What is a reasonable third oral antidiabetic medication to add to a regimen for a patient with hyperglycemia (elevated blood glucose), already taking metformin and dapagliflozin, who refuses insulin therapy and has a hemoglobin A1c (HbA1c) level indicating poor glucose control?

From the Guidelines

A reasonable third oral diabetes medication to add to this patient's regimen would be a GLP-1 receptor agonist like semaglutide (Rybelsus) or a DPP-4 inhibitor such as sitagliptin (Januvia). Given the patient's poor glucose control despite maximum doses of metformin and dapagliflozin, and their refusal of insulin therapy, an oral GLP-1 receptor agonist would likely provide the most robust additional glycemic control 1.

Key Considerations

• The patient's current regimen includes metformin and dapagliflozin, which work by reducing hepatic glucose production and increasing urinary glucose excretion, respectively.
• The addition of a GLP-1 receptor agonist or a DPP-4 inhibitor would complement these actions by increasing insulin secretion in response to meals and reducing glucagon production.
• Oral semaglutide could be started at 3 mg daily for one month, then increased to 7 mg daily, and potentially to 14 mg daily if needed and tolerated, as per the dosing guidelines 1.
• Alternatively, sitagliptin 100 mg once daily would be a more modest but better-tolerated option, with a lower risk of gastrointestinal side effects compared to GLP-1 receptor agonists 1.

Potential Benefits and Risks

• The patient should understand that with such poor glycemic control, a triple oral regimen may still be insufficient, and insulin might eventually become necessary to prevent complications of diabetes, including worsening foot infections.
• The choice of medication should be based on the patient's clinical characteristics, preferences, and potential side effects, as well as the medication's efficacy, safety, and cost 1.

Monitoring and Follow-up

• Regular monitoring of the patient's blood glucose levels, HbA1c, and other relevant clinical parameters is crucial to assess the effectiveness of the new medication and adjust the treatment plan as needed.
• The patient should be educated on the importance of adherence to the medication regimen, lifestyle modifications, and regular follow-up appointments to optimize their diabetes management.

From the FDA Drug Label

Add-On Combination Therapy with a Sulfonylurea A total of 597 adult patients with type 2 diabetes mellitus and inadequate glycemic control (HbA1c ≥7% and ≤10%) were randomized in this 24-week, placebo-controlled trial to evaluate dapagliflozin in combination with glimepiride (a sulfonylurea) In combination with glimepiride, dapagliflozin 10 mg provided statistically significant improvement in HbA1c, FPG, and 2-hour PPG, and statistically significant reduction in body weight compared with placebo plus glimepiride at Week 24

A reasonable third oral antidiabetic medication to add to a regimen for a patient with hyperglycemia, already taking metformin and dapagliflozin, who refuses insulin therapy and has a hemoglobin A1c (HbA1c) level indicating poor glucose control is a sulfonylurea, such as glipizide or glimepiride 2.

• Key benefits of adding a sulfonylurea include:
  • Improvement in HbA1c
  • Reduction in body weight
  • Improvement in FPG and 2-hour PPG
• Important consideration: Down-titration of the sulfonylurea may be necessary to prevent hypoglycemia.

From the Research

Reasonable Third Oral Antidiabetic Medication

To determine a reasonable third oral antidiabetic medication for a patient with hyperglycemia, already taking metformin and dapagliflozin, who refuses insulin therapy and has a hemoglobin A1c (HbA1c) level indicating poor glucose control, several factors must be considered.

• The patient's current regimen includes metformin and dapagliflozin, which are commonly used in combination for the treatment of type 2 diabetes mellitus 3.
• The addition of a third oral antidiabetic medication should be based on the patient's clinical characteristics, efficacy, side effects, mechanism of action, risk of hypoglycemia, effect on body weight, patient preference, and combined comorbidity 4.
• Pioglitazone has been shown to be an effective and safe addition to metformin and dapagliflozin in patients with inadequately controlled type 2 diabetes, with significant reductions in HbA1c levels and a favorable safety profile 5.
• Other options, such as thiazolidinediones, exenatide, and dipeptidyl peptidase-4 inhibitors, may also be considered, but the choice of medication should be individualized based on the patient's specific needs and characteristics 6.

Key Considerations

When selecting a third oral antidiabetic medication, the following key considerations should be taken into account:

• Efficacy in reducing HbA1c levels
• Safety profile, including risk of hypoglycemia and other adverse events
• Effect on body weight and lipid metabolism
• Patient preference and tolerability
• Combined comorbidity and potential interactions with other medications

Potential Options

Based on the available evidence, potential options for a third oral antidiabetic medication include:

• Pioglitazone, which has been shown to be effective and safe in combination with metformin and dapagliflozin 5
• Other thiazolidinediones, such as rosiglitazone, which may have similar efficacy and safety profiles 7
• Exenatide and other dipeptidyl peptidase-4 inhibitors, which may offer additional benefits in terms of weight loss and cardiovascular risk reduction 6