What are the treatment guidelines for a patient with new onset diabetes and a hemoglobin A1c (HbA1c) level of 10.9, indicating severe hyperglycemia?

From the Guidelines

For a patient with new onset diabetes and an A1c of 10.9%, immediate treatment with both lifestyle modifications and medication, including metformin and a second agent such as a GLP-1 receptor agonist or an SGLT-2 inhibitor, is recommended. This approach is based on the most recent guidelines, including those from the American Diabetes Association, as outlined in the 2020 standards of medical care in diabetes 1. The high A1c level indicates significant hyperglycemia, suggesting a longer duration of undiagnosed diabetes and requiring prompt intervention to prevent complications.

Initial Treatment

• Start with metformin 500 mg once daily with a meal for 1 week, then increase to 500 mg twice daily if tolerated, with a target dose of 1000 mg twice daily, adjusted based on tolerance and kidney function.
• Initiate a second medication such as a GLP-1 receptor agonist (like semaglutide 0.25 mg weekly, titrated up to 1 mg weekly) or an SGLT-2 inhibitor (such as empagliflozin 10 mg daily), considering the patient's clinical characteristics and preferences, as suggested by the 2020 guidelines 1.

Lifestyle Modifications

• Include a reduced-calorie diet.
• Regular physical activity, aiming for 150 minutes weekly of moderate exercise.
• Blood glucose monitoring to assess treatment response and adjust the regimen as necessary.

Follow-Up and Adjustment

• The patient should aim for a target A1c of less than 7% for most adults.
• Follow-up in 2-3 months to assess treatment response and adjust the medication regimen if necessary, considering the addition of other agents or insulin therapy if glycemic targets are not met, as recommended by the American Diabetes Association standards 1.

This approach prioritizes the reduction of morbidity, mortality, and improvement of quality of life by aggressively managing hyperglycemia and addressing the pathophysiologic defects in type 2 diabetes, in line with the most recent and highest quality evidence available 1.

From the FDA Drug Label

For patients who had not been previously treated with antidiabetic medication (24%), mean values at screening were 10.1% for HbA1c and 238 mg/dL for FPG. At baseline, mean HbA1c was 10.2% and mean FPG was 243 mg/dL. Compared with placebo, treatment with ACTOS titrated to a final dose of 30 mg and 45 mg resulted in reductions from baseline in mean HbA1c of 2.3% and 2. 6% and mean FPG of 63 mg/dL and 95 mg/dL, respectively.

For patients who had been previously treated with antidiabetic medication (76%), this medication was discontinued at screening. Mean values at screening were 9.4% for HbA1c and 216 mg/dL for FPG. At baseline, mean HbA1c was 10. 7% and mean FPG was 290 mg/dL. Compared with placebo, treatment with ACTOS titrated to a final dose of 30 mg and 45 mg resulted in reductions from baseline in mean HbA1c of 1.3% and 1. 4% and mean FPG of 55 mg/dL and 60 mg/dL, respectively.

Treatment Guidelines for New Onset Diabetes with A1c 10.9:

• The patient's A1c level is 10.9, which is higher than the mean baseline values in the studies.
• Pioglitazone (ACTOS) can be considered as a treatment option, with a starting dose of 15-30 mg once daily.
• The dose can be titrated to 30 mg or 45 mg once daily based on the patient's response.
• Combination therapy with other antidiabetic agents such as sulfonylurea or metformin can also be considered if the patient is not adequately controlled on pioglitazone alone.
• The goal of treatment is to reduce the patient's A1c level to <7% and FPG to <130 mg/dL.
• Regular monitoring of the patient's A1c and FPG levels is necessary to adjust the treatment plan as needed 2, 2.

From the Research

Treatment Guidelines for New Onset Diabetes with A1c 10.9

• The American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive T2DM 2017 management algorithm recommends insulin for T2DM patients presenting with symptoms and an HbA1c >9.0% 3.
• The American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus statement recommends initial insulin therapy as an option when HbA1c ≥9%, and definite consideration with HbA1c ≥10-12% 3.
• Short-term intensive insulin (STII) therapy could be a preferred option for new onset Type 2 diabetes mellitus patients with HbA1c >9% 3.
• Insulin secretion at baseline is the strongest predictor of subjects who do not require insulin therapy, with a cut point of CPEP120 /CPEP0 of more than 1.7 predicting subjects who achieve the treatment target without insulin 4.

Comparison of Insulin Detemir and Insulin Glargine

• There is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia 5.
• Insulin detemir was associated with less weight gain, while insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions 5.
• A randomized crossover trial found that insulin detemir achieved similar efficacy to insulin glargine when given once daily in hospitalized patients with type 2 diabetes 6.

Comparative Effectiveness of Antihyperglycaemic Medications

• SGLT2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of major adverse cardiovascular events (MACE) compared to DPP-4 inhibitors and sulfonylureas 7.
• There was no statistically significant difference in risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists 7.
• DPP-4 inhibitors were associated with reduced risk of MACE compared to sulfonylureas 7.