Is dual therapy with Jardiance (Empagliflozin) and Metformin recommended?

From the Guidelines

Combination therapy with Jardiance (empagliflozin) and metformin is recommended for patients with type 2 diabetes who require additional glucose control beyond what a single medication can provide, as it can provide better glycemic control and has complementary effects on heart and kidney protection. This dual therapy approach is effective because these medications work through different mechanisms, with metformin reducing glucose production in the liver and improving insulin sensitivity, and Jardiance helping the kidneys remove excess glucose through urine 1. The most recent guidelines suggest that metformin is a commonly used medication that historically has been the first-line treatment for type 2 diabetes, and it is effective and safe, inexpensive, and widely available, and reduces risks of microvascular complications, cardiovascular events, and death 1.

When A1C is ≥1.5% above the individualized glycemic goal, many individuals will require dual-combination therapy or a more potent glucose-lowering agent to achieve and maintain their goal A1C level 1. The combination of Jardiance and metformin may provide better glycemic control than either medication alone, with complementary effects that can help achieve target blood glucose levels. Patients should be aware of potential side effects, including urinary tract infections and genital yeast infections from Jardiance, and gastrointestinal issues from metformin. Regular monitoring of kidney function is important when taking Jardiance, and the combination may need adjustment in patients with reduced kidney function.

Some key points to consider when using this combination therapy include:

• Typical dosing ranges from 5-25 mg daily for Jardiance and 500-2000 mg twice daily for metformin, though specific dosing should be determined by a healthcare provider based on individual factors 1.
• Metformin is available in an immediate-release form for twice-daily dosing or as an extended-release form that can be given once daily 1.
• The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration and/or using extended-release formulation 1.
• Jardiance has additional benefits for heart and kidney protection, and is recommended as part of the antihyperglycemic regimen for patients with type 2 diabetes who have established atherosclerotic cardiovascular disease 1.

From the FDA Drug Label

JARDIANCE has been studied as monotherapy and in combination with metformin, sulfonylurea, pioglitazone, linagliptin, and insulin. Add-On Combination Therapy with Metformin A total of 637 patients with type 2 diabetes participated in a double-blind, placebo-controlled study to evaluate the efficacy and safety of JARDIANCE in combination with metformin Initial Combination Therapy with Metformin A total of 1364 patients with type 2 diabetes participated in a double-blind, randomized, active-controlled study to evaluate the efficacy and safety of JARDIANCE in combination with metformin as initial therapy compared to the corresponding individual components

Duo therapy with JARDIANCE and metformin is recommended as it has been studied and shown to provide statistically significant reductions in HbA1c, FPG, and body weight compared with placebo 2. The combination of JARDIANCE and metformin has been evaluated in both add-on and initial combination therapy settings, demonstrating its efficacy and safety in patients with type 2 diabetes 2. Key benefits of this duo therapy include:

• Statistically significant reductions in HbA1c
• Reductions in FPG and body weight
• Efficacy and safety in patients with type 2 diabetes, including those with mild or moderate renal impairment.

From the Research

Duo Therapy with Jardiance and Metformin

• The combination of Jardiance (empagliflozin) and metformin for the treatment of type 2 diabetes has been studied in various clinical trials 3, 4.
• According to a study published in 2016, metformin monotherapy remains the treatment of choice for most patients with type 2 diabetes, and empagliflozin can be used as an add-on therapy for patients with significant cardiovascular risk factors 3.
• A 2018 review of empagliflozin found that it is an effective and generally well-tolerated antihyperglycemic agent that can be used as monotherapy or in combination with other antidiabetic agents, including metformin 4.
• The 2020 study on advances in type 2 diabetes therapy recommends SGLT2 inhibitors, such as empagliflozin, for people with atherosclerotic cardiovascular disease, heart failure, or kidney disease, which can be used in combination with metformin 5.
• However, the more recent studies 6, 7 focus on the cardiovascular and kidney outcomes of GLP-1 receptor agonists, rather than the specific combination of Jardiance and metformin.

Recommendations

• Based on the available evidence, the combination of Jardiance and metformin may be recommended for patients with type 2 diabetes and significant cardiovascular risk factors 3, 4.
• However, the decision to use this combination therapy should be made on a case-by-case basis, taking into account the individual patient's needs and medical history.
• It is essential to consider the potential benefits and risks of the combination therapy, including the increased risk of genital infections, kidney failure, and diabetic ketoacidosis associated with empagliflozin 3, 4.