Can Pioglitazone (Actos) be taken concurrently with Dapagliflozin (Farxiga) and Metformin?

From the Guidelines

Yes, Actos (pioglitazone) can generally be taken concurrently with Farxiga (dapagliflozin) and metformin for diabetes management, as supported by the most recent guidelines 1. This combination therapy targets different aspects of blood glucose control: Actos improves insulin sensitivity, Farxiga increases glucose excretion through the kidneys, and metformin reduces glucose production by the liver and improves insulin sensitivity. However, this three-drug combination should only be used under medical supervision as it may increase the risk of certain side effects, including hypoglycemia (low blood sugar), fluid retention, and heart failure, particularly in patients with cardiovascular disease. Key considerations for this combination include:

• The patient's specific health status, including the presence of cardiovascular disease, kidney function, and blood glucose levels.
• Regular monitoring of blood glucose, kidney function, and heart health is essential when taking this combination.
• Potential side effects such as hypoglycemia, fluid retention, and heart failure, and the need for individualized dosing by a healthcare provider.
• The importance of patient education on recognizing and managing potential side effects, such as diabetic ketoacidosis, acute kidney injury, dehydration, and orthostatic hypotension, as noted in previous studies 1.
• The consideration of cost, efficacy, and patient preferences in the choice of pharmacologic treatment, as outlined in recent guidelines 1. If you experience symptoms like unusual swelling, shortness of breath, or frequent low blood sugar episodes, contact your healthcare provider immediately. It's also important to note that the use of SGLT2 inhibitors, such as Farxiga, requires intermittent monitoring of renal function, and caution should be taken when used in combination with diuretics and/or ACE inhibitors and angiotensin receptor blockers, as highlighted in previous reports 1. Overall, the decision to use Actos, Farxiga, and metformin together should be made on a case-by-case basis, taking into account the individual patient's needs and health status, and under the guidance of a healthcare provider, with consideration of the most recent guidelines and evidence 1.

From the FDA Drug Label

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 (NCT00683878) In combination with pioglitazone, treatment with dapagliflozin 10 mg provided statistically significant improvements in HbA1c, 2-hour PPG, FPG, the proportion of patients achieving HbA1c <7%, and a statistically significant reduction in body weight compared with the placebo plus pioglitazone treatment groups

• Key Points:
  • Dapagliflozin (Farxiga) can be taken concurrently with pioglitazone (a thiazolidinedione, the class of medication that Actos belongs to).
  • The combination of dapagliflozin and pioglitazone provided statistically significant improvements in HbA1c and other endpoints.
  • Additionally, dapagliflozin can be taken concurrently with metformin, as shown in other parts of the label.
• Conclusion: Based on the information provided, Actos (pioglitazone) can be taken concurrently with Farxiga (dapagliflozin) and metformin 2.

From the Research

Combination Therapy with Actos, Farxiga, and Metformin

• The use of combination therapy for type 2 diabetes management is a common approach to achieve better glycemic control and reduce cardiovascular risk factors.
• Studies have shown that dapagliflozin (Farxiga) can be used as an add-on therapy to metformin, and also as a combination with other glucose-lowering agents, including insulin 3, 4.
• Pioglitazone (Actos) is a thiazolidinedione that can be used in combination with metformin for the treatment of type 2 diabetes, and has been shown to improve insulin sensitivity and glycemic control 5, 6.
• A study comparing the efficacy and safety of pioglitazone/metformin combination with dapagliflozin versus basal insulin/metformin found that the combination of pioglitazone/metformin with dapagliflozin was a safe and effective alternative to basal insulin combined with metformin for patients with inadequately controlled type 2 diabetes 5.
• Another study found that a fixed combination of metformin and pioglitazone provided greater improvement in insulin resistance than metformin alone, and similar changes in insulin resistance to dapagliflozin 6.

Safety and Efficacy

• The combination of pioglitazone, metformin, and dapagliflozin has been shown to be safe and effective in improving glycemic control and reducing cardiovascular risk factors 5.
• However, the use of dapagliflozin has been associated with an increased risk of urinary tract infections and genital infections 3, 4.
• Pioglitazone has been associated with an increased risk of heart failure and fractures, and should be used with caution in patients with a history of these conditions 5, 6.

Clinical Implications

• The combination of Actos, Farxiga, and metformin may be a viable treatment option for patients with type 2 diabetes who require multiple medications to achieve glycemic control.
• However, the decision to use this combination should be made on a case-by-case basis, taking into account the individual patient's medical history, current medications, and potential risks and benefits 5, 6.