From the Guidelines
For a patient with an HbA1c greater than 14% who is already on a maximum dose of metformin, the recommended next step is to initiate insulin therapy, as it is the most effective way to rapidly improve glycemic control in severely uncontrolled diabetes, as suggested by the most recent guidelines 1.
Rationale for Insulin Therapy
The choice of insulin therapy is based on its potent glucose-lowering effect and ability to rapidly improve glycemic control. According to the standards of care in diabetes-2025, insulin has the advantage of being effective where other agents are not and should be considered as part of any combination regimen when hyperglycemia is severe 1.
Initiating Insulin Therapy
Start with basal insulin, such as insulin glargine or insulin detemir, at an initial dose of 0.1-0.2 units/kg/day, typically given once daily. Adjust the dose every 3-7 days based on fasting blood glucose levels, aiming for a target of 80-130 mg/dL. If needed, add prandial insulin before meals, starting with 4 units or 10% of the basal dose at each meal, and titrate as necessary.
Alternative Options
Alternatively, if the patient is averse to injections or has a low risk of hypoglycemia, consider adding a GLP-1 receptor agonist like semaglutide (start with 0.25 mg subcutaneously once weekly, increasing to 0.5 mg after 4 weeks, and potentially to 1 mg if needed) or liraglutide (start with 0.6 mg subcutaneously daily, increase to 1.2 mg after a week, and potentially to 1.8 mg if needed) 1.
Key Considerations
- Close monitoring of blood glucose levels and regular follow-up are essential during treatment intensification.
- The choice of medication added to metformin is based on the clinical characteristics of the patient and their preferences, including the presence of established ASCVD or indicators of high ASCVD risk, other comorbidities, and risk for specific adverse drug effects, as well as safety, tolerability, and cost 1.
- GLP-1 receptor agonists offer significant HbA1c reduction with the added benefits of weight loss and cardiovascular protection, and work well in combination with metformin 1.
From the Research
Antidiabetic Agents for Severe Hyperglycemia
In patients with severe hyperglycemia (HbA1c > 14) who are on a maximum dose of Metformin, several antidiabetic agents can be considered as add-on therapy.
- Empagliflozin: Studies have shown that empagliflozin can be effective in reducing HbA1c levels in patients with type 2 diabetes who are already on metformin therapy 2, 3, 4.
- GLP-1 Receptor Agonists: GLP-1 receptor agonists, such as exenatide and liraglutide, have been shown to be effective in reducing HbA1c levels and may be considered as an alternative to insulin therapy 5, 6.
- Insulin: Insulin therapy may also be considered for patients with severe hyperglycemia, especially if other treatments are not effective or if the patient has symptoms of hyperglycemia 5.
Considerations for Treatment Selection
When selecting an antidiabetic agent for a patient with severe hyperglycemia, several factors should be considered, including:
- Efficacy in reducing HbA1c levels
- Safety profile, including risk of hypoglycemia and other adverse events
- Potential for weight loss or gain
- Impact on blood pressure and lipid profile
- Patient preferences and lifestyle considerations
Empagliflozin as Add-on Therapy
Empagliflozin has been shown to be effective in reducing HbA1c levels when used as add-on therapy to metformin 2, 3, 4. The recommended dose of empagliflozin is 10-25 mg once daily.