What is the recommended next step in a 55-year-old patient with severe hyperglycemia (elevated blood glucose) on metformin (Metformin) 1000 mg twice a day (BID) and glipizide (Glipizide) 60 mg BID, with previous intolerance to Ozempic (Semaglutide) and Invokana (Canagliflozin)?

From the Guidelines

The recommended next step for this 55-year-old patient with severe hyperglycemia despite maximum doses of metformin and glipizide, and with previous intolerance to semaglutide and canagliflozin, would be to initiate insulin therapy. This approach is based on the most recent guidelines from the Diabetes Care journal, which suggest that insulin therapy should be considered when oral medications and non-insulin injectables have failed or are not tolerated, especially in patients with severe hyperglycemia 1. The patient's A1c level of 10.7 and recent random glucose level above 20 indicate severe hyperglycemia, which requires prompt treatment to prevent complications. According to the guidelines, insulin therapy is indicated for patients with blood glucose levels ≥300 mg/dL or A1C >10% 1. The patient should start with basal insulin, such as insulin glargine (Lantus) or insulin detemir (Levemir), at an initial dose of 0.1-0.2 units/kg/day, and adjust the dose based on fasting blood glucose readings. The patient should continue metformin but consider reducing or discontinuing glipizide to minimize hypoglycemia risk when starting insulin. Insulin therapy has been shown to be effective in achieving glycemic control and reducing the risk of complications in patients with type 2 diabetes 1. The patient will need education on insulin administration, blood glucose monitoring, hypoglycemia recognition and management, and should follow up within 1-2 weeks of insulin initiation to assess response and make necessary adjustments. Key points to consider when initiating insulin therapy include:

• Starting with a low dose and gradually increasing as needed
• Monitoring blood glucose levels regularly to adjust the dose
• Educating the patient on insulin administration and hypoglycemia management
• Considering the patient's lifestyle and preferences when selecting an insulin regimen
• Regular follow-up to assess response and make necessary adjustments.

From the FDA Drug Label

Repaglinide tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The recommended starting dose for patients whose HbA1c is 8% or greater the starting dose is 1 or 2 mg orally before each meal.

The recommended next step in a 55-year-old patient with severe hyperglycemia (elevated blood glucose) on metformin 1000 mg twice a day and glipizide 60 mg twice a day, with previous intolerance to Ozempic and Invokana, could be to consider adding repaglinide to their treatment regimen.

• The patient's HbA1c is 10.7, which is greater than 8%, so the starting dose of repaglinide would be 1 or 2 mg orally before each meal.
• It is essential to monitor the patient's blood glucose levels and adjust the dose of repaglinide as needed to achieve satisfactory glycemic control.
• The patient should be instructed to take repaglinide tablets within 30 minutes before meals and to skip the scheduled dose if they skip a meal to reduce the risk of hypoglycemia 2.

From the Research

Patient Profile

• Age: 55 years
• A1c: 10.7
• Current medication: Metformin 1000 mg BID, Glipizide 60 mg BID
• Previous intolerance: Ozempic (Semaglutide), Invokana (Canagliflozin)
• Recent random glucose: above 20

Treatment Options

• Considering the patient's previous intolerance to Ozempic and Invokana, alternative treatment options need to be explored 3
• Meglitinide analogues, such as repaglinide and nateglinide, may be considered as add-on therapy to metformin and glipizide, as they have been shown to improve glycemic control and reduce postprandial hyperglycemia 4, 5
• Other options, such as sulfonylureas, pioglitazone, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, and basal insulin, may also be considered as combination therapy with metformin 6

Glycemic Control

• The goal of treatment is to achieve individualized target glycosylated hemoglobin levels as near to normal as safely possible (i.e., <7%) and avoid hypoglycemia 6
• Early combination therapy with two or three classes of drugs may be warranted, as type 2 diabetes is a multi-causal disease and the various classes of drugs have distinct and synergistic modes of action 6
• The glycemic response to antihyperglycemic therapies has been shown to be similar across different therapeutic classes, with no significant differences noted in glucose-lowering effect after adjustment for baseline clinical characteristics 7

Next Steps

• Consider adding a meglitinide analogue, such as repaglinide or nateglinide, to the patient's current medication regimen to improve glycemic control and reduce postprandial hyperglycemia 4, 5
• Alternatively, other combination therapy options may be explored, taking into account the patient's previous intolerance to Ozempic and Invokana, and the need to achieve individualized target glycosylated hemoglobin levels 3, 6