What are the considerations for adding Rybelsus (semaglutide) to a 55-year-old male's regimen of metformin (2000 mg) and glipizide (10 mg) for a hemoglobin A1c (HbA1c) level of 8.5%?

From the Guidelines

Adding Rybelsus (semaglutide) to the current regimen of metformin 2000 mg and glipizide 10 mg is a suitable option for this 55-year-old male with an A1C of 8.5%. According to the 2025 standards of care in diabetes 1, when A1C is ≥1.5% above the individualized glycemic goal, dual-combination therapy or a more potent glucose-lowering agent may be necessary to achieve and maintain the goal A1C level. Rybelsus, a GLP-1 receptor agonist, can be initiated at 3 mg once daily for 30 days, then increased to 7 mg once daily, and if needed, to the maximum dose of 14 mg once daily.

Key Considerations

• Rybelsus should be taken on an empty stomach with no more than 4 ounces of plain water, at least 30 minutes before the first food, beverage, or other oral medications of the day 1.
• As a GLP-1 receptor agonist, Rybelsus works by increasing insulin secretion when glucose levels are high, reducing glucagon secretion, slowing gastric emptying, and promoting satiety, which often leads to weight loss.
• Common side effects include nausea, vomiting, diarrhea, abdominal pain, and decreased appetite.
• When adding Rybelsus, consider reducing the glipizide dose to minimize hypoglycemia risk, and monitor the patient's kidney function as both metformin and Rybelsus require dose adjustments in renal impairment 1.

Monitoring and Adjustments

• Regularly monitor the patient's A1C levels, kidney function, and potential side effects.
• Adjust the glipizide dose as needed to minimize hypoglycemia risk.
• Consider periodic testing of vitamin B12 levels due to the potential increased risk of vitamin B12 deficiency associated with metformin use 1.

From the FDA Drug Label

Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin [see Warnings and Precautions (5.5)] Table 2. Hypoglycemia Adverse Reactions in Placebo-Controlled Trials in Patients with Type 2 Diabetes Mellitus Add-on to Basal Insulin with or without Metformin (30 weeks) N=132 N=132 N=131 Severe† 0% 0% 1.5% Documented symptomatic (≤70 mg/dL glucose threshold) 15.2% 16.7% 29. 8%

The patient is on metformin and glipizide, which is an insulin secretagogue. Adding Rybelsus (semaglutide) may increase the risk of hypoglycemia.

• Key points to consider:
  • The patient's current A1c is 8.5%, which is above the target range.
  • Glipizide can increase the risk of hypoglycemia when used with other diabetes medications.
  • Semaglutide can also increase the risk of hypoglycemia, especially when used with insulin secretagogues like glipizide.
• Clinical decision: When adding Rybelsus to the patient's current regimen, it is essential to monitor blood glucose levels closely to minimize the risk of hypoglycemia. The patient should be educated on the signs and symptoms of hypoglycemia and how to manage it. 2

From the Research

Treatment Options for Type 2 Diabetes

The patient is currently on metformin 2000mg and glipizide, and the goal is to add Rybelsus (a glucagon-like peptide-1 receptor agonist) to achieve an A1c of 8.5.

• The current treatment regimen includes metformin, which is a well-established first-line agent for type 2 diabetes management, as it reduces glucose production in the liver, decreases insulin resistance, and increases insulin sensitivity 3.
• However, for patients who would benefit from cardio-renal protection, newer agents such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists are favored as first-line therapy 3.
• The addition of Rybelsus to the current regimen may be beneficial, as glucagon-like peptide-1 receptor agonists have been shown to be effective in reducing HbA1c levels, with a reduction of 1.0% compared to placebo when added to metformin and sulphonylureas 4.

Considerations for Adding Rybelsus

• When considering the addition of a third-line agent to metformin and sulphonylureas, Rybelsus (a glucagon-like peptide-1 receptor agonist) has been shown to be effective in reducing HbA1c levels, with a similar reduction to sodium-glucose co-transporter-2 inhibitors 4.
• The choice of third-line agent should be individualized based on cost, personal preferences, and overall treatment goals, taking into account the wishes and priorities of the patient 5.
• It is essential to weigh the benefits and drawbacks of each treatment option, including the potential risks of hypoglycemia, weight gain, and other adverse effects 6, 4.

Potential Risks and Benefits

• The combination of metformin and Rybelsus may increase the risk of metabolic acidosis, including lactic acidosis and euglycemic diabetic ketoacidosis 7.
• However, the benefits of adding Rybelsus to the current regimen, including improved glycemic control and potential weight loss, may outweigh the risks for some patients 4.
• Care should be taken to monitor the patient's response to the new treatment regimen and adjust as necessary to minimize the risk of adverse effects 6, 4.