Can I start Synjardy (empagliflozin and metformin) as first-line therapy with a hemoglobin A1c (HbA1c) level of 13.1?

From the Guidelines

Starting Synjardy (empagliflozin and metformin) as first-line therapy for a patient with an HbA1c of 13.1% is a viable option, but given the high level of HbA1c, more aggressive treatment, possibly including insulin, should be considered initially. For patients with significantly elevated HbA1c levels, such as 13.1%, the American Diabetes Association recommends considering initial combination therapy or insulin to achieve rapid glycemic control 1. The choice of medication should be based on the patient's clinical characteristics, preferences, and the presence of comorbidities such as ASCVD, HF, or CKD. Key considerations include:

• The potential benefits and risks of each medication, including the risk of hypoglycemia and weight gain
• The cost and accessibility of the medication
• The individual's preferences and ability to adhere to the treatment regimen If Synjardy is chosen, the typical starting dose is empagliflozin 5 mg/metformin 500 mg twice daily, which can be gradually increased as tolerated to minimize gastrointestinal side effects 1. Given the high HbA1c level, the provider might consider starting at a higher dose of empagliflozin 12.5 mg/metformin 1000 mg twice daily. Close monitoring with follow-up within 2-4 weeks is necessary to assess the response and potentially adjust therapy. Synjardy's dual mechanism of action, combining metformin and empagliflozin, can effectively lower blood sugar, but may not be sufficient alone for severely elevated levels, thus comprehensive diabetes management including diet, exercise, and blood glucose monitoring should also be discussed with the healthcare provider 1.

From the Research

Initial Combination Therapy with Synjardy

• The study 2 compared the efficacy and safety of initial combinations of empagliflozin and metformin in patients with type 2 diabetes, with a baseline HbA1c >7.5 to ≤12%.
• The results showed that initial combinations of empagliflozin and metformin significantly reduced HbA1c versus empagliflozin once daily and metformin twice daily, without increased hypoglycemia, and reduced weight versus metformin twice daily.
• However, the study did not specifically address the use of Synjardy as first-line therapy with a baseline HbA1c of 13.1.

Use of Insulin in Patients with HbA1c >9%

• The study 3 discussed the use of insulin in patients with type 2 diabetes and HbA1c >9%, and suggested that insulin may not always be the preferred treatment option.
• The study noted that dual oral agent approaches, such as metformin plus a sulfonylurea, pioglitazone, or sitagliptin, can be effective in reducing HbA1c levels, even in patients with baseline HbA1c >11%.
• However, the study did not specifically address the use of Synjardy as first-line therapy with a baseline HbA1c of 13.1.

Combination Therapy with SGLT2 Inhibitors and Metformin

• The study 4 compared the clinical effectiveness of combined therapy using SGLT2 inhibitors and metformin with monotherapy using metformin alone in HbA1c and body weight reduction.
• The results showed that combined therapy was more effective in HbA1c reduction and weight reduction as compared to monotherapy.
• Empagliflozin 25mg was found to be effective in HbA1c reduction, but the study did not specifically address the use of Synjardy as first-line therapy with a baseline HbA1c of 13.1.

Comparison of Empagliflozin and Dulaglutide

• The study 5 compared the effectiveness and safety of empagliflozin and dulaglutide in patients with type 2 diabetes inadequately controlled with metformin, sulfonylurea, and DPP4 inhibitor.
• The results showed that empagliflozin demonstrated greater HbA1c reduction and weight loss compared to dulaglutide.
• However, the study did not specifically address the use of Synjardy as first-line therapy with a baseline HbA1c of 13.1.

Empagliflozin as Add-on to Metformin plus Sulphonylurea

• The study 6 investigated the long-term efficacy and safety of empagliflozin as add-on to metformin plus sulphonylurea in patients with type 2 diabetes.
• The results showed that empagliflozin led to sustained reductions in HbA1c and weight versus placebo, but the study did not specifically address the use of Synjardy as first-line therapy with a baseline HbA1c of 13.1.

Considerations for Starting Synjardy as First-Line Therapy

• Based on the available evidence, it appears that Synjardy may be a viable option for first-line therapy in patients with type 2 diabetes, but the decision to start Synjardy should be individualized and based on the patient's specific clinical characteristics and needs.
• The studies suggest that combination therapy with SGLT2 inhibitors and metformin can be effective in reducing HbA1c levels and weight, but the use of Synjardy as first-line therapy with a baseline HbA1c of 13.1 is not specifically addressed in the available evidence 2, 3, 4, 5, 6.