If I max out on Trulicity (dulaglutide), can I switch to another GLP-1 (Glucagon-like peptide-1) receptor agonist at a higher dose?

Switching from Maximum Dose Trulicity to Another GLP-1 Receptor Agonist

Yes, you can switch from maximum dose Trulicity (dulaglutide 1.5 mg weekly) to another GLP-1 receptor agonist at a higher or more potent dose, and this is a well-established clinical practice when glycemic targets are not met or additional weight loss is desired. 1

When to Consider Switching

Switch to a different GLP-1 receptor agonist when you experience any of the following on maximum dose Trulicity (1.5 mg weekly): 1

• HbA1c targets not being met despite adherence to current therapy 1
• Inadequate weight loss when weight reduction is a treatment goal 1
• Desire for cardiovascular risk reduction in patients with established cardiovascular disease (semaglutide and liraglutide have FDA approval for this indication, while dulaglutide does not) 2
• Poor adherence to current regimen 1
• Adverse effects with current GLP-1 receptor agonist 1

Recommended Switch Options

First Choice: Semaglutide (Ozempic/Wegovy)

Semaglutide is the preferred switch option because it provides superior glycemic control and weight loss compared to dulaglutide: 1

• Start at 0.25 mg subcutaneously weekly for 4 weeks, then increase to 0.5 mg weekly 2
• Titrate slowly to 1.0 mg weekly after at least 4 weeks, and if needed, to maximum dose of 2.0 mg weekly (for diabetes) or 2.4 mg weekly (for weight management) 2, 3
• No dose adjustment needed for any level of kidney function, including dialysis patients 2, 4
• FDA-approved for cardiovascular risk reduction in patients with type 2 diabetes and cardiovascular disease 2

Second Choice: Liraglutide (Victoza)

Liraglutide is an alternative if daily injections are acceptable: 2

• Start at 0.6 mg subcutaneously daily 2
• Titrate weekly by 0.6 mg increments to maximum dose of 1.8 mg daily 2
• FDA-approved for cardiovascular risk reduction 2
• No dose adjustment needed for renal or hepatic impairment 2

How to Execute the Switch

Timing and Transition

Stop dulaglutide and start the new GLP-1 receptor agonist at the next scheduled injection time (one week after last dulaglutide dose for weekly agents, or the next day for daily agents). 1

• Do not overlap GLP-1 receptor agonists 1
• Always start at the lowest dose of the new agent, regardless of prior dulaglutide dose, to minimize gastrointestinal side effects 1
• Titrate slowly according to manufacturer recommendations 2, 1

Concomitant Medication Adjustments

If taking insulin or sulfonylureas, reduce their doses by approximately 20% when initiating the new GLP-1 receptor agonist to prevent hypoglycemia: 2, 4, 5

• This applies to basal insulin (glargine, detemir, degludec) 5, 6
• This applies to sulfonylureas (glimepiride, glipizide) 2, 7
• Monitor blood glucose closely during the first 2-4 weeks after switching 5

Managing Gastrointestinal Side Effects

Gastrointestinal symptoms (nausea, vomiting, diarrhea) may recur when switching, even if well-tolerated on dulaglutide: 3, 1

• Counsel patients that these effects are typically transient and improve within 2-4 weeks 3, 1
• Advise reducing portion sizes and limiting high-fat foods 3, 1
• Slow titration is the most effective strategy to minimize these effects 2, 1
• Do not advance doses until gastrointestinal symptoms have resolved 1

Special Considerations by Clinical Context

Patients with Chronic Kidney Disease

All major GLP-1 receptor agonists can be used in CKD, but agent selection varies by eGFR: 2, 4

• Dulaglutide, liraglutide, and semaglutide: No dose adjustment needed at any eGFR, including dialysis 2, 4
• Exenatide once-weekly: Use caution with eGFR 30-59 mL/min/1.73 m²; contraindicated if eGFR <30 2
• Lixisenatide: Contraindicated if eGFR <30 mL/min/1.73 m² 2

Patients with Heart Failure

GLP-1 receptor agonists are safe in heart failure and do not increase hospitalization risk: 2

• Avoid use if recent heart failure decompensation (within 2-4 weeks) 2
• Preferred agents: Liraglutide, semaglutide, or dulaglutide (all have cardiovascular outcomes trial data) 2
• Do not use if taking a DPP-4 inhibitor (saxagliptin, alogliptin) due to heart failure concerns with those agents 2

Patients on Oral Contraceptives

Delayed gastric emptying from GLP-1 receptor agonists may reduce oral contraceptive efficacy: 3

• Add a barrier method for 4 weeks after initiation and after each dose escalation 3
• Consider switching to non-oral contraceptive methods 3

Critical Pitfalls to Avoid

Do not combine two GLP-1 receptor agonists simultaneously - this provides no additional benefit and increases side effects 1

Do not combine with DPP-4 inhibitors (sitagliptin, linagliptin, saxagliptin, alogliptin) - these work on the same pathway and combination is not recommended 2, 4

Do not forget to reduce insulin/sulfonylurea doses - failure to do so significantly increases hypoglycemia risk 2, 4, 5

Do not use exenatide or lixisenatide in severe renal impairment (eGFR <30 mL/min/1.73 m²) - these are absolute contraindications 2, 4

Do not ignore personal or family history of medullary thyroid carcinoma or MEN 2 syndrome - all GLP-1 receptor agonists are contraindicated in these patients 2, 3

Do not prescribe in pregnancy - all GLP-1 receptor agonists should be discontinued if pregnancy occurs 2, 3