Beyond Weight Loss: Muscle Preservation and the Next Phase of GLP-1 Research

Evidence reviewed: 14 September 2026. The drug combinations discussed below are investigational for muscle preservation during obesity treatment. This article describes research, not a treatment protocol.

Abstract

A lower number on the scale is useful information, but it does not show which tissues changed or whether everyday movement became easier. As obesity treatments produce substantial weight reduction, researchers are asking a more detailed question: how much of that change is fat, how much is lean tissue, and what happens to physical function?

New studies of bimagrumab with semaglutide and apitegromab with tirzepatide have brought muscle preservation into the discussion. Their findings deserve attention without turning every decrease in measured lean mass into a diagnosis of muscle damage.

This review explains the measurements, examines the clinical evidence and considers what remains uncertain. The aim is to understand treatment quality through several outcomes, rather than replace one headline percentage with another.

Lean Mass Is Not the Same as Skeletal Muscle

Dual-energy X-ray absorptiometry, usually shortened to DXA, separates body composition into fat, bone mineral and lean soft tissue. The lean compartment includes muscle, organs and water. It is therefore broader than skeletal muscle alone. [1]

If a scan reports a two-kilogram reduction in lean mass, it cannot automatically be translated into two kilograms of lost contractile muscle. Equally, a favourable scan does not directly measure the ability to climb stairs or carry groceries. Each measurement answers a particular question.

Terminology also matters when reading a trial. “Lean mass,” “fat-free mass,” “appendicular lean mass” and “muscle volume” are related measures, but they are not interchangeable. Look for the actual method and body compartment before interpreting the result.

A Percentage Can Improve While an Absolute Amount Falls

Consider a simplified example: a person starts with 60 kg of lean tissue within a 100 kg total body weight. Later, they have 57 kg of lean tissue within 90 kg total weight. Their lean proportion rose from 60% to about 63%, even though the absolute amount declined.

This is an arithmetic illustration, not a predicted treatment response. It shows why a report of “improved lean proportion” and a report of “reduced lean mass” can both be correct.

Muscle Strength and Function Need Their Own Assessment

The revised European consensus on sarcopenia places low strength at the centre of assessment, uses muscle quantity or quality to confirm the diagnosis and considers physical performance when judging severity. A single body-composition change is not sufficient to diagnose sarcopenia. [2]

This distinction prevents two errors: dismissing persistent weakness because weight loss looks successful, and assuming someone has developed a muscle disease solely because a scan reports less lean tissue.

A useful clinical discussion includes both measurements and lived function. Changes in walking, rising from a chair or handling usual tasks deserve context. Pain, illness and other factors can also influence these activities, so a change is a reason for assessment rather than a self-diagnosis.

What SURMOUNT-1 Shows About Tirzepatide

The SURMOUNT-1 DXA analysis included 160 participants with baseline and follow-up scans. At week 72, pooled tirzepatide groups had mean reductions of 21.3% in body weight, 33.9% in fat mass and 10.9% in lean mass. Approximately three-quarters of the weight lost was fat and one-quarter was lean tissue; the proportions were broadly similar in the placebo group. [3]

The denominator is essential. “One-quarter of weight lost was lean mass” does not mean participants lost one-quarter of their starting muscle. It describes the composition of the weight change, not the fraction of original muscle that disappeared.

The study supports looking beyond total weight. It does not provide a universal personal ratio, nor should a DXA substudy be treated as a direct test of strength in every participant.

SEMALEAN: Less Lean Mass Did Not Mean Less Grip Strength

SEMALEAN followed patients with obesity receiving semaglutide over a year. Of 115 enrolled patients, 106 completed follow-up. Lean mass fell initially and then stabilized, while handgrip strength increased by an average of 4.5 kg at 12 months. [4]

This was a prospective observational study, not a randomized comparison proving that semaglutide itself increases strength. Nevertheless, the combination of findings is instructive: tissue quantity and function can move in different directions.

It would be equally inappropriate to conclude that all lean loss is harmless. The results encourage measuring function alongside composition, especially when the two appear to tell different stories.

Bimagrumab: Targeting the Activin Pathway

Bimagrumab is an antibody that targets type II activin receptors. BELIEVE tested it alone and with semaglutide in 507 adults without diabetes. The study assessed a 48-week treatment period followed by an open-label extension.

At week 48, the high-dose combination produced a mean weight reduction of 17.8 kg, versus 14.2 kg with semaglutide 2.4 mg. In the treatment-regimen analysis, fat accounted for 92.3% of weight loss with that combination versus 71.1% with semaglutide alone. Combination groups generally lost less lean mass. Muscle spasms, diarrhea and acne were among common events associated with bimagrumab. [5]

These findings support further testing of body-composition benefits. They do not establish that an investigational combination improves independence or prevents falls. The later extension also needs to be distinguished from the initial treatment period when quoting results.

Apitegromab: A Different Approach to Myostatin

Apitegromab selectively inhibits myostatin activation. The 24-week EMBRAZE phase 2 trial randomized 102 adults to tirzepatide plus apitegromab or placebo. The primary analysis used 87 participants who completed treatment and had evaluable scans.

Lean mass loss was 1.6 kg with apitegromab versus 3.5 kg with placebo: a 1.9 kg difference, with a reported 80% confidence interval of 1.2–2.7 kg. Total weight loss was similar. The exploratory physical-function assessments did not show notable between-group differences. [6]

The result supports proof of concept, not established long-term clinical benefit. Its small size, short duration, completer-based primary analysis and exploratory statistical framework matter. An 80% confidence interval should not be presented as if it were the more customary 95% interval.

