What alternative medication can be used for a type 2 diabetes patient who cannot tolerate Jardiance (empagliflozin)?

Alternative Medication for Type 2 Diabetes When Jardiance (Empagliflozin) is Not Tolerated

If a patient cannot tolerate Jardiance (empagliflozin), a GLP-1 receptor agonist with proven cardiovascular benefit—specifically liraglutide, semaglutide, or dulaglutide—should be the preferred alternative, particularly if the patient has chronic kidney disease, established cardiovascular disease, or high cardiovascular risk. 1, 2

Primary Alternative: GLP-1 Receptor Agonists

GLP-1 receptor agonists are the guideline-recommended alternative when SGLT2 inhibitors cannot be used. The ADA/KDIGO consensus explicitly states that a GLP-1 receptor agonist with proven cardiovascular benefit is recommended for patients with type 2 diabetes and CKD who do not meet their individualized glycemic target with metformin and/or an SGLT2i or who are unable to use these drugs 1. This recommendation extends to patients with established atherosclerotic cardiovascular disease or high cardiovascular risk 1, 2.

Specific GLP-1 Receptor Agonist Options:

• Liraglutide (Victoza): Demonstrated cardiovascular mortality reduction, with particularly strong benefits in patients with eGFR <60 mL/min/1.73 m² 1, 3
• Semaglutide (Ozempic): Proven cardiovascular benefits with once-weekly dosing 1, 4
• Dulaglutide: Demonstrated cardiovascular benefits and showed slower GFR decline compared to insulin glargine in patients with moderate-to-severe CKD 1

Expected Outcomes with GLP-1 Receptor Agonists:

• HbA1c reduction of 0.7-1.0% 2, 5
• Significant weight loss (unlike sulfonylureas or insulin) 2, 5
• Low hypoglycemia risk when used without insulin or sulfonylureas 5
• Cardiovascular mortality reduction in high-risk patients 1
• Renal protective effects including reduced albuminuria and slower eGFR decline 1

Common Side Effects to Anticipate:

Nausea, vomiting, and diarrhea occur in 15-20% of patients but usually abate over several weeks to months with dose titration 1. Start with the lowest dose and titrate gradually to minimize gastrointestinal symptoms 4, 3.

Alternative SGLT2 Inhibitors

If the intolerance to Jardiance is due to a specific side effect rather than a class effect, consider switching to another SGLT2 inhibitor:

• Dapagliflozin: Approved for use down to eGFR 25 mL/min/1.73 m² 1
• Canagliflozin: Demonstrated renal benefits in the CREDENCE trial with 30% reduction in development of ESRD 1

However, all SGLT2 inhibitors share similar adverse effect profiles including genital infections, volume depletion, and diabetic ketoacidosis risk 6, 7.

Other Alternatives Based on Clinical Context

If Cardiovascular Disease or CKD is NOT Present:

DPP-4 inhibitors are reasonable alternatives with:

• Intermediate glucose-lowering effect (0.7-1.0% HbA1c reduction) 2
• Weight neutral 5
• Low hypoglycemia risk 5
• No dose adjustment needed until eGFR <45 mL/min/1.73 m² 2
• Suitable for elderly patients or those with hypoglycemia concerns 5

Important caveat: Never combine GLP-1 receptor agonists with DPP-4 inhibitors as they work through similar mechanisms without additive benefit 2.

If Cost is a Major Barrier:

Sulfonylureas (glimepiride or glipizide) provide:

• High glucose-lowering effect (0.9-1.1% HbA1c reduction) 5
• Very low cost 1
• Major drawbacks: Moderate to high hypoglycemia risk and weight gain 5
• Initiate conservatively and titrate slowly to avoid hypoglycemia 1
• Avoid glyburide due to higher hypoglycemia risk 1

Critical Decision Points

Continue Metformin:

Always continue metformin when adding a second agent unless contraindicated (eGFR <30 mL/min/1.73 m²) or not tolerated 1, 2.

Reassess in 3 Months:

Evaluate HbA1c after approximately 3 months of the new therapy and proceed to triple therapy or insulin if the A1C target is not achieved 2.

Special Circumstances Requiring Immediate Insulin:

If the patient has A1C ≥10% (86 mmol/mol) and/or blood glucose ≥300 mg/dL with symptoms, or ketosis/ketoacidosis, initiate insulin therapy immediately rather than trying oral alternatives 2.

Common Pitfalls to Avoid

• Do not delay treatment intensification while waiting to see if the patient can tolerate another SGLT2 inhibitor if cardiovascular or renal disease is present—move directly to a GLP-1 receptor agonist 2, 5
• Do not use thiazolidinediones (pioglitazone) in patients with heart failure due to fluid retention risk 1
• Do not prescribe sympathomimetic agents (phentermine) in patients with cardiovascular disease 1
• Monitor renal function when initiating GLP-1 receptor agonists, especially if the patient experiences severe gastrointestinal symptoms that could lead to dehydration and acute kidney injury 4