What is the next best oral medication option for a patient with hyperglycemia who is currently taking metformin, Trulicity (dulaglutide) 3 mg weekly, and insulin glargine and insulin lispro?

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Last updated: February 26, 2025 • View editorial policy

From the Guidelines

For a patient with hyperglycemia already on metformin, Trulicity (dulaglutide) 3 mg weekly, and both basal (insulin glargine) and bolus (insulin lispro) insulins, the next best oral medication option would be an SGLT-2 inhibitor such as empagliflozin (Jardiance) 10-25 mg daily or dapagliflozin (Farxiga) 5-10 mg daily. This recommendation is based on the most recent and highest quality study available, which highlights the benefits of SGLT-2 inhibitors in patients with type 2 diabetes, including those with established cardiovascular disease, heart failure, or chronic kidney disease 1. Some key points to consider when prescribing SGLT-2 inhibitors include:

  • Monitoring for genital mycotic infections, urinary tract infections, and volume depletion, especially in elderly patients
  • Advising patients about proper genital hygiene and adequate hydration
  • Adjusting insulin doses as needed after starting this medication due to its glucose-lowering effect
  • Being aware of the potential benefits of SGLT-2 inhibitors, including cardiovascular benefits, heart failure risk reduction, and renal protection According to the study, SGLT-2 inhibitors have a low risk of hypoglycemia and can promote modest weight loss, making them a suitable option for patients with hyperglycemia who are already on multiple medications 1. Additionally, the study provides guidance on dose adjustments for patients with chronic kidney disease, which is an important consideration when prescribing SGLT-2 inhibitors 2. Overall, the use of SGLT-2 inhibitors as an add-on therapy to metformin, GLP-1 receptor agonists, and insulin can provide significant benefits for patients with type 2 diabetes, and their use should be considered in the context of individual patient needs and medical history.

From the FDA Drug Label

In Combination with Insulin (18 weeks) Placebo (N=565) INVOKANA 100 mg (N=566) INVOKANA 300 mg (N=587) Overall [N (%)]208 (36.8)279 (49. 3)285 (48.6) Severe [N (%)] †14 (2.5)10 (1.8)16 (2.7)

The next best oral medication option for a patient with hyperglycemia who is currently taking metformin, Trulicity (dulaglutide) 3 mg weekly, and insulin glargine and insulin lispro could be canagliflozin (INVOKANA), as it has been studied in combination with insulin. However, it's essential to consider the potential risks, such as:

  • Hypoglycemia: The incidence of hypoglycemia was higher when INVOKANA was co-administered with insulin.
  • Bone fracture: The incidence rates of all adjudicated bone fracture were higher with INVOKANA compared to placebo.
  • Laboratory and imaging tests: Increases in serum creatinine and decreases in eGFR, as well as increases in serum potassium, have been observed with INVOKANA. 3

From the Research

Current Treatment Regimen

The patient is currently taking metformin, Trulicity (dulaglutide) 3 mg weekly, and insulin glargine and insulin lispro.

Next Best Oral Medication Option

Considering the patient's current treatment regimen, the next best oral medication option is not explicitly stated in the provided studies. However, some key points can be considered:

  • Metformin is already being taken by the patient, and it is associated with decreased weight gain, lower insulin dose, and less hypoglycemia when combined with insulin 4.
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors can be used in combination with metformin and insulin glargine, resulting in significant improvement of glycemic control 5.
  • Glucagon-like peptide-1 (GLP-1) receptor agonists, such as dulaglutide, can be used in combination with insulin lispro, resulting in improved glycemic control 6.

Potential Options

Some potential oral medication options that can be considered are:

  • DPP-4 inhibitors, such as sitagliptin or saxagliptin, which can be used in combination with metformin and insulin glargine.
  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as canagliflozin or empagliflozin, which can be used in combination with metformin and insulin.
  • Pioglitazone, a thiazolidinedione, which can be used in combination with metformin and insulin.

Important Considerations

When selecting the next best oral medication option, it is essential to consider the patient's individual needs, medical history, and potential interactions with their current medications. The patient's glycemic control, weight, and risk of hypoglycemia should also be taken into account 4, 5, 6, 7, 8.

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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.