What is the interaction between Metformin and Jardiance (Empagliflozin)?

From the Guidelines

Metformin and Jardiance (empagliflozin) can be safely used together to manage type 2 diabetes when a single medication isn't providing adequate blood glucose control, as supported by the most recent guidelines from 2025 1.

Key Considerations

• These medications work through different mechanisms: metformin reduces glucose production in the liver and improves insulin sensitivity, while Jardiance helps the kidneys remove excess glucose through urine.
• Typical dosing for metformin ranges from 500-2000 mg daily (often divided into two doses), while Jardiance is usually prescribed as 10 or 25 mg once daily, as outlined in the standards of care for diabetes management 1.
• This combination can provide complementary benefits, including improved glycemic control, potential weight loss, and cardiovascular benefits, with metformin being effective and safe, inexpensive, and widely available, reducing risks of microvascular complications, cardiovascular events, and death 1.
• Patients should be aware that combining these medications may increase the risk of hypoglycemia, though this risk is lower than with some other diabetes medication combinations, and adequate hydration is important when taking Jardiance to prevent dehydration and urinary tract infections.
• Kidney function should be monitored regularly, as both medications have restrictions based on kidney function, with metformin contraindicated with eGFR <30 mL/min/1.73 m² and Jardiance having a glucose-lowering effect that is minimal at eGFR <45 mL/min/1.73 m² 1.

Monitoring and Risk Mitigation

• Patients should report any unusual symptoms like severe nausea, vomiting, abdominal pain, or signs of genital infections promptly to their healthcare provider, and monitoring for hypovolemia and consideration of proactive dose reduction of diuretics in patients at high risk is recommended when using SGLT2 inhibitors like Jardiance 1.
• The risk of diabetic ketoacidosis with SGLT2 inhibitors should be mitigated by educating patients on signs and symptoms, maintaining at least low-dose insulin in insulin-requiring individuals, and considering pausing SGLT2i treatment during periods of acute illness or stressors 1.
• Daily hygienic measures may lessen the risk of genital mycotic infections associated with SGLT2i, and most genital mycotic infections are easily treated, but severe cases of Fournier gangrene have been reported 1.

From the FDA Drug Label

JARDIANCE has been studied as monotherapy and in combination with metformin, sulfonylurea, pioglitazone, linagliptin, and insulin. Add-On Combination Therapy with Metformin A total of 637 patients with type 2 diabetes participated in a double-blind, placebo-controlled study to evaluate the efficacy and safety of JARDIANCE in combination with metformin At Week 24, treatment with JARDIANCE 10 mg or 25 mg daily provided statistically significant reductions in HbA1c (p-value <0. 0001), FPG, and body weight compared with placebo

Metformin and Jardiance can be used in combination. The studies show that JARDIANCE in combination with metformin provides statistically significant reductions in HbA1c, FPG, and body weight compared with placebo 2.

• Key findings:
  • JARDIANCE 10 mg or 25 mg daily in combination with metformin reduces HbA1c.
  • The combination also reduces FPG and body weight.
  • The reduction in HbA1c for JARDIANCE compared with placebo was observed across subgroups including gender, race, geographic region, baseline BMI and duration of disease.

From the Research

Metformin and Jardiance (Empagliflozin) Combination

• The combination of metformin and SGLT2 inhibitors, such as empagliflozin (Jardiance), is used to improve glycemic control in patients with type 2 diabetes 3.
• Empagliflozin has been shown to reduce mortality in patients with type 2 diabetes and significant cardiovascular risk factors, with this benefit not being related to its hypoglycemic effect or prevention of cardiovascular complications of diabetes, but rather to prevention of heart failure in patients with a history of cardiovascular disease 4.
• The combination of metformin and empagliflozin may increase the risk of metabolic acidosis, including lactic acidosis and euglycemic diabetic ketoacidosis 3.

Efficacy and Safety of Empagliflozin

• Empagliflozin is a potent and highly selective SGLT2 inhibitor that offers the convenience of once-daily oral administration and carries a low inherent risk of hypoglycemia 5.
• It has been shown to exert favorable effects on non-glycemic outcomes, including modest reductions in body weight and blood pressure, and has demonstrated cardioprotective and renoprotective properties in patients with type 2 diabetes and established cardiovascular disease 5.
• The most common adverse events associated with empagliflozin are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rare 6.

Clinical Indications for SGLT2 Inhibitors and GLP-1 Receptor Agonists

• SGLT2 inhibitors, such as empagliflozin, and GLP-1 receptor agonists are used in patients with type 2 diabetes as glucose-lowering therapies, with additional benefits of weight loss and blood pressure reduction 7.
• These drugs confer protection against major cardiovascular disease in those with established atherosclerotic cardiovascular disease, reduce the risk of admission to hospital for heart failure, and reduce cardiovascular and all-cause mortality 7.
• Treatment with SGLT2 inhibitors or GLP-1 receptor agonists should be prioritized according to existing evidence, with GLP-1 receptor agonists considered in patients at high risk of or with established cardiovascular disease and SGLT2 inhibitors considered for patients with heart failure or chronic kidney disease 7.