What medication can be added to Jardiance (Empagliflozin) and metformin for a patient with persistent hyperglycemia?

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Last updated: March 14, 2025 • View editorial policy

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From the Guidelines

For a patient already on Jardiance (empagliflozin) and metformin with persistently high A1c, adding a GLP-1 receptor agonist would be an excellent choice, as it has been shown to provide synergistic benefits with SGLT2 inhibitors in improving glycemic control and reducing cardiovascular risk 1.

Key Considerations

  • The choice of medication added to metformin and Jardiance should be based on the clinical characteristics of the patient and their preferences, including the presence of established ASCVD or indicators of high ASCVD risk, heart failure, CKD, and other comorbidities 1.
  • GLP-1 receptor agonists, such as once-weekly semaglutide (Ozempic), once-weekly dulaglutide (Trulicity), or daily liraglutide (Victoza), are suitable options, as they promote insulin secretion, suppress glucagon, slow gastric emptying, and reduce appetite, while also providing cardiovascular and renal protection 1.
  • The combination of a GLP-1 receptor agonist with an SGLT2 inhibitor like Jardiance is particularly beneficial, as it addresses multiple pathophysiological defects in type 2 diabetes, including improved glycemic control, weight loss, and reduced cardiovascular risk 1.

Treatment Options

  • Once-weekly semaglutide (Ozempic, starting at 0.25mg and titrating to 0.5-1mg)
  • Once-weekly dulaglutide (Trulicity, starting at 0.75mg and increasing to 1.5mg)
  • Daily liraglutide (Victoza, starting at 0.6mg and titrating to 1.2-1.8mg)

Important Considerations

  • Start with the lowest dose and titrate slowly to minimize gastrointestinal side effects, such as nausea, vomiting, and diarrhea, which typically improve over time 1.
  • If GLP-1 agonists are not suitable, alternatives include adding a DPP-4 inhibitor (like sitagliptin) or basal insulin, though these may be less effective for comprehensive metabolic improvement 1.

From the FDA Drug Label

In Combination with Linagliptin as Add-On to Metformin Therapy A total of 686 patients with type 2 diabetes participated in a double-blind, active-controlled study to evaluate the efficacy and safety of JARDIANCE 10 mg or 25 mg in combination with linagliptin 5 mg compared to the individual components At Week 24, JARDIANCE 10 mg or 25 mg used in combination with linagliptin 5 mg provided statistically significant improvement in HbA1c (p-value <0.0001) and FPG (p-value <0. 001) compared to the individual components in patients who had been inadequately controlled on metformin.

Medication that can be added to Jardiance (Empagliflozin) and metformin:

  • Linagliptin: can be added to Jardiance (Empagliflozin) and metformin for a patient with persistent hyperglycemia, as it has been shown to provide statistically significant improvement in HbA1c and FPG compared to the individual components in patients who had been inadequately controlled on metformin 2.

From the Research

Medication Options for Persistent Hyperglycemia

When a patient is already taking Jardiance (Empagliflozin) and metformin, several medication options can be considered to manage persistent hyperglycemia:

  • GLP-1 receptor agonists (GLP-1RAs) such as exenatide, liraglutide, albiglutide, or dulaglutide can be added to the existing treatment regimen 3
  • These agents have been shown to lower A1C levels, promote weight loss, and improve cardiovascular risk markers 3
  • GLP-1RAs can be used in combination with other oral glucose-lowering agents or basal insulin 3

Efficacy of GLP-1RAs Compared to Insulin

Studies have compared the efficacy of GLP-1RAs to insulin in patients with type 2 diabetes:

  • The DURATION-3 and LEAD-5 studies found that exenatide QW and liraglutide, respectively, led to greater reductions in HbA1c levels compared to insulin glargine 4
  • Another study found that dulaglutide had a superior HbA1c-lowering effect compared to insulin glargine 4
  • GLP-1RAs are also associated with weight loss, whereas insulin treatment is often associated with weight gain 4

Comparison of Semaglutide and Empagliflozin

A patient-level meta-analysis compared the efficacy of once-weekly semaglutide to empagliflozin in patients with type 2 diabetes:

  • The analysis found that semaglutide significantly reduced HbA1c levels and body weight compared to empagliflozin 5
  • Semaglutide may be a suitable option for patients who are already taking metformin and require additional glucose-lowering therapy 5

Safety and Efficacy of Glucose-Lowering Drugs

A meta-analysis compared the safety and efficacy of various glucose-lowering drugs, including GLP-1RAs and SGLT-2 inhibitors:

  • The analysis found that metformin was associated with lower HbA1c levels compared to other drug classes 6
  • SGLT-2 inhibitors, such as empagliflozin, were found to have a low risk of hypoglycemia when added to metformin 6
  • GLP-1RAs were associated with a low risk of hypoglycemia when added to metformin and sulfonylurea 6

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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