What is the optimal strategy to lower hemoglobin A1c (HbA1c) in a 71-year-old male with hyperglycemia, currently taking metformin (Metformin) 1000 mg twice daily and Jardiance (Empagliflozin) 25 mg daily, without increasing the risk of hypoglycemic episodes?

From the Guidelines

The best approach to lower the A1c of this 71-year-old male without risking hypoglycemic episodes would be to add a GLP-1 receptor agonist, such as semaglutide (Ozempic), to his current regimen of metformin 1000 mg twice daily and Jorian 25 mg daily. This recommendation is based on the most recent and highest quality study available, which suggests that the addition of a GLP-1 receptor agonist to metformin can result in a 1 to 2% lowering of A1c 1. The patient's current regimen already includes metformin, which is a commonly used and effective medication for type 2 diabetes, and Jorian, which is likely an SGLT-2 inhibitor, given the context of the question and the provided evidence. The addition of a GLP-1 agonist would complement these medications by working through a different mechanism, enhancing glucose-dependent insulin secretion, suppressing glucagon, and slowing gastric emptying. Some key points to consider when adding a GLP-1 receptor agonist include:

• Starting with a low dose, such as 0.25 mg weekly, and gradually increasing to 0.5 mg weekly to minimize gastrointestinal side effects
• Regular monitoring of kidney function, as GLP-1 receptor agonists may affect kidney function
• Counseling the patient about potential gastrointestinal side effects, which typically improve with continued use
• Considering the patient's difficulty maintaining weight, the weight loss or weight neutrality associated with GLP-1 receptor agonists is an added benefit. It is also important to note that the patient's A1c level is only slightly above the individualized glycemic goal, and the addition of a GLP-1 receptor agonist may be sufficient to achieve the desired A1c level without increasing the risk of hypoglycemia 1.

From the FDA Drug Label

At Week 24, initial therapy of JARDIANCE in combination with metformin provided statistically significant reductions in HbA1c (p-value <0. 01) compared to the individual components A total of 666 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 plus a sulfonylurea 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 best way to lower the patient's A1c without risking hypoglycemic episodes is to continue the current treatment regimen of metformin 1000 mg twice daily and JARDIANCE 25 mg daily, as the patient is already on this regimen and it has been shown to be effective in reducing HbA1c levels 2.

• Monitor the patient's glucose levels to ensure that they are not experiencing hypoglycemic episodes.
• Adjust the treatment regimen only if necessary, based on the patient's response to the current treatment and their overall health status. It is also important to note that the patient's healthy BMI and difficulty maintaining weight should be taken into consideration when making any changes to their treatment regimen.

From the Research

Patient Profile

• 71-year-old male with type 2 diabetes
• A1c level: 7.4%
• Fasting glucose: 79-130 mg/dL
• Current medications: metformin 1000 mg twice daily, Jorian 25 mg daily
• Healthy BMI, difficulty maintaining weight

Treatment Options to Lower A1c

• Consider adding a GLP-1 receptor agonist or SGLT2 inhibitor to the patient's current medication regimen, as these classes of drugs have been shown to have beneficial effects on glycemic control, weight, and cardiovascular risk factors 3, 4, 5
• GLP-1 receptor agonists may be particularly beneficial for patients with established or high-risk cardiovascular disease, while SGLT2 inhibitors may be more effective for patients with heart failure or chronic kidney disease 3, 5
• Long-acting GLP-1 receptor agonists, including both injectable and oral formulations, have been shown to reduce the incidence of major adverse cardiovascular events, hospitalization for heart failure, and kidney events, as well as all-cause mortality in patients with type 2 diabetes 6

Considerations for Treatment Intensification

• When intensifying treatment, consider adding a new medication rather than maximizing the dose of the current medication, as this approach may be associated with a slightly larger reduction in systolic blood pressure, although it may also be less sustainable 7
• The choice of treatment intensification strategy should be individualized based on the patient's specific needs and risk profile

Potential Benefits and Risks

• The addition of a GLP-1 receptor agonist or SGLT2 inhibitor to the patient's current medication regimen may provide beneficial effects on glycemic control, weight, and cardiovascular risk factors, with a low risk of severe hypoglycemia or other adverse events 3, 4, 5, 6
• However, the patient's difficulty maintaining weight should be taken into account when selecting a treatment option, as some medications may have a greater impact on weight loss or gain 3, 4