Muscle Preservation on GLP-1s: What UCN2, Amylin, and GIP Add for Body Recomp

This article previously linked its STEP 1 body-composition claim to an unrelated epilepsy paper, mixed trial populations and endpoints, and presented unsupported muscle-preservation comparisons. We corrected the references and results, distinguished lean tissue from muscle, and removed speculative treatment rankings and approval timelines.

Body recomposition describes a change in the balance of fat and lean tissue. Losing weight and preserving muscle strength are related goals, but a lower scale reading does not tell us how much skeletal muscle changed.

DXA scans estimate fat mass, bone mineral content, and lean soft tissue. Lean tissue includes muscle, organs, and water. A reduction in measured lean mass is therefore not equivalent to the same amount of skeletal muscle loss, and it does not by itself establish a decline in strength or physical function.

Published studies of semaglutide and tirzepatide show reductions in both fat and lean mass. Those findings make nutrition, physical activity, and functional assessment relevant to care. They do not establish that one drug is the best choice for muscle preservation in an individual patient.

The STEP 1 body-composition analysis included 140 participants: 95 receiving semaglutide 2.4 mg weekly and 45 receiving placebo, alongside lifestyle intervention. Participants had overweight or obesity without diabetes. The analysis measured changes over 68 weeks.

In the semaglutide group, body weight decreased by 15.0%, total fat mass by 19.3%, regional visceral fat mass by 27.4%, and total lean body mass by 9.7%, each relative to its own baseline. The proportion of body weight represented by lean mass increased by 3.0 percentage points because fat declined more.

These percentages have different denominators. A 9.7% reduction in starting lean mass does not mean that 9.7% of the weight lost was lean mass. This exploratory analysis also does not support the earlier claim in this article that every 40 pounds lost represents 30 pounds of fat and 10 pounds of muscle. It was a small substudy, reported as a conference abstract, and did not directly measure a corresponding loss of muscle strength.

The SURMOUNT-1 DXA substudy analyzed 160 participants with baseline and end-of-study scans: 124 receiving tirzepatide and 36 receiving placebo. The tirzepatide results pooled the 5, 10, and 15 mg doses; they were not results for the 15 mg group alone.

At 72 weeks, body weight, fat mass, and lean mass decreased by 21.3%, 33.9%, and 10.9%, respectively, in the pooled tirzepatide group. Approximately 75% of weight lost was fat mass and 25% was lean mass. The same approximate split appeared in the placebo group.

This study did not compare tirzepatide with semaglutide and did not isolate the effect of GIP receptor activation. It cannot establish that GIP directly spares muscle or that better gastrointestinal tolerability explains a superior body-composition result. Comparing these numbers with a different trial is useful context, but it is not a randomized comparison of muscle preservation.

The published retatrutide substudy evaluated adults with type 2 diabetes over 36 weeks in a Phase 2 trial. Of 189 people enrolled in the substudy, 103 completed treatment and had scans at both baseline and week 36. Its prespecified primary endpoint was change in total fat mass.

Retatrutide reduced fat mass compared with placebo and dulaglutide at the higher studied doses. The investigators reported that the proportion of lean mass lost relative to weight loss was similar to other obesity treatments.

That finding does not support this article's former claim that only 15–18% of retatrutide-associated weight loss is lean mass, or that a Phase 3 result proves superiority over semaglutide and tirzepatide for preserving muscle. Glucagon receptor activity is a mechanistic reason to investigate energy expenditure; it does not establish selective fat loss in humans. Treatment rankings and prescribing timelines cannot be inferred from that mechanism.

Cagrilintide is an amylin analogue studied with semaglutide as CagriSema. Weight-loss efficacy alone cannot establish whether adding amylin preserves skeletal muscle. The sources reviewed for this correction do not establish the muscle-preservation advantage previously asserted here. That question needs direct body-composition and functional evidence.

HM17321 is a UCN2 analogue targeting CRFR2. Hanmi announced its license agreement with Genentech on August 24, 2026, describing a development goal of weight loss with muscle preservation. Hanmi's preclinical poster reports animal findings relevant to that goal.

These are a company development claim and preclinical evidence, respectively. Neither establishes clinical benefit in humans, a reliable approval date, or a recommendation to switch treatment. Human trials need to assess safety, body composition, strength, and function.

Adequate nutrition and physical activity are part of maintaining muscle health. The ESPEN expert recommendations support protein intake alongside resistance and aerobic exercise in older adults. Their suggested protein ranges vary by health status; they are not a universal prescription for everyone using a GLP-1 medicine.

This article previously gave a rigid training and protein protocol, asserted that cardio does not preserve muscle, and suggested extending injection intervals or reducing doses to slow weight loss. Those recommendations exceeded the cited evidence. Nutrition, exercise, and medication adjustments should account for the person’s health, physical capacity, treatment indication, and prescriber’s advice.

Useful issues to discuss with a care team include difficulty eating enough, persistent gastrointestinal symptoms, loss of strength, and limitations in daily activities. Body-composition scans can add information, but functional changes and nutritional status matter alongside the scan results.

The cited studies do not establish that adding sermorelin, ipamorelin, CJC-1295, or MK-677 to GLP-1 therapy safely preserves muscle. Evidence that a compound changes growth hormone or IGF-1 does not establish improved strength or function during weight loss. Combining agents also creates safety questions that cannot be answered by studying each ingredient in isolation.

The evidence supports continued investigation of muscle preservation. It does not support a ranked treatment protocol built from receptor mechanisms and comparisons between unrelated trials.