What is the best course of action for a patient with uncontrolled diabetes, hypertension, fatty liver, and hyperlipidemia, on Tresiba (insulin degludec) 40 units subcutaneously (SQ) twice a day, Novolog (insulin aspart) U-100 16 units three times a day (TID) with a sliding scale, and Xigduo XR (dapagliflozin and metformin) 10-1000 once a day, with an increased Hemoglobin A1c (HbA1c) from 10.7% to 12.7% and mildly impaired renal function?

Management of Uncontrolled Type 2 Diabetes with HbA1c 12.7%

This patient requires immediate and aggressive insulin intensification with optimization of the basal insulin regimen and addition of a GLP-1 receptor agonist, while correcting the inappropriate twice-daily dosing of Tresiba. 1, 2

Critical Error in Current Regimen

The patient is receiving Tresiba (insulin degludec) 40 units twice daily, which is incorrect dosing. 3

• Tresiba is a once-daily basal insulin with a half-life exceeding 25 hours and should never be dosed twice daily 3
• The FDA label explicitly states: "In adults, inject Insulin Degludec subcutaneously once-daily at any time of day" 3
• This dosing error may be contributing to unpredictable glycemic control and potential hypoglycemia risk 3

Immediate Treatment Plan

Step 1: Correct the Basal Insulin Regimen

Consolidate Tresiba to 80 units once daily (the current total daily dose). 3

• Start with the combined dose of 80 units once daily, administered at the same time each day 3
• Titrate by 2-4 units every 3-4 days based on fasting glucose, targeting 80-130 mg/dL 1, 2
• The recommended interval between dose increases is 3-4 days per FDA labeling 3
• Monitor closely during the transition, as twice-daily dosing may have created overlapping insulin action 3

Step 2: Optimize Prandial Insulin Coverage

The current Novolog dose of 16 units TID is likely insufficient given the HbA1c of 12.7%. 2, 4

• Increase prandial insulin by 1-2 units or 10-15% twice weekly based on 2-hour postprandial glucose readings 2, 4
• Target postprandial glucose <180 mg/dL 2
• Consider increasing to 20 units TID initially, then titrate based on response 4

Step 3: Add a GLP-1 Receptor Agonist

Adding a GLP-1 receptor agonist is strongly recommended for this patient with HbA1c 12.7%. 1, 2, 5

• GLP-1 receptor agonists can provide HbA1c reduction of 2-2.5% when added to insulin therapy 2, 5
• They offer weight loss benefits (critical given fatty liver and hyperlipidemia) rather than the weight gain associated with insulin intensification alone 1, 5
• Studies show GLP-1 receptor agonists are superior or equivalent to insulin intensification at baseline HbA1c >10%, with mean reductions of 3.1% from HbA1c of 10.6% 5
• The eGFR of 84 allows safe use of all GLP-1 receptor agonists 2

Step 4: Continue Xigduo XR (Dapagliflozin-Metformin)

Maintain the current Xigduo XR 10-1000 mg once daily. 1, 2, 6

• Metformin remains the foundation of therapy and should be continued unless contraindicated 1, 2
• The eGFR of 84 is well above the threshold for metformin continuation (GFR >30 mL/min) 1
• Dapagliflozin provides complementary glucose-lowering (HbA1c reduction of 0.5-0.7%), cardiovascular benefits, and weight loss 6
• SGLT2 inhibitors reduce total insulin requirements when used in combination 2
• Consider increasing to Xigduo XR 10-2000 mg if gastrointestinal tolerance permits, as the patient is on a submaximal metformin dose 1

Monitoring and Follow-up

Reassess HbA1c in 3 months to determine if additional intensification is needed. 1

• The ADA/EASD consensus specifically proposes that if glycemic targets are not achieved within 3-6 months, treatment should be changed or intensified 1
• Increase frequency of blood glucose monitoring during the regimen transition 3
• Monitor for hypoglycemia, particularly 2-4 hours after prandial insulin doses 4
• Check renal function periodically, as both metformin and dapagliflozin require adjustment with declining kidney function 2

Critical Pitfalls to Avoid

Do not delay insulin intensification while trying additional oral agents at this HbA1c level. 1, 2

• Prolonged severe hyperglycemia (HbA1c >9% for months) increases complication risk and should be specifically avoided 1, 2
• Most oral agents reduce HbA1c by <1%, making them insufficient as monotherapy at baseline HbA1c of 12.7% 1

Do not rely on sliding scale insulin alone without optimizing basal insulin first. 4

• Sliding scale insulin is strongly discouraged and ineffective for long-term glycemic management 4
• It treats hyperglycemia reactively rather than preventing it 4

Do not continue the twice-daily Tresiba dosing. 3

• This represents a fundamental medication error that must be corrected immediately 3
• Twice-daily dosing of a once-daily basal insulin creates unpredictable pharmacokinetics 3

Special Considerations for Comorbidities

The presence of fatty liver disease does not contraindicate any of the recommended therapies. 7

• Metformin is recommended as first-line therapy for patients with diabetes and chronic liver disease 7
• GLP-1 receptor agonists and SGLT2 inhibitors exhibit positive effects on weight and hepatic steatosis 7
• Pioglitazone may be beneficial for fatty liver but is not prioritized given the need for aggressive glycemic control 7

The patient's hypertension and hyperlipidemia increase cardiovascular risk, making GLP-1 receptor agonist addition even more important. 1

• Select a GLP-1 receptor agonist with proven cardiovascular benefits (liraglutide, semaglutide, or dulaglutide) 1
• These agents provide cardiovascular protection beyond glucose lowering 1