----------|-------------|-------------| | Nausea | 44% | 31% | | Diarrhea | 30% | 23% | | Vomiting | 25% | 12% | | Constipation | 24% | 17% | | Discontinuation due to AEs | 7% | 4-7% |
Tirzepatide appears to have a milder GI side effect profile than semaglutide, with notably lower rates of vomiting. The GIP component may provide a "buffering" effect that reduces nausea.
This matters for adherence. Men who get severely nauseated in the first weeks often quit before reaching therapeutic doses. Tirzepatide's gentler introduction may help more men stick with treatment.
Winner: Tirzepatide, slightly milder GI profile.
Dosing and Titration
Semaglutide (Wegovy): - Starting dose: 0.25mg weekly - Titration: Increase every 4 weeks - Schedule: 0.25 → 0.5 → 1.0 → 1.7 → 2.4mg - Time to maintenance: 16-20 weeks
Tirzepatide (Zepbound): - Starting dose: 2.5mg weekly - Titration: Increase every 4 weeks - Schedule: 2.5 → 5 → 7.5 → 10 → 12.5 → 15mg - Time to maintenance: 20+ weeks
Both require slow titration. Rushing leads to severe side effects and dropouts. The schedules are similar in duration, though tirzepatide has more dose options, allowing finer adjustment if you hit a dose that causes problems.
Tie — both require patience.
Forms Available
Semaglutide: - Wegovy: Weekly injection for weight loss - Wegovy Pill: Daily oral (approved December 2025) - Ozempic: Weekly injection for diabetes (often used off-label) - Rybelsus: Daily oral for diabetes
Tirzepatide: - Zepbound: Weekly injection for weight loss - Mounjaro: Weekly injection for diabetes
Semaglutide's big advantage: an oral option now exists. The Wegovy pill launched January 2026. For men who won't inject themselves under any circumstances, this changes the calculation entirely.
Eli Lilly is developing an oral tirzepatide, but it's not expected for several years.
Winner: Semaglutide, for having an oral option.
Cost Comparison
Without insurance (retail pricing, January 2026):
| Medication | Monthly Cost |
|---|---|
| Wegovy (injection) | $1,300-1,400 |
| Wegovy Pill | $149-299* |
| Zepbound | $1,000-1,100 |
*Wegovy Pill pricing through Novo Nordisk programs; promotional through 2026.
Zepbound is slightly cheaper at retail than Wegovy injection. But the Wegovy Pill's promotional pricing dramatically undercuts both injectable options — if you qualify for the manufacturer programs.
Insurance coverage varies by plan. Both are often covered similarly when they're covered at all. The diabetes versions (Ozempic, Mounjaro) sometimes have better coverage than the weight-loss versions (Wegovy, Zepbound) depending on your insurer.
With manufacturer programs: - LillyDirect offers Zepbound at ~$550/month for self-pay - NovoCare offers Wegovy savings cards reducing copays to $25/month with commercial insurance
Winner: Context-dependent. Wegovy Pill is cheapest if you qualify. LillyDirect makes Zepbound affordable for self-pay. Insurance coverage is plan-specific.
The Decision Framework
Choose semaglutide (Wegovy/Ozempic) if:
- You have existing cardiovascular disease or significant risk factors — the SELECT trial data provides proven protection
- You refuse injections — Wegovy Pill is your only FDA-approved oral option for weight loss
- You're on a budget — Wegovy Pill promotional pricing is the cheapest option currently
- You want the most-studied option — semaglutide has years more real-world data
- Your insurance covers Wegovy but not Zepbound
Choose tirzepatide (Zepbound/Mounjaro) if:
- Maximum weight loss is the priority — 5-6 percentage points more than semaglutide
- You have obstructive sleep apnea — only GLP-1 FDA-approved for this indication
- You've tried semaglutide and plateaued — switching to tirzepatide often restarts progress
- You had severe GI side effects on semaglutide — tirzepatide may be gentler
- Your insurance covers Zepbound but not Wegovy
What About Combining or Switching?
Switching from semaglutide to tirzepatide: Common approach when weight loss stalls. Most providers recommend stopping semaglutide, starting tirzepatide at the lowest dose (2.5mg), and titrating up as usual. Don't try to shortcut the titration because you were already on a GLP-1 — the mechanisms aren't identical, and your body needs to adjust.
Switching from tirzepatide to semaglutide: Less common, but sometimes done for cost reasons (especially with Wegovy Pill launch) or to access the cardiovascular protection data. Same approach — start low, titrate normally.
Combining both: Not recommended. They target overlapping pathways, so doubling up likely just doubles side effects without proportional benefit. No clinical data supports combination use.
The Pipeline Changes This Calculation
By 2027, this comparison may be obsolete.
Retatrutide — Eli Lilly's triple agonist (GLP-1/GIP/glucagon) — showed 28.7% weight loss in Phase 3 trials. That's roughly 8 percentage points better than tirzepatide, which was already better than semaglutide.
Orforglipron — Eli Lilly's oral GLP-1 with no food restrictions — could hit the market in 2026. Unlike Wegovy Pill (which requires 30-minute fasting), orforglipron can be taken anytime.
Amycretin — Novo Nordisk's next-gen candidate — showed 24.3% weight loss at 36 weeks with no plateau in sight. Could be the "best-in-class" Novo option.
If you're making a long-term decision today, the medication you start may not be the medication you end up on. Choose based on current needs and stay aware of emerging options.
Bottom Line for Men
For most men prioritizing weight loss: Tirzepatide (Zepbound) produces better results.
For men with heart disease or high cardiovascular risk: Semaglutide (Wegovy) has proven outcomes data that tirzepatide doesn't — yet.
For men who won't inject: Wegovy Pill is currently the only option.
For men with sleep apnea: Tirzepatide (Zepbound) is specifically FDA-approved.
Both medications will help you lose significant weight, improve testosterone levels, and reduce metabolic disease risk. You're not making a wrong choice between them — you're optimizing for your specific situation.
The best medication is the one you can access, afford, tolerate, and actually take consistently.
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Related Articles: - GLP-1 Medications for Men: The Complete 2026 Guide - Best Telehealth Providers for Men's GLP-1 Prescriptions - Oral vs Injectable GLP-1s: What Men Need to Know
Last updated: January 2026
Medical disclaimer: This content is for informational purposes only and does not constitute medical advice. Consult a healthcare provider before starting any medication.