What additional diabetes medications can be added to a patient with diabetes on Farxiga (dapagliflozin) 10 mg and glipizide 10 mg with an Hemoglobin A1c (HbA1c) of 8.5%?

From the Guidelines

For a patient with diabetes on Farxiga (dapagliflozin) 10 mg and glipizide 10 mg with an HbA1c of 8.5%, adding a glucagon-like peptide-1 (GLP-1) receptor agonist would be the most appropriate next step. According to the standards of medical care in diabetes-2020 1, combination therapy is often necessary for patients with type 2 diabetes, and the choice of medication added to the existing regimen should be based on the clinical characteristics of the patient and their preferences.

Some key points to consider when adding a new medication include:

• The presence of established ASCVD or indicators of high ASCVD risk
• Other comorbidities
• Risk for specific adverse drug effects
• Safety, tolerability, and cost
• The patient's preferences

Options for GLP-1 receptor agonists include semaglutide (Ozempic) starting at 0.25 mg weekly for 4 weeks, then increasing to 0.5 mg weekly, or dulaglutide (Trulicity) starting at 0.75 mg weekly and increasing to 1.5 mg weekly if needed. Alternatively, a once-daily GLP-1 agonist like liraglutide (Victoza) starting at 0.6 mg daily for one week, then increasing to 1.2 mg daily could be used.

Adding a GLP-1 agonist provides complementary action to the existing medications by promoting insulin secretion in a glucose-dependent manner, suppressing glucagon, delaying gastric emptying, and reducing appetite. This combination is particularly effective because the patient already has an SGLT-2 inhibitor (Farxiga) which works on the kidneys to increase glucose excretion, and a sulfonylurea (glipizide) which stimulates insulin release. If GLP-1 agonists are contraindicated or not tolerated, adding basal insulin (like insulin glargine 10 units at bedtime, titrated weekly based on fasting glucose) would be another reasonable option, as suggested by the standards of medical care in diabetes-2020 1.

From the FDA Drug Label

Add-On Combination Therapy with a Sulfonylurea A total of 597 adult patients with type 2 diabetes mellitus and inadequate glycemic control (HbA1c ≥7% and ≤10%) were randomized in this 24-week, placebo-controlled trial to evaluate dapagliflozin in combination with glimepiride (a sulfonylurea) Add-On Combination Therapy with Metformin and a Sulfonylurea A total of 218 adult patients with type 2 diabetes mellitus and inadequate glycemic control (HbA1c ≥7% and ≤10.5%) participated in a 24-week, placebo-controlled trial to evaluate dapagliflozin in combination with metformin and a sulfonylurea Add-On Combination Therapy with a Thiazolidinedione A total of 420 adult patients with type 2 diabetes mellitus with inadequate glycemic control (HbA1c ≥7% and ≤10.5%) participated in a 24-week, placebo-controlled trial to evaluate dapagliflozin in combination with pioglitazone [a thiazolidinedione (TZD)] alone Add-On Combination Therapy with a DPP4 Inhibitor A total of 452 adult patients with type 2 diabetes mellitus who were drug naive, or who were treated at entry with metformin or a DPP4 inhibitor alone or in combination, and had inadequate glycemic control (HbA1c ≥7.0% and ≤10. Add-On Combination Therapy with Insulin A total of 808 adult patients with type 2 diabetes mellitus who had inadequate glycemic control (HbA1c ≥7.5% and ≤10.5%) were randomized in a 24-week, placebo-controlled trial to evaluate dapagliflozin as add-on therapy to insulin

The patient is already on Farxiga (dapagliflozin) 10 mg and glipizide 10 mg. Considering the patient's current medication regimen and the provided drug label information, potential additional diabetes medications that can be added include:

• Metformin: as part of a combination with a sulfonylurea
• Pioglitazone: a thiazolidinedione
• Sitagliptin: a DPP4 inhibitor
• Insulin: as part of a combination with or without up to 2 oral antidiabetic therapies It is essential to carefully evaluate the patient's specific situation, considering factors such as their current medication regimen, potential drug interactions, and individual health needs, before adding any new medication. 2 2

From the Research

Additional Diabetes Medications

To manage a patient with diabetes on Farxiga (dapagliflozin) 10 mg and glipizide 10 mg with an Hemoglobin A1c (HbA1c) of 8.5%, several additional diabetes medications can be considered:

• Metformin: As a first-line treatment for type 2 diabetes, metformin can be added to dapagliflozin and glipizide to improve glycemic control 3, 4, 5, 6.
• Pioglitazone: A thiazolidinedione that can be used in combination with dapagliflozin and glipizide to improve insulin sensitivity and glycemic control 4, 5, 6.
• Glucagon-like peptide-1 (GLP-1) receptor agonists: Such as exenatide or liraglutide, which can be used to improve glycemic control and promote weight loss 7.
• Sodium-glucose cotransporter 2 (SGLT2) inhibitors: Although the patient is already on dapagliflozin, another SGLT2 inhibitor like canagliflozin can be considered if the patient's glycemic control is not adequate 7.
• Insulin: Although insulin is often considered for patients with HbA1c >9%, it may not be the preferred treatment for patients with HbA1c <9% 7.

Considerations for Adding New Medications

When adding new medications to the patient's regimen, consider the following:

• The patient's current medication regimen and potential interactions with new medications.
• The patient's renal function, as dapagliflozin is not recommended in patients with moderate or severe renal impairment 5.
• The patient's risk of hypoglycemia, genital infections, and urinary tract infections, which are potential side effects of dapagliflozin and other diabetes medications 3, 4, 5, 6.
• The patient's weight and potential for weight loss with certain medications, such as GLP-1 receptor agonists 7.