Why These Studies Cannot Be Ranked by Headline Numbers

BELIEVE and EMBRAZE tested different drugs, background treatments, populations and durations. Their percentages and kilogram differences describe different endpoints. A larger number in one report is not a direct demonstration that its treatment is better.

For any future adjunct, the decision-relevant questions extend beyond a scan: Who benefits most? Is the effect sustained? Does it improve daily function? What additional adverse effects, treatment burden and cost does it introduce?

Exercise Evidence Already Extends Beyond the Scale

A randomized trial in adults aged 65 years or older with obesity compared exercise approaches during dietary weight loss. Combined aerobic and resistance training produced the greatest improvement in physical function among the exercise groups. Resistance training, alone or combined with aerobic activity, limited lean-mass loss compared with aerobic activity alone. [7]

This was not a trial of a modern GLP-1 medicine. It supplies relevant evidence about supporting function during weight loss, rather than a precise estimate of what a particular exercise programme adds to a particular drug.

The practical implication is to discuss a sustainable activity plan that fits existing ability and health conditions. A person starting from low activity, recovering from illness or living with joint pain may need a different progression and support from an experienced lifter.

Nutrition Support Is More Than a Protein Number

The 2025 joint advisory from four nutrition and obesity organizations recommends assessing dietary intake, strength and function and addressing inadequate nutrition during GLP-1 treatment. Adequate protein and resistance exercise are part of that approach, alongside management of gastrointestinal symptoms and broader dietary quality. [8]

A universal protein target is not the purpose of this article. Individual needs, medical conditions, appetite and food access affect what is appropriate and achievable. A clinician or registered dietitian can help turn general priorities into a workable plan.

The useful question is whether reduced appetite still allows adequate nourishment. An impressive weight trend should not distract from persistent difficulty eating or drinking enough, or from a routine that has become hard to maintain.

New Guidance Also Acknowledges Evidence Gaps

A 2026 EASO, EFAD and ECPO consensus discusses nutritional, functional and psychological support during incretin treatment. It emphasizes adequate protein, progressive resistance exercise and individualized care, while identifying gaps in long-term nutritional and musculoskeletal evidence. [9]

Consensus guidance helps clinicians act when direct trials are incomplete. It should be distinguished from a randomized study demonstrating one exact diet-and-exercise prescription for every patient.

Keep Proven Benefits in the Picture

Concern about muscle should be considered alongside established treatment benefits. In SELECT, semaglutide reduced major cardiovascular events in adults with established cardiovascular disease and overweight or obesity, without diabetes. [10]

That result belongs to the studied treatment and population. It neither proves that all lean-mass changes are unimportant nor establishes cardiovascular benefit for a muscle-directed add-on. It illustrates why a treatment assessment needs several outcomes, rather than a single scan or weight measurement.

What to Bring to a Follow-Up Appointment

A short, dated record can make a conversation more useful:

• Weight and measurements: show trends rather than an isolated reading.
• Everyday function: describe changes in usual walking, stairs or carrying tasks.
• Activity: note what you actually managed and what limited participation.
• Eating difficulties: record low appetite, symptoms or practical barriers that interfere with meals.
• Treatment history: include prescribed medication dates and clinician-directed changes.

Peptimize can help organize personal records for review. Such records provide context; they do not measure muscle directly or determine whether an experimental medicine is appropriate.

Readers following the research series can also explore retatrutide's multiple receptor activities and oral GLP-1 pharmacology with orforglipron. Muscle-preservation research asks a complementary question about the composition and consequences of weight change.

What Comes Next?

The next useful evidence will connect sustained body-composition changes with strength, mobility, safety and quality of life across broader populations. More lean tissue on a scan is an encouraging intermediate finding; its everyday value needs direct evaluation.

For now, the most informative account of progress includes fat loss, physical function, adequate nutrition and the person's own treatment goals. The scale remains useful, but it is one part of the story.

References

1. Morabia A, et al. BMI and DXA measurements of body composition. British Journal of Nutrition. 1999;82:49–55.
2. Cruz-Jentoft AJ, et al. Revised European consensus on sarcopenia. Age and Ageing. 2019;48:16–31.
3. Body-composition analysis of the SURMOUNT-1 tirzepatide trial. Diabetes, Obesity and Metabolism. 2025;27:2720–2729. doi:10.1111/dom.16275.
4. Alissou M, et al. SEMALEAN: semaglutide, body composition and muscle function. Diabetes, Obesity and Metabolism. 2026;28:112–121.
5. Heymsfield SB, et al. BELIEVE: bimagrumab and semaglutide in obesity. Nature Medicine. 2026;32:869–882.
6. Pratley RE, et al. EMBRAZE: apitegromab during tirzepatide-induced weight loss. Nature Medicine. 2026;32:2673–2678.
7. Villareal DT, et al. Aerobic and resistance exercise during weight loss in older adults. New England Journal of Medicine. 2017;376:1943–1955.
8. Mozaffarian D, et al. Joint advisory on nutritional priorities during GLP-1 treatment. 2025. doi:10.1177/15598276251344827.
9. EASO, EFAD and ECPO consensus on nutritional, functional and psychological care during incretin therapy. 2026.
10. Lincoff AM, et al. SELECT: semaglutide and cardiovascular outcomes in obesity. New England Journal of Medicine. 2023;389:2221–2232.

Medical Disclaimer

This article provides educational information and is not individual medical advice. The investigational combinations discussed are not established treatment protocols for preserving muscle during obesity care. Medication, nutrition and exercise decisions should be made with appropriately qualified professionals. Peptimize is a personal tracking tool and does not diagnose, prescribe or recommend treatment.