Optimal Add-On Therapy for Uncontrolled Type 2 Diabetes with Elevated LFTs
Direct Recommendation
Add an SGLT-2 inhibitor (empagliflozin 10-25 mg daily or dapagliflozin 5-10 mg daily) immediately to the current regimen of Lantus and glipizide, and simultaneously increase the Lantus dose from 10 units to at least 20 units daily with titration by 2 units every 3 days until fasting glucose reaches 80-130 mg/dL. 1, 2
Critical First Steps
Address Insulin Non-Adherence and Inadequate Dosing
The current Lantus dose of 10 units is grossly inadequate for an A1C of 10.7%, which represents severe hyperglycemia requiring immediate intensification. 3, 1
Increase basal insulin to 0.2 units/kg/day (approximately 15-20 units for a typical 69-year-old male) and titrate by 2 units every 3 days until fasting glucose consistently reaches 80-130 mg/dL, with a maximum dose of 0.5 units/kg/day. 1
Address adherence barriers directly: Assess for cost concerns, injection technique problems, fear of hypoglycemia, or cognitive barriers that may explain inconsistent insulin use. 1
Discontinue Glipizide When Intensifying Insulin
Discontinue glipizide once basal insulin exceeds 20 units daily or when moving to more complex insulin regimens, as the combination significantly increases hypoglycemia risk without substantial additional glycemic benefit. 1
The sulfonylurea poses unnecessary hypoglycemia risk in a 69-year-old patient, particularly with irregular meal patterns or renal impairment. 4
Add SGLT-2 Inhibitor as Primary Add-On Therapy
Why SGLT-2 Inhibitor is the Optimal Choice
SGLT-2 inhibitors reduce all-cause mortality, major adverse cardiovascular events, and hospitalization for heart failure in patients with type 2 diabetes, making them the preferred add-on agent. 3
Empagliflozin added to insulin (with or without other agents) reduces HbA1c by 0.5-0.7% at 18 weeks and maintains this reduction through 78 weeks, with additional benefits of 2-3 kg weight loss and blood pressure reduction. 2
SGLT-2 inhibitors are safe in patients with liver disease, unlike metformin which is contraindicated with elevated LFTs. 5, 6
The mechanism is insulin-independent, making SGLT-2 inhibitors effective regardless of β-cell function or insulin resistance severity. 5, 7
Specific SGLT-2 Inhibitor Selection
Start empagliflozin 10 mg daily, increasing to 25 mg daily after 4 weeks if tolerated, as this provides the greatest cardiovascular mortality reduction (38% relative risk reduction) and all-cause mortality reduction (32%). 7, 2
Alternative: dapagliflozin 5 mg daily, increasing to 10 mg daily, which provides similar glycemic efficacy with proven cardiovascular benefits. 8
Check eGFR before initiating: SGLT-2 inhibitors require eGFR ≥30 mL/min/1.73 m² for empagliflozin, though glycemic efficacy diminishes below 60 mL/min/1.73 m². 2, 5
Why Not GLP-1 Receptor Agonist?
GLP-1 receptor agonists are the alternative preferred injectable add-on therapy with similar cardiovascular benefits (reduction in all-cause mortality, MACE, and stroke). 3
However, SGLT-2 inhibitors are preferred in this specific case because they work synergistically with insulin without requiring additional injections, have proven efficacy when added to insulin therapy, and avoid the gastrointestinal side effects common with GLP-1 agonists. 3, 2
If SGLT-2 inhibitors are contraindicated or not tolerated, add a GLP-1 receptor agonist (semaglutide 0.25 mg weekly titrating to 1 mg weekly, or dulaglutide 1.5 mg weekly) as the next best option. 3, 4
Expected Outcomes and Monitoring
Anticipated HbA1c Reduction
Expected HbA1c reduction: 2.0-2.5% total (1.5% from insulin intensification + 0.5-0.7% from SGLT-2 inhibitor addition), bringing A1C from 10.7% to approximately 8.2-8.7% within 3 months. 1, 2
If HbA1c remains >8% after 3 months, add prandial insulin at the largest meal starting with 4 units or 10% of basal insulin dose. 1
Monitoring Requirements
Check fasting blood glucose daily during insulin titration to guide dose adjustments and prevent hypoglycemia. 1
Reassess HbA1c in 3 months to evaluate treatment response and determine if further intensification is needed. 1, 4
Monitor for SGLT-2 inhibitor-specific adverse effects: genital mycotic infections (10-15% incidence), urinary tract infections, and volume depletion leading to orthostatic hypotension, particularly in elderly patients. 5, 6, 7
Educate on diabetic ketoacidosis warning signs (nausea, vomiting, abdominal pain, fatigue) as SGLT-2 inhibitors carry a small risk of euglycemic DKA, especially during illness or fasting. 5
Critical Caveats and Pitfalls
Assess for Cardiovascular Disease
Screen for established atherosclerotic cardiovascular disease (prior MI, stroke, peripheral artery disease) as this would further support SGLT-2 inhibitor or GLP-1 agonist selection. 3
Screen for heart failure symptoms or history, as SGLT-2 inhibitors provide a 36% reduction in heart failure hospitalization. 7, 3
Renal Function Assessment
Check eGFR and adjust metformin discontinuation accordingly: metformin requires dose reduction if eGFR 30-45 mL/min/1.73 m² and discontinuation if eGFR <30 mL/min/1.73 m². 3
Verify the reason for elevated LFTs to ensure metformin discontinuation is truly necessary, as non-alcoholic fatty liver disease alone is not a contraindication to metformin. 3
Avoid Common Errors
Do not target HbA1c <6.5% in a 69-year-old patient, as this increases hypoglycemia risk without cardiovascular benefits. 3, 4
Do not continue glipizide once insulin exceeds 20 units daily, as this combination dramatically increases severe hypoglycemia risk. 1
Do not add DPP-4 inhibitors, as they provide no mortality or cardiovascular benefit and are inferior to SGLT-2 inhibitors and GLP-1 agonists. 3