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How do GLPs compare beyond the weight-loss headline?

Compare matched trials, body composition and treatment experience.

Direct comparisons exist for some regimens. A larger percentage in a separate study cannot by itself establish superiority.

SURMOUNT-5, NEJM SURMOUNT-5, NEJM Retatrutide phase 2 obesity trial
Compare measured outcomesWatch relevant trials
Human

How does tirzepatide compare with semaglutide for weight loss?

20.2% weight reduction

72 weeks; maximum tolerated tirzepatide 10/15 mg versus semaglutide 1.7/2.4 mg; adults without diabetes.

Demonstrated findings

Average body-weight reduction was 20.2% with tirzepatide and 13.7% with semaglutide at 72 weeks.

What might this mean? · interpretation

This direct comparison favors tirzepatide for the tested weight-loss outcome and regimens.

What might this mean, and what would change the interpretation?

Adults with obesity without diabetes; open-label trial. It does not compare all doses or establish an overall winner for every health outcome.

What would clarify this: Longer follow-up and comparisons covering body composition, tolerability and clinical outcomes.

SURMOUNT-5, NEJM
Human · SemaglutideWhat did semaglutide achieve in the direct comparison?
Human

What did semaglutide achieve in the direct comparison?

13.7% weight reduction

72 weeks; maximum tolerated semaglutide 1.7/2.4 mg versus tirzepatide 10/15 mg; adults without diabetes.

Demonstrated findings

Participants assigned semaglutide lost an average of 13.7% of body weight at 72 weeks, versus 20.2% with tirzepatide.

What might this mean? · interpretation

Semaglutide produced substantial weight reduction in this trial, with a smaller average reduction than the comparator.

What might this mean, and what would change the interpretation?

This result applies to the studied regimens and population. Weight change does not establish preservation of muscle or long-term cardiovascular benefit.

What would clarify this: Endpoint-specific comparisons using matched populations and durations.

SURMOUNT-5, NEJM
Human · RetatrutideHow strong is the weight-loss signal for retatrutide?
Human

How strong is the weight-loss signal for retatrutide?

24.2% weight reduction

48 weeks; highest-dose group, 12 mg; randomized phase 2 trial, 338 adults.

Demonstrated findings

The highest-dose group lost an average of 24.2% of body weight at 48 weeks, versus 2.1% with placebo.

What might this mean? · interpretation

The phase 2 result supports a substantial weight-loss signal worthy of further comparison.

What might this mean, and what would change the interpretation?

This is a separate trial from SURMOUNT-5. Its percentages cannot establish superiority to tirzepatide or semaglutide. Gastrointestinal events and heart-rate increases were reported.

What would clarify this: Direct comparator trials and longer-term outcomes, including body composition.

Retatrutide phase 2 obesity trial
Human · TirzepatideHow much of the weight lost was lean mass?
Human

How much of the weight lost was lean mass?

10.9% lean-mass reduction

SURMOUNT-1 DXA substudy: 124 tirzepatide and 36 placebo participants; 72 weeks.

Demonstrated findings

At 72 weeks, fat mass fell 33.9% and lean mass 10.9% with pooled tirzepatide doses, versus 8.2% and 2.6% with placebo. About a quarter of the weight lost was lean mass in both groups.

Limitations & adverse findings

Both fat and lean mass declined. These results do not establish muscle preservation.

What might this mean? · interpretation

The proportion of weight loss attributed to lean mass differs from the percentage of starting lean mass lost.

What might this mean, and what would change the interpretation?

DXA lean mass is not a direct measure of contractile muscle or strength. This was a 160-person substudy, not the full randomized population.

What would clarify this: Muscle function, regional muscle measures and longer-term follow-up.

Findings reviewed · abstract

Checked Sep 15, 2026 against the linked abstract. This reading note is not a formal risk-of-bias appraisal.

The source links a published correction (DOI 10.1111/dom.70050). Correction text was unavailable in this review; values here are from the current abstract.

SURMOUNT-1 body-composition substudy
Human · SemaglutideWhat did the direct comparison with liraglutide show?
Human

What did the direct comparison with liraglutide show?

15.8% weight reduction

338 adults; semaglutide 2.4 mg weekly versus liraglutide 3 mg daily.

Demonstrated findings

Mean weight reduction was 15.8% with semaglutide and 6.4% with liraglutide at 68 weeks.

Limitations & adverse findings

Gastrointestinal events were common in both groups.

What might this mean? · interpretation

This directly compares the two studied regimens for weight loss.

What might this mean, and what would change the interpretation?

Open-label comparison in adults without diabetes; other doses and outcomes need separate evidence.

What would clarify this: Longer follow-up and matched body-composition outcomes.

Findings reviewed · abstract

Checked Sep 15, 2026 against the linked abstract. This reading note is not a formal risk-of-bias appraisal.

STEP 8 randomized trial, JAMA
Human · LiraglutideHow did liraglutide perform in STEP 8?
Human

How did liraglutide perform in STEP 8?

6.4% weight reduction

Daily liraglutide 3 mg versus weekly semaglutide 2.4 mg.

Demonstrated findings

Mean weight reduction was 6.4%, versus 15.8% with semaglutide at 68 weeks.

Limitations & adverse findings

Treatment discontinuation for any reason: 27.6% versus 13.5% with semaglutide.

What might this mean? · interpretation

Liraglutide produced weight loss, with a smaller average change in this direct comparison.

What might this mean, and what would change the interpretation?

These results apply to the tested regimens in adults without diabetes.

What would clarify this: Comparisons of outcomes beyond body weight.

Findings reviewed · abstract

Checked Sep 15, 2026 against the linked abstract. This reading note is not a formal risk-of-bias appraisal.

STEP 8 randomized trial, JAMA

What would move this question forward?

How do compounds compare when duration, population, dose strategy and outcome definitions align?

  • Weight change and analysis population
  • Fat and lean mass
  • Adverse events and treatment discontinuation
  • Direct comparator versus separate trial

For emerging mechanisms, replication and the absence of the predicted effect both matter. Human implications remain hypotheses until the relevant outcomes are tested.

Community experiences & questions

A sourced community summary has not been prepared for this question yet. The compound pages link to public discussions for further exploration.

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Keep exploring

What has been studied for preserving muscle during weight loss?Does more lean mass mean more strength?