Should a 71-year-old female with type 2 diabetes mellitus, currently on Jardiance (Empagliflozin) and Metformin, with persistently elevated Hemoglobin A1c (HbA1c), be treated with Linagliptin, considering the risk of hypoglycemia?

From the Guidelines

Adding linagliptin to your current regimen of Jardiance and metformin is a reasonable option to improve your glycemic control, as your A1c has remained at 8.1% for a year, and it has a low risk of causing hypoglycemia when added to this combination, as stated in the 2025 standards of care in diabetes 1. The standard dose of linagliptin would be 5 mg once daily, taken with or without food. This medication helps your body produce more insulin when blood sugar is high and reduces glucose production from the liver. Some key points to consider when adding linagliptin include:

• The risk of hypoglycemia is minimal because linagliptin's insulin-stimulating effect diminishes as blood glucose levels normalize 1.
• Common side effects may include upper respiratory infections or headache, but it's generally well-tolerated.
• You should continue monitoring your blood glucose regularly after starting this medication and report any unusual symptoms to your healthcare provider. Given your persistent elevated A1c despite dual therapy, adding this third medication aligns with standard diabetes treatment algorithms for improving glycemic control when current therapy isn't meeting targets, as outlined in the 2025 standards of care in diabetes 1. Additionally, the 2024 standards of care in diabetes for older adults suggest that for individuals with complex or intermediate health status, an A1c goal of <8.0% may be appropriate, and treatment plan simplification or deintensification may be considered in certain circumstances 1. However, in your case, since you are 71 years old with type 2 diabetes and an A1c of 8.1%, adding linagliptin to your current regimen is a reasonable option to improve your glycemic control, as it has a low risk of causing hypoglycemia and is generally well-tolerated.

From the FDA Drug Label

In combination with metformin, TRADJENTA provided statistically significant improvements in A1C, FPG, and 2-hour PPG compared with placebo A similar decrease in body weight was observed for both treatment groups Rescue glycemic therapy was used in 7.8% of patients treated with TRADJENTA 5 mg and in 18.9% of patients treated with placebo.

The addition of linagliptin to metformin and jardiance may provide statistically significant improvements in A1C.

• Key points:
  • The risk of hypoglycemia is not directly mentioned in the provided text as a significant concern when adding linagliptin to metformin.
  • Linagliptin has been shown to provide improvements in A1C when used in combination with metformin.
  • The decision to add linagliptin should be based on individual patient needs and medical history, considering the potential benefits and risks 2.
  • It is essential to monitor the patient's glycemic control and adjust the treatment plan as needed to minimize the risk of hypoglycemia or other adverse effects.

From the Research

Adding Linagliptin to Existing Treatment

• The decision to add linagliptin to the existing treatment of metformin and Jardiance (empagliflozin) for a patient with type 2 diabetes and an A1c level of 8.1% should be based on the potential benefits and risks of this addition.
• A study from 2020 3 found that early combination therapy with linagliptin and metformin improved glycemic control to HbA1c ≤6.5% without increasing hypoglycemia, suggesting that linagliptin could be a useful addition to the treatment regimen.

Risk of Hypoglycemia

• The risk of hypoglycemia is a concern when adding new medications to the treatment of type 2 diabetes.
• However, the study from 2020 3 found that hypoglycemia occurred in <3% of patients, with a comparable incidence between treatment groups, suggesting that the addition of linagliptin may not significantly increase the risk of hypoglycemia.
• Another study from 2019 4 found that patients with elevated glycated hemoglobin A1c seem to better tolerate hyperglycemia and large glucose fluctuations during critical illness, and that more liberal targets may decrease the occurrence of hypoglycemia in patients with diabetes with elevated glycated hemoglobin A1c.

Combination Therapy

• Combination therapy with multiple medications is a common approach to managing type 2 diabetes.
• A study from 2020 5 found that a triple fixed-dose combination of empagliflozin, linagliptin, and metformin was bioequivalent to the corresponding free combinations, and that this combination may improve glycemic control in adults with type 2 diabetes.
• Another study from 2021 6 reviewed head-to-head clinical studies of GLP-1 receptor agonists, including dulaglutide, exenatide, and liraglutide, and found that all GLP-1 RA agents are effective therapeutic options at reducing A1C, but that differences exist in terms of magnitude of effect on A1C and weight as well as frequency of adverse effects.

Setting HbA1c Targets

• The American Diabetes Association recommends an HbA1c target of <7% for most adults with type 2 diabetes, but individualized targets may be appropriate based on patient characteristics and preferences.
• A study from 2015 7 discussed the importance of setting individualized HbA1c targets, and found that both "a priori" and "a posteriori" approaches may be useful for physicians to make appropriate therapeutic decisions and for patients to adhere to the best possible treatment.