In a 123 kg adult male with type 2 diabetes on metformin 2 g daily, basal insulin glargine (Lantus) ~60 U daily, prandial insulin lispro (Fiasp) 45‑60 U split across meals, and persistent hyperglycemia, should I add the SGLT2 inhibitor empagliflozin (Jardiance) or a GLP‑1 receptor agonist?

Add a GLP-1 Receptor Agonist to Your Current Regimen

In this 123 kg adult male with type 2 diabetes on metformin, basal insulin glargine, and prandial insulin lispro with persistent hyperglycemia, you should add a GLP-1 receptor agonist rather than empagliflozin (Jardiance). 1, 2

Primary Rationale: Insulin Optimization and Weight Management

Your patient is already on substantial insulin therapy (basal ~60 U + prandial 45-60 U daily) with persistent hyperglycemia, indicating insulin resistance and likely overbasalization. GLP-1 receptor agonists are specifically recommended as the preferred injectable therapy before advancing to more complex insulin regimens or when basal insulin alone is insufficient. 1, 2

Key Clinical Advantages of GLP-1 in This Context:

• Reduces insulin requirements by 10-20% while improving glycemic control, addressing the likely insulin overbasalization in your patient 2, 3
• Produces substantial weight loss (mean 2.22 kg with traditional GLP-1 RAs, up to 8.47 kg with tirzepatide), critically important for this 123 kg patient 1, 2
• Minimal hypoglycemia risk when combined with insulin after appropriate dose reduction 1
• Reduces postprandial glucose excursions, which is particularly relevant given the persistent hyperglycemia despite prandial insulin coverage 4, 3

Specific GLP-1 Agent Selection

Choose semaglutide (Ozempic) 0.25 mg weekly initially, titrating to 1 mg weekly, or consider tirzepatide (Mounjaro) 2.5 mg weekly titrating to 10-15 mg weekly if greater weight loss and HbA1c reduction are priorities. 1, 2

• Semaglutide and tirzepatide demonstrate superior glycemic control and weight loss compared to other GLP-1 RAs 1, 2
• Weekly dosing improves adherence compared to daily agents 4
• Tirzepatide produces the most substantial weight loss (mean 8.47 kg) and HbA1c reduction among all glucose-lowering agents 1, 2

Critical Insulin Adjustment Protocol

When initiating the GLP-1 RA, immediately reduce basal insulin glargine by 20% and reduce prandial insulin lispro by 10-20% to prevent hypoglycemia. 2, 3

Signs of Insulin Overbasalization to Monitor:

• Basal insulin dose exceeding 0.5 units/kg/day (this patient at 123 kg should not exceed ~60 U, which he is already at) 2
• Significant bedtime-to-morning glucose differential 2
• Hypoglycemia occurrences 2
• High glycemic variability despite adequate basal coverage 2

Why Not SGLT2 Inhibitor (Jardiance) in This Case

While SGLT2 inhibitors have proven cardiovascular and renal benefits, they are less appropriate as the next step in this specific clinical scenario:

• SGLT2 inhibitors provide modest HbA1c reduction (typically 0.5-0.7%) compared to GLP-1 RAs (0.8-1.5% or more with tirzepatide) 1
• Weight loss with SGLT2 inhibitors is modest (mean 2.48 kg) compared to GLP-1 RAs, particularly important for this 123 kg patient 1
• SGLT2 inhibitors do not address insulin resistance or reduce insulin requirements as effectively as GLP-1 RAs 1, 5
• Risk of euglycemic diabetic ketoacidosis when combined with high-dose insulin therapy, particularly in the setting of acute illness 5

When to Consider SGLT2 Inhibitor Instead:

• If the patient has established heart failure (reduced or preserved ejection fraction), prioritize SGLT2 inhibitor for proven HF hospitalization reduction 1, 2, 5
• If the patient has chronic kidney disease (eGFR 20-60 mL/min/1.73 m²) with albuminuria, prioritize SGLT2 inhibitor for renal protection 1, 5
• If the patient has established atherosclerotic cardiovascular disease, either agent is appropriate, but GLP-1 RAs reduce stroke risk more effectively 1

Practical Implementation Steps

1. Initiate GLP-1 RA at lowest dose (semaglutide 0.25 mg weekly or tirzepatide 2.5 mg weekly) 1, 2
2. Simultaneously reduce basal insulin glargine by 20% (from ~60 U to ~48 U daily) 2, 3
3. Reduce prandial insulin lispro by 10-20% across all meals 2
4. Titrate GLP-1 RA slowly (every 4 weeks) to minimize gastrointestinal side effects 1, 4
5. Continue metformin unless contraindicated 1, 2
6. Monitor for hypoglycemia and further reduce insulin as needed 1, 3

Common Pitfalls to Avoid

• Do not add GLP-1 RA without reducing insulin doses—this substantially increases hypoglycemia risk 1, 2
• Do not combine with DPP-4 inhibitors—no additional glucose lowering and overlapping mechanism 2
• Warn about gastrointestinal side effects (nausea, vomiting, diarrhea)—these are dose-dependent and typically improve with slow titration 1, 4, 6
• Counsel about delayed gastric emptying—this is a class effect that may persist with chronic use 2
• Assess volume status—GLP-1 RAs can cause dehydration in combination with diuretics 1

Future Consideration for Dual Therapy

Once glycemic control is optimized with GLP-1 RA and insulin doses are reduced, consider adding an SGLT2 inhibitor for additive cardiovascular and renal protection if the patient has established ASCVD or multiple risk factors. 1, 2 This sequential approach maximizes glycemic control first, then adds cardio-renal protection without the complexity of initiating both agents simultaneously.