Is empagliflozin (Jardiance) 10 mg plus pioglitazone (Actos) 15 mg a good combination for type 2 diabetes management?

From the Guidelines

Empagliflozin (Jardiance) 10 mg plus pioglitazone (Actos) 15 mg can be a beneficial combination for type 2 diabetes management in selected patients, particularly those with insulin resistance and cardiovascular disease, as evidenced by the most recent guidelines 1. This combination pairs two medications with complementary mechanisms of action: empagliflozin is an SGLT2 inhibitor that increases glucose excretion through the kidneys, while pioglitazone is a thiazolidinedione that improves insulin sensitivity in peripheral tissues. Together, they can provide better glycemic control than either medication alone, with empagliflozin also offering cardiovascular benefits as demonstrated in studies such as EMPA-REG OUTCOME and EMPEROR-Reduced 1. However, it's crucial to consider the patient's comorbidities and potential side effects, including the risk of heart failure with pioglitazone, especially in patients with pre-existing heart conditions, as highlighted in earlier guidelines and studies 1. Regular monitoring of renal function, weight, and signs of fluid retention is essential when using this combination, and the decision to use this regimen should be individualized based on the latest clinical evidence and patient-specific factors 1. The most recent standards of care in diabetes support the use of combination therapy for more rapid attainment of glycemic goals and for longer-term management, considering person-specific factors and the potential benefits and risks of each medication 1.

From the FDA Drug Label

A total of 498 patients with type 2 diabetes mellitus participated in a double-blind, placebo-controlled trial to evaluate the efficacy of JARDIANCE in combination with pioglitazone, with or without metformin Patients with inadequately controlled type 2 diabetes mellitus on metformin at a dose of at least 1,500 mg per day and pioglitazone at a dose of at least 30 mg per day were placed into an open-label placebo run-in for 2 weeks. Patients with inadequate glycemic control and an HbA1c between 7% and 10% after the run-in period were randomized to placebo, JARDIANCE 10 mg, or JARDIANCE 25 mg Treatment with JARDIANCE 10 mg or 25 mg daily resulted in statistically significant reductions in HbA1c (p-value <0. 0001), FPG, and body weight compared with placebo

Combination of empagliflozin and pioglitazone is a viable option for type 2 diabetes management, as it has been shown to result in statistically significant reductions in HbA1c, FPG, and body weight compared to placebo 2.

• The study used JARDIANCE 10 mg and JARDIANCE 25 mg in combination with pioglitazone, with or without metformin.
• The results showed that JARDIANCE 10 mg daily resulted in a statistically significant reduction in HbA1c, FPG, and body weight compared to placebo.
• However, the dose of pioglitazone used in the study was at least 30 mg per day, which is higher than the 15 mg mentioned in the question.
• Therefore, the efficacy and safety of empagliflozin 10 mg plus pioglitazone 15 mg cannot be directly concluded from the study.

From the Research

Combination Therapy for Type 2 Diabetes Management

The combination of empagliflozin 10 mg and pioglitazone 15 mg for type 2 diabetes management has been studied in various clinical trials.

• The addition of empagliflozin to pioglitazone or pioglitazone plus metformin treatment may offer some advantages, including significant reductions in glycated hemoglobin levels, weight, and blood pressure, with a low risk of hypoglycemia 3.
• Pioglitazone is a valuable component of combination therapy for type 2 diabetes mellitus, improving glycemic control with an extremely low incidence of hypoglycemia, and exhibiting favorable pleiotropic effects such as anti-inflammatory, antioxidant, vasoprotective, antihypertensive, and hypolipidemic actions 4.
• Empagliflozin has been shown to be effective in reducing blood glucose levels, weight, and blood pressure, with a low risk of hypoglycemia, but is associated with an increased risk of events consistent with genital mycotic infections 5, 6, 3.
• The safety and efficacy of empagliflozin as add-on therapy to other medications, such as GLP-1 receptor agonists, have also been demonstrated in clinical trials 7.

Key Considerations

• The combination of empagliflozin and pioglitazone may be beneficial for patients with type 2 diabetes mellitus, but care should be taken to ensure that the treatment is appropriate for the individual patient's characteristics 5.
• Patients should be monitored for potential side effects, such as genital mycotic infections, and hypoglycemia when combined with sulfonylurea 6.
• The treatment should be discontinued in patients with an estimated glomerular filtration rate (eGFR) below 45 ml/min/1.73 m2 6.