Switching from Ozempic 2.5mg to Zepbound 5mg in a 74-Year-Old Woman
Yes, it is appropriate to switch this 74-year-old woman from Ozempic (semaglutide) 2.5mg to Zepbound (tirzepatide) 5mg, as tirzepatide demonstrates superior glycemic control and weight reduction compared to semaglutide, with an acceptable safety profile in older adults. 1, 2
Rationale for the Switch
Superior Efficacy of Tirzepatide
Tirzepatide 5mg provides comparable or superior HbA1c reduction to semaglutide 1mg (the maximum approved dose for diabetes), with mean HbA1c reductions of approximately -1.60% versus -1.39% respectively. 2
Direct head-to-head comparison (SURPASS-2 trial) demonstrated tirzepatide's superiority: At 40 weeks, tirzepatide 5mg reduced HbA1c by -2.01 percentage points compared to semaglutide 1mg at -1.86 percentage points, with a statistically significant difference of -0.15 percentage points (P=0.02). 1
Weight loss is substantially greater with tirzepatide: Tirzepatide 5mg produced 1.9 kg more weight loss than semaglutide 1mg in direct comparison (P<0.001). 1
Appropriate Dosing Strategy
The FDA-approved starting dose for tirzepatide is 2.5mg weekly for 4 weeks, then escalate to 5mg weekly. The 2.5mg dose is for treatment initiation only and is not intended for glycemic control. 3
Since your patient is currently on semaglutide 2.5mg (which appears to be a non-standard dose, as approved doses are 0.25mg, 0.5mg, 1mg, or 2mg weekly), starting tirzepatide at 2.5mg for 4 weeks before advancing to 5mg minimizes gastrointestinal side effects. 3
Special Considerations for Older Adults
Glycemic Target Appropriateness
With an HbA1c of 7%, this patient is already at a reasonable glycemic target for a 74-year-old. For relatively healthy older adults with good functional status, an HbA1c goal of 7% or lower is appropriate, while for frail older adults, a less stringent target of 8% is acceptable. 4
The switch may be justified if additional benefits beyond glycemic control are desired, such as weight reduction, cardiovascular protection, or kidney protection, rather than purely for tighter glucose control. 4
Safety Profile in Older Adults
GLP-1 receptor agonists (including tirzepatide as a dual GIP/GLP-1 agonist) carry low hypoglycemia risk, which is particularly important in older adults. 4
No dose adjustment is required for tirzepatide based on age alone. 3
Gastrointestinal side effects (nausea 17-22%, diarrhea 13-16%, vomiting 6-10%) are the most common adverse events but are typically mild to moderate and transient. 1
Critical Safety Screening Before Initiation
Absolute Contraindications
Screen for personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), as tirzepatide is absolutely contraindicated in these patients. 3
Verify no known serious hypersensitivity to tirzepatide or its excipients. 3
Relative Precautions
Use caution if history of pancreatitis exists, though tirzepatide has not been specifically studied in patients with prior pancreatitis. 3
Assess kidney function: While no dose adjustment is required for tirzepatide based on eGFR (unlike some other diabetes medications), GLP-1 receptor agonists like semaglutide and dulaglutide require no dose adjustment for kidney function, and tirzepatide follows similar principles. 4
Perioperative Considerations
If any elective surgery is planned, inform the surgical team early that the patient will be on tirzepatide. Consider discontinuing tirzepatide 10-14 days before elective surgery due to delayed gastric emptying and aspiration risk. 4, 5
The elimination half-life of tirzepatide is approximately 5 days, compared to 7 days for semaglutide, which informs perioperative timing decisions. 4
Monitoring Plan
Assess HbA1c at 3-4 months after reaching the maintenance dose to evaluate glycemic response. 4
Monitor for gastrointestinal symptoms during dose escalation, particularly during the first 4-8 weeks. 3, 1
Watch for signs of pancreatitis, gallbladder symptoms, and blood pressure changes. 5
If the patient is on sulfonylureas or insulin, consider dose reduction to minimize hypoglycemia risk, though this patient appears to be on semaglutide monotherapy. 4
Common Pitfalls to Avoid
Do not skip the 2.5mg initiation dose: Starting directly at 5mg increases gastrointestinal side effects. 3
Do not use tirzepatide and a DPP-4 inhibitor together, as there is no added glucose-lowering benefit. 4
Do not assume the patient needs tighter glycemic control: At age 74 with HbA1c of 7%, the primary benefits may be weight reduction and cardiometabolic protection rather than further HbA1c lowering. 4