibitor that increases glucose excretion through the kidneys, while linagliptin is a DPP-4 inhibitor that increases insulin secretion and decreases glucagon. When combined with metformin, which primarily reduces hepatic glucose production and improves insulin sensitivity, these medications provide complementary actions to lower blood glucose through three distinct pathways.
Key Considerations
- Patients should take Glyxambi once daily in the morning, while continuing their metformin 1000mg twice daily regimen.
- It's essential to monitor kidney function when using this combination, as noted in the 2025 standards of care in diabetes 1.
- Staying well-hydrated is crucial to minimize the risk of dehydration and potential kidney injury.
- Patients should be aware of potential side effects such as urinary tract infections, genital mycotic infections, and hypoglycemia, though the risk of severe hypoglycemia with this combination is relatively low compared to insulin or sulfonylurea combinations.
Evidence-Based Recommendations
The most recent guidelines from the Diabetes Care journal in 2025 1 support the use of metformin as the first-line treatment for type 2 diabetes, with the addition of other agents like SGLT-2 inhibitors and DPP-4 inhibitors for patients who require additional glycemic control. The combination of Glyxambi and metformin is a common and effective treatment strategy, as supported by the standards of care in diabetes-2025 1.
Monitoring and Safety
Regular monitoring of kidney function, as recommended in the 2021 synopsis of the KDIGO clinical practice guideline 1, is vital when using this combination to minimize the risk of kidney injury. Additionally, patients should be educated on the signs and symptoms of potential side effects and the importance of staying hydrated.
Conclusion is not allowed, so the response ends here.
From the FDA Drug Label
Empagliflozin pharmacokinetics were similar with and without coadministration of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, and simvastatin in healthy volunteers and with or without coadministration of hydrochlorothiazide and torsemide in patients with type 2 diabetes Empagliflozin had no clinically relevant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, digoxin, ramipril, simvastatin, hydrochlorothiazide, torsemide, and oral contraceptives when coadministered in healthy volunteers
Glyxambi (empagliflozin/linagliptin) can be given with metformin 1000mg twice daily (bid), as the pharmacokinetics of empagliflozin were similar with and without coadministration of metformin, and empagliflozin had no clinically relevant effect on the pharmacokinetics of metformin 2.
- Key points:
- Empagliflozin and metformin can be coadministered.
- No dose adjustment of empagliflozin is recommended when coadministered with metformin.
From the Research
Combination Therapy with Glyxambi and Metformin
- The combination of empagliflozin and linagliptin (Glyxambi) with metformin has been studied in several clinical trials 3, 4, 5, 6.
- A study published in Diabetes Care in 2015 found that the combination of empagliflozin 10 mg/linagliptin 5 mg as add-on to metformin resulted in significant reductions in HbA1c compared to empagliflozin or linagliptin alone as add-on to metformin 3.
- Another study published in Drugs in 2015 reviewed the clinical efficacy and tolerability of oral empagliflozin/linagliptin in patients with type 2 diabetes and found that the combination improved glycemic control significantly more than linagliptin when administered as initial therapy or as an add-on therapy to metformin 4.
- A bioequivalence study published in Postgraduate Medicine in 2020 found that a triple fixed-dose combination of empagliflozin, linagliptin, and metformin was bioequivalent to the corresponding free combinations, suggesting that the combination can be safely used in patients with type 2 diabetes 5.
- A systematic review and meta-analysis published in Diabetes, Obesity & Metabolism in 2020 found that the combination of empagliflozin and linagliptin had superior efficacy and similar safety compared to either monotherapy in achieving euglycaemia in patients with type 2 diabetes 6.
Dosage and Administration
- The recommended dosage of Glyxambi is 10 mg/5 mg or 25 mg/5 mg once daily, taken in the morning 4.
- Metformin can be administered at a dosage of 1000 mg twice daily, as part of a combination therapy with Glyxambi 5.
- The combination of Glyxambi and metformin can be used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes 3, 4, 5, 6.
Safety and Efficacy
- The combination of Glyxambi and metformin has been found to be well-tolerated, with a low risk of hypoglycemia and no reports of exacerbations of, or hospitalizations for, heart failure 3, 4, 6.
- The combination has been shown to provide significant reductions in HbA1c, as well as improvements in weight and blood pressure, compared to either monotherapy 3, 4, 6.