What is the best course of action for a patient with uncontrolled diabetes, with a Hemoglobin A1c (HbA1c) level of 8.9%, who is adherent to Metformin (Metformin) 1000 milligrams (mg) orally (PO) twice a day (BID) with meals, but discontinued Jardiance (Empagliflozin) 10 mg PO daily due to increased urinary symptoms and perceived lack of efficacy, with home glucose monitoring results showing hyperglycemia, including fasting levels of 140-160 milligrams per deciliter (mg/dL) and postprandial levels in the 200's, with occasional severe hyperglycemia in the 300's-400's?

From the Guidelines

The patient's diabetes is poorly controlled with an HbA1c of 8.9% and concerning blood glucose readings, and I strongly recommend restarting Jardiance 10 mg daily immediately while continuing Metformin 1000 mg twice daily with meals. The patient should adhere to both medications as prescribed, as they work through different mechanisms to lower blood sugar. Metformin decreases glucose production by the liver and improves insulin sensitivity, while Jardiance helps the kidneys remove excess glucose through urine 1. The increased urinary symptoms experienced were likely a normal side effect of Jardiance, which works by increasing glucose excretion in urine. This is actually a sign the medication was working, not a reason to discontinue it. With blood sugars frequently in the 200-400 mg/dL range and an elevated HbA1c, the patient is at significant risk for diabetes complications including kidney disease, nerve damage, and cardiovascular problems.

Some key points to consider in the management of this patient's diabetes include:

• The importance of metformin as a first-line treatment for type 2 diabetes, due to its efficacy, safety, and low cost 1
• The potential benefits of combination therapy, including the use of SGLT2 inhibitors like Jardiance, in achieving and maintaining glycemic goals 1
• The need for regular blood glucose monitoring and documentation of readings to share with the healthcare team
• The potential risks and side effects of diabetes medications, including gastrointestinal intolerance with metformin and increased urinary symptoms with Jardiance 1

If blood sugars remain elevated after restarting both medications for 2-4 weeks, the patient should contact their healthcare provider as insulin therapy or additional medications may be necessary. Regular blood glucose monitoring should continue, with documentation of readings to share with the healthcare team. According to the most recent guidelines, 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.

From the FDA Drug Label

In patients with type 2 diabetes, treatment with JARDIANCE reduced hemoglobin A1c (HbA1c), compared to placebo The reduction in HbA1c for JARDIANCE compared with placebo was observed across subgroups including gender, race, geographic region, baseline BMI and duration of disease. 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 At Week 24, treatment with JARDIANCE 10 mg or 25 mg daily provided statistically significant reductions in HbA1c (p-value <0. 0001), FPG, and body weight compared with placebo

The patient's HbA1c is 8.9, and she is taking Metformin 1000 mg PO BID and Jardiance 10 mg PO daily. The patient stopped taking Jardiance after a month, but the data suggests that Jardiance in combination with Metformin can provide statistically significant reductions in HbA1c.

• The patient should be advised to restart Jardiance as prescribed to potentially improve her glycemic control.
• The patient's home glucose monitoring shows elevated blood glucose levels, which may be improved with consistent use of Jardiance and Metformin.
• The patient's urinary symptoms should be monitored and addressed as needed. 2

From the Research

Patient's Current Condition

• The patient has a HbA1c level of 8.9, indicating poor glycemic control.
• The patient is taking Metformin 1000 mg PO BID daily with meals and was prescribed Jardiance 10 mg PO daily, but stopped taking Jardiance after a month due to increased urinary symptoms.
• The patient's blood glucose levels are high, with fasting levels ranging from 140-160 and post-prandial levels in the 200's, with occasional levels in the 300's-400's.
• The patient denies any recent hypoglycemic episodes.

Barriers to Glycemic Control

• Patient nonadherence to treatment is a significant barrier to glycemic control, as seen in this patient who stopped taking Jardiance due to side effects 3.
• Treatment side effects, such as increased urinary symptoms, can also hinder glycemic control 3.
• Complex treatment regimens and poor patient education can also contribute to poor glycemic control 3.

Comparison of Medications

• Studies have compared the efficacy of different medications, including Empagliflozin (Jardiance) and Sitagliptin, when combined with Metformin, in patients with type 2 diabetes 4, 5.
• One study found that the combination of Empagliflozin and Metformin was superior to the combination of Sitagliptin and Metformin for maintaining glycemic control 5.
• Another study found that Empagliflozin provided sustained glycemic and weight control and was well tolerated with a low risk of hypoglycemia in patients with type 2 diabetes 6.

Factors Affecting Glycemic Control

• Factors affecting glycemic control can be stratified into four categories: personal or body-related, clinical, medication-related, and behavioral factors 7.
• The patient's decision to stop taking Jardiance due to side effects is an example of a medication-related factor affecting glycemic control.
• The patient's high blood glucose levels and poor glycemic control are likely due to a combination of these factors.