Choosing a first weight-loss injection

Semaglutide and tirzepatide are approved options that can help with appetite and weight. Retatrutide is still investigational. The best fit also depends on side effects, your health and whether you can keep accessing treatment.

Tirzepatide led to more average weight loss in a direct trial. That result is useful, but it cannot pick the best medicine for every person—or rank retatrutide alongside it.

Compare starting doses Compare trial results

The difference to know first

US weight-management context

  • Semaglutide

    Wegovy injection
    Approved option
    GLP-1

  • Tirzepatide

    Zepbound
    Approved option
    GLP-1GIP

  • Retatrutide

    Investigational medicine
    Still in research
    GLP-1GIPGlucagon
More hormone targets do not automatically mean a better fit. Retatrutide has phase 3 results, but no approved product or prescribing dose.

Starting dose is not the maintenance dose

0.25 mg weekly

Wegovy / semaglutide

First four weeks. Gradual escalation to adult weight-management maintenance of 1.7 or 2.4 mg weekly.

2.5 mg weekly

Zepbound / tirzepatide

First four weeks, then 5 mg. Weight-management maintenance options are 5, 10 or 15 mg weekly.

Research only

Retatrutide

No approved starting-dose instructions. Trial schedules are specific to the research.

The first month is a starting stage, not the full test of treatment. Both labels gradually increase doses according to response and tolerability. Treatment is ongoing, with no fixed cycle. Wegovy also permits 7.2 mg for selected adults needing further weight reduction after at least four weeks tolerating 2.4 mg; that dose was outside the comparison below. Wegovy label, Zepbound label.

For study-specific retatrutide amounts, see the retatrutide profile.

What the names mean

The ingredient and brand are different names. Wegovy and Ozempic contain semaglutide; Zepbound and Mounjaro contain tirzepatide. Their approved uses, devices and doses differ. This guide compares adult weight-management weekly injections; oral semaglutide has separate instructions. Ozempic label, Mounjaro label.

The hormone targets in the visual help explain terms such as “dual” and “triple agonist.” Retatrutide targets GLP-1, GIP and glucagon—not a hormone called “GLP-3.” More targets do not automatically establish greater benefit or fewer side effects. Wegovy, Zepbound, Lilly’s retatrutide update.

Efficacy: what the data says

Tirzepatide produced more average weight loss at the doses tested in SURMOUNT-5. The 72-week trial enrolled 751 adults with obesity without diabetes. Participants and investigators knew which medicine was assigned.

SURMOUNT-5: average weight reduction at 72 weeks

Tirzepatide 10 or 15 mg
20.2 %
Semaglutide 1.7 or 2.4 mg
13.7 %
Weekly injections at maximum tolerated study doses. These group averages describe this trial; they do not predict an individual’s result or compare every dose/formulation available today. SURMOUNT-5 primary publication

Where does retatrutide fit? It now has published phase 3 results, including the 80-week TRIUMPH-1 trial against placebo. That is a separate trial with different doses, duration and methods—not a third arm of SURMOUNT-5. It does not establish a three-way winner. Retatrutide remains unapproved. TRIUMPH-1 publication, current development status.

Pharmacokinetics compared

The same milligrams are not equivalent across medicines. Injected semaglutide has an approximate one-week half-life; tirzepatide’s is about five to six days. Some medicine remains when the next weekly dose arrives, so levels build over several weeks. That timing does not provide a switching-dose conversion or predict weight loss. Wegovy pharmacology, Zepbound pharmacology.

Side-effect profiles

Neither choice guarantees an easier stomach. Digestive effects were the most common adverse events in SURMOUNT-5, mostly during dose increases. Individual experiences vary. Persistent severe abdominal pain, repeated vomiting or inability to keep fluids down need assessment. See the direct side-effect comparison.

Medical history matters, including pregnancy plans, other medicines and digestive conditions. Both labels include thyroid C-cell tumor warnings and exclude people with a personal/family history of medullary thyroid carcinoma or MEN2. Tirzepatide can reduce oral hormonal contraceptive effectiveness; its label calls for a non-oral method or added barrier protection for four weeks after starting and after each dose increase. Wegovy precautions, Zepbound precautions.

A useful first-prescription conversation

Plan beyond the first injection

  1. Define the goal

    Discuss weight-related health, diabetes and other conditions that may affect the product choice.

  2. Plan tolerability and nutrition

    Agree what to do if symptoms limit food, fluid intake or activity, and how to protect strength.

  3. Plan follow-up and access

    Review response, affordability, supply and what happens if treatment needs to change or stop.

Weight regain after stopping is not simply evidence of inadequate willpower. In SURMOUNT-4, withdrawing tirzepatide led to substantial regain despite the study’s lifestyle intervention, while continued treatment maintained and increased weight loss. Long-term management deserves discussion before starting. Randomized withdrawal trial.

Reading the curves

Compare the three example curves to see timing and overlap. Different medicines are normalized for comparison: the tallest curve does not identify the most effective treatment. See muscle and lean-mass preservation for the separate body-composition question.

Frequently asked questions

Which GLP-1 should I start with?

Discuss the treatment indication, medical history, tolerability and ongoing access with the prescriber. Semaglutide and tirzepatide have approved products; retatrutide remains investigational.

Can I switch using the same milligram dose?

No universal equal-milligram conversion exists. A change needs product-specific starting-dose and timing instructions that account for the previous treatment and side effects.

Will weight return if treatment stops?

Withdrawal studies show substantial regain can occur even with lifestyle support. Plan follow-up and long-term management rather than assuming a short course provides a permanent effect.

Sources and study context

Checked October 11, 2026. US injection labels provide the dose context.

  • Wegovy prescribing information, sections 1–2, 4–8 and 12: weight-management injection dosing, contraindications and pharmacology. Its 7.2 mg option was outside SURMOUNT-5.
  • Zepbound prescribing information, sections 1–2, 4–8 and 12: starting/maintenance doses, contraception precaution and five-to-six-day half-life.
  • Ozempic and Mounjaro: ingredient and diabetes-brand context.
  • SURMOUNT-5: direct randomized, open-label comparison; maximum tolerated study doses; 72-week group averages.
  • TRIUMPH-1: 80-week, placebo-controlled phase 3 retatrutide trial. Lilly’s status update identifies it as investigational and unapproved.
  • SURMOUNT-4: randomized withdrawal of tirzepatide after an initial treatment period; supports planning for ongoing management.