What alternative medication can be used for a patient who cannot take Jardiance (empagliflozin) and does not have access to Trulicity (dulaglutide) or Zepbound (tirzepatide)?

Alternative GLP-1 Receptor Agonist Options for Type 2 Diabetes

For patients unable to take Jardiance (empagliflozin) and without access to dulaglutide, semaglutide, or tirzepatide, liraglutide (Victoza) is the preferred alternative GLP-1 receptor agonist, as it has demonstrated cardiovascular benefit in major outcome trials and can be used across a wide range of kidney function. 1

Primary Recommendation: Liraglutide

Liraglutide should be initiated at 0.6 mg once daily subcutaneously and titrated weekly by 0.6 mg increments to the target dose of 1.2-1.8 mg daily. 1 This agent provides:

• Proven cardiovascular benefit with reduction in major adverse cardiovascular events (MACE) including cardiovascular deaths, nonfatal MI, and nonfatal strokes independent of glucose control 1
• Kidney protection with reduced albuminuria and slowed eGFR decline, with particularly strong MACE risk reduction in patients with eGFR <60 mL/min/1.73 m² 1
• No dose adjustment required for patients with chronic kidney disease, including those with eGFR as low as 15 mL/min/1.73 m² 1
• Low hypoglycemia risk when used without sulfonylureas or insulin 1

Practical Initiation Strategy

Start with 0.6 mg daily for at least one week before increasing the dose. 2 If nausea occurs:

• Consider increasing by 0.3 mg weekly instead of 0.6 mg weekly 2
• Extend the titration interval to every 2 weeks or monthly rather than weekly 2
• Many patients achieve adequate glycemic control at 1.2 mg without needing the full 1.8 mg dose 2

The most common side effects are gastrointestinal (nausea in 10-29%, vomiting, diarrhea), which typically improve with dose titration and resolve over several weeks to months. 1

Secondary Alternative: Exenatide Once-Weekly

If liraglutide is unavailable or not tolerated, exenatide once-weekly (Bydureon) at 2 mg subcutaneously weekly is an alternative option that has demonstrated cardiovascular safety. 1 However:

• Do not use if eGFR <30 mL/min/1.73 m² 1
• It has not demonstrated the same cardiovascular benefit as liraglutide 1
• Requires dose adjustment in moderate renal impairment 1

Third-Line Option: Lixisenatide

Lixisenatide (Lyxumia) 10-20 mcg once daily is another alternative, though it:

• Has demonstrated cardiovascular safety but not cardiovascular benefit 1
• Should not be used if eGFR <30 mL/min/1.73 m² 1
• Is less potent for glycemic control compared to liraglutide 1

Critical Contraindications and Cautions

Avoid all GLP-1 receptor agonists in patients with: 1

• Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia type 2 (MEN2) 1
• Active gallbladder disease 1
• History of gastroparesis 1
• Recent heart failure decompensation (within past few weeks) 1

Monitoring Requirements

After initiating liraglutide: 1

• Monitor glucose closely for the first 4 weeks, especially if on insulin, sulfonylureas, or glinides 1
• Consider reducing sulfonylurea dose or discontinuing it entirely to minimize hypoglycemia risk 1
• For patients on insulin, reduce total daily insulin dose by approximately 20% at initiation 1
• Educate patients about symptoms of dehydration (lightheadedness, orthostasis, weakness) 1

Why Not Other Alternatives?

Metformin alone may be insufficient if the patient previously required Jardiance, suggesting more advanced disease requiring agents with cardiovascular and kidney benefits. 1

DPP-4 inhibitors (sitagliptin, linagliptin) are significantly less potent for glycemic control and lack the cardiovascular and kidney benefits of GLP-1 receptor agonists. 1

Pioglitazone is contraindicated if the patient has heart failure and carries risks of weight gain, edema, and fractures. 1

Sulfonylureas should only be considered as a last resort due to high hypoglycemia risk and lack of cardiovascular benefit. 1