Replacement Options for Ozempic (Semaglutide)
For patients requiring alternatives to Ozempic (semaglutide), other GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists offer the most comparable efficacy for glycemic control and weight management.
Alternative GLP-1 Receptor Agonists
Dulaglutide (once weekly): Provides high glucose-lowering efficacy with cardiovascular benefits and renal endpoint improvements, though slightly less potent than semaglutide for weight loss 1
Liraglutide (once daily): Offers high glucose-lowering efficacy with proven cardiovascular benefits and renal endpoint improvements; FDA-approved for both diabetes (Victoza) and obesity (Saxenda at 3.0 mg dose) 1
Exenatide (twice daily or once weekly): The twice-daily formulation provides intermediate glucose-lowering with stronger postprandial effects, while the once-weekly formulation offers improved adherence 1, 2
Lixisenatide (once daily): Provides intermediate glucose-lowering with stronger postprandial effects similar to exenatide twice daily 1, 2
Dual GIP and GLP-1 Receptor Agonist
- Tirzepatide (once weekly): Very high glucose-lowering efficacy with superior weight loss compared to semaglutide (5.1% greater weight loss) and liraglutide (13.0% greater weight loss); FDA-approved for both diabetes (Mounjaro) and obesity (Zepbound) 1
Oral Options
- Oral semaglutide: Available in various doses (7 mg, 14 mg for diabetes; 25 mg and 50 mg being studied for obesity); the 25 mg dose demonstrated 13.6% weight reduction in clinical trials 1, 3
Considerations When Switching Between GLP-1 RAs
Medical triggers for switching include: unmet HbA1c targets, desire for additional weight loss, poor adherence, increased cardiovascular risk status, or adverse effects with current GLP-1 RA 4
When switching between GLP-1 RAs, consider:
- Previous GLP-1 RA dose and treatment duration
- Patient's experience with prior GLP-1 RA initiation
- Concomitant treatments and clinical characteristics 4
Managing gastrointestinal side effects when switching:
- Slow dose titration
- Reduced food portion sizes
- Decreased fat intake 4
Efficacy Comparison
Weight loss efficacy (highest to lowest):
- Tirzepatide (15-20.9% weight loss)
- Semaglutide (14.9-16% weight loss)
- Liraglutide (8% weight loss)
- Other GLP-1 RAs (lower percentages) 1
Glycemic control efficacy (highest to lowest):
Non-GLP-1 RA Alternatives
SGLT2 inhibitors (canagliflozin, empagliflozin, dapagliflozin): Provide intermediate glucose-lowering efficacy with cardiovascular and renal benefits, plus moderate weight loss 1
DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, alogliptin): Offer intermediate glucose-lowering with neutral weight effects and minimal hypoglycemia risk 1
Metformin: Provides high glucose-lowering efficacy with neutral to modest weight loss effects; remains first-line therapy for type 2 diabetes 1
Important Clinical Considerations
Gastric emptying effects: Short-acting GLP-1 RAs (exenatide twice daily, lixisenatide) maintain their effect on gastric emptying during long-term treatment, while long-acting agents (semaglutide, liraglutide, dulaglutide) show tachyphylaxis over time 1
Perioperative risk: GLP-1 RAs are associated with delayed gastric emptying and increased risk of retained gastric contents despite appropriate fasting, which may increase aspiration risk during procedures 1
Cardiovascular benefits: Dulaglutide, liraglutide, and semaglutide have demonstrated cardiovascular benefits, making them preferred options for patients with established atherosclerotic cardiovascular disease 1, 2
Renal benefits: Several GLP-1 RAs have shown benefits for renal endpoints in cardiovascular outcome trials, particularly for albuminuria outcomes 1
Remember that when switching between GLP-1 RAs, an individualized approach based on patient characteristics, comorbidities, and preferences will optimize outcomes and minimize adverse effects.