Trevogrumab — Safety, Research, Risks & Legal Status

Not medical advice. Trevogrumab is discussed here for informational and harm-reduction purposes only. We do not endorse use, and any dosing context is informational, not a protocol.

Also known as	REGN1033; SAR391786
Category	Peptide (research chemical)
Developer	Regeneron Pharmaceuticals (with Sanofi collaboration; SAR391786 designation)
Antibody class	Fully human IgG4 monoclonal antibody
Target	GDF-8 (myostatin); sub-nanomolar affinity; no reported cross-reactivity with GDF-11
Development stage (mid-2026)	Phase 2 ongoing (COURAGE obesity trial, NCT06299098); Phase 2 completed in sarcopenia; Phase 1 completed
COURAGE interim finding	Prevented ~50% of semaglutide-induced lean mass loss in 26-week interim data; triplet arm (+ garetosmab) showed 40.9% muscle spasm rate
Sarcopenia Phase 2 result	Dose-dependent increase in total and appendicular lean body mass vs. placebo in adults ≥70 years; SAEs comparable to placebo (7.4% vs. 7.7%)
US legal status	Not FDA approved. Trevogrumab is an investigational drug accessible only through clinical trial enrollment in the United States. It is not approved for any indication and is not legally available for human use outside of a supervised clinical trial setting.

What is Trevogrumab?

Trevogrumab (REGN1033) is a fully human IgG4 monoclonal antibody developed by Regeneron Pharmaceuticals (with Sanofi collaboration) that specifically neutralizes myostatin (GDF-8), a TGF-beta superfamily protein that acts as a negative regulator of skeletal muscle growth. By blocking myostatin signaling, trevogrumab promotes lean muscle mass preservation and accretion. It is currently in Phase 2 clinical development, with its most advanced ongoing work in obesity in combination with GLP-1 receptor agonist therapy.

How it works

Trevogrumab binds mature myostatin (Growth Differentiation Factor 8, GDF-8) with sub-nanomolar affinity, neutralizing its inhibitory signaling on skeletal muscle. Myostatin normally restrains muscle hypertrophy; blockade releases this brake and allows net muscle protein accretion. The antibody is reported to have no cross-reactivity with GDF-11, a closely related TGF-beta family member. The mechanism is consistent with the most commonly observed adverse event - muscle spasm - which is thought to reflect enhanced muscle contractility downstream of pathway blockade. In combination studies, trevogrumab has been co-administered with garetosmab (anti-activin A) to achieve broader inhibition of the TGF-beta pathway's negative regulators of muscle.

Background & history

Regeneron initiated Phase 1 trials of REGN1033 around 2012, including studies in healthy volunteers and postmenopausal women. Phase 2 sarcopenia studies (e.g., NCT01963598) enrolled approximately 250 older adults (mean age 78) through the 2012-2015 period, demonstrating dose-dependent increases in lean mass by DEXA. A 2020 Phase 1 study in postmenopausal women (NCT02943239, n=82) evaluated IV dosing alone and in combination with garetosmab, showing sustained biomarker elevation and modest thigh muscle volume gains. As of mid-2026, the compound's most active development front is the Phase 2 COURAGE trial (NCT06299098) in obesity, evaluating trevogrumab as an adjunct to semaglutide to mitigate GLP-1-associated lean mass loss. Collaborative development with Sanofi produced the SAR391786 designation.

What the research says

Human clinical data exist but remain Phase 1-2 only with no approved indication. Phase 1 (NCT02943239): 82 postmenopausal women; single 6 mg/kg IV dose produced approximately 4.6% thigh muscle volume increase vs. placebo; combination with garetosmab reached 7.7%; sustained myostatin biomarker elevation approximately 8 weeks post-dose. Phase 2 sarcopenia (NCT01963598): 250 older adults, 3-month subcutaneous dosing; dose-dependent increase in total and appendicular lean body mass by DEXA; serious adverse event rates comparable between REGN1033 groups (7.4%) and placebo (7.7%). Phase 2 COURAGE trial (NCT06299098): 999 patients with obesity, 26-week interim data presented at EASD; co-administration with semaglutide prevented approximately 50% of semaglutide-induced lean mass loss while enhancing fat loss; approximately 35% of semaglutide-induced total weight loss was lean mass in monotherapy arms, substantially reduced in combination. No Phase 3 data exist as of mid-2026. Long-term efficacy, functional outcomes, and effects on hard clinical endpoints such as fracture or mortality have not been established in published trials.

Reported effects

Dose-dependent increase in lean body mass (DEXA) in older adults with sarcopenia - Phase 2 human data
Preservation of lean mass during GLP-1-induced weight loss - Phase 2 interim human data (COURAGE trial)
Thigh muscle volume increase (~4.6% monotherapy, ~7.7% in combination with garetosmab) - Phase 1 human data in postmenopausal women
Sustained suppression of circulating myostatin biomarkers for approximately 8 weeks after single IV dose - Phase 1 human data
Enhanced fat loss when combined with semaglutide - Phase 2 interim data; magnitude and durability not yet fully characterized
No effects on GDF-11 signaling reported - selectivity data from preclinical characterization

Dosing & administration (informational)

Published trial ranges include single IV doses of 6 mg/kg (Phase 1 in postmenopausal women) and multi-dose subcutaneous regimens evaluated over 3 months in sarcopenia studies. Specific doses and schedules in the COURAGE obesity trial have not been fully published as of mid-2026. These ranges are reported for informational and scientific reference only and do not constitute a dosing protocol. This compound has no approved human dosing. Consult a licensed clinician and appropriate clinical trial resources for any patient-facing questions.

This is general research/context information, not medical advice or a recommended protocol.

Safety & side effects

Most common adverse event: muscle spasm (4.6-9.3% in dual therapy arms; 40.9% in triplet combination with semaglutide + garetosmab) - Phase 2 human data
Other AEs reported at ≥5%: nausea, constipation, fatigue, diarrhea, headache, upper respiratory and nasopharyngeal infections
Severity: predominantly mild-to-moderate in dual therapy arms
Treatment discontinuation rate substantially higher in triple combination arm (~30.9%) versus dual therapy (~4.6-4.7%) - important tolerability signal for triplet regimen
Serious adverse event rate comparable to placebo in sarcopenia Phase 2 (7.4% vs. 7.7%)
Long-term safety unknown; no Phase 3 data; no data on cardiovascular outcomes, bone effects, or safety beyond 26 weeks in large populations
Not approved; no post-marketing safety data exist

Drug & supplement interactions

N
o
f
o
r
m
a
l
d
r
u
g
i
n
t
e
r
a
c
t
i
o
n
s
t
u
d
i
e
s
h
a
v
e
b
e
e
n
p
u
b
l
i
s
h
e
d
i
n
t
h
e
o
p
e
n
l
i
t
e
r
a
t
u
r
e
a
s
o
f
m
i
d
-
2
0
2
6
.
C
O
U
R
A
G
E
t
r
i
a
l
d
a
t
a
i
n
v
o
l
v
e
d
e
l
i
b
e
r
a
t
e
c
o
-
a
d
m
i
n
i
s
t
r
a
t
i
o
n
w
i
t
h
s
e
m
a
g
l
u
t
i
d
e
(
G
L
P
-
1
r
e
c
e
p
t
o
r
a
g
o
n
i
s
t
)
a
n
d
,
i
n
a
t
r
i
p
l
e
t
a
r
m
,
g
a
r
e
t
o
s
m
a
b
(
a
n
t
i
-
a
c
t
i
v
i
n
A
)
;
t
h
e
t
r
i
p
l
e
t
c
o
m
b
i
n
a
t
i
o
n
p
r
o
d
u
c
e
d
s
u
b
s
t
a
n
t
i
a
l
l
y
h
i
g
h
e
r
r
a
t
e
s
o
f
m
u
s
c
l
e
s
p
a
s
m
a
n
d
t
r
e
a
t
m
e
n
t
d
i
s
c
o
n
t
i
n
u
a
t
i
o
n
,
i
n
d
i
c
a
t
i
n
g
p
h
a
r
m
a
c
o
d
y
n
a
m
i
c
i
n
t
e
r
a
c
t
i
o
n
.
B
r
o
a
d
T
G
F
-
b
e
t
a
p
a
t
h
w
a
y
m
o
d
u
l
a
t
i
o
n
f
r
o
m
c
o
m
b
i
n
a
t
i
o
n
b
i
o
l
o
g
i
c
s
s
h
o
u
l
d
b
e
c
o
n
s
i
d
e
r
e
d
a
p
o
t
e
n
t
i
a
l
s
o
u
r
c
e
o
f
a
d
d
i
t
i
v
e
o
r
u
n
p
r
e
d
i
c
t
a
b
l
e
m
u
s
c
u
l
o
s
k
e
l
e
t
a
l
e
f
f
e
c
t
s
.
N
o
d
a
t
a
o
n
i
n
t
e
r
a
c
t
i
o
n
s
w
i
t
h
i
m
m
u
n
o
s
u
p
p
r
e
s
s
a
n
t
s
,
o
t
h
e
r
a
n
a
b
o
l
i
c
a
g
e
n
t
s
,
o
r
s
m
a
l
l
m
o
l
e
c
u
l
e
s
a
r
e
a
v
a
i
l
a
b
l
e
i
n
t
h
e
p
u
b
l
i
c
l
i
t
e
r
a
t
u
r
e
.

Who should avoid it

Use outside an approved clinical trial - not legally permissible and safety in uncontrolled settings is unknown
Combination with activin A antagonists (e.g., garetosmab) except under clinical trial supervision - triplet regimen showed 40.9% muscle spasm rate and ~31% discontinuation
Self-administration of any product sold as trevogrumab outside a trial - no legitimate commercial supply exists and identity/purity cannot be verified
Use in pregnancy or lactation - no safety data exist in these populations

How it is commonly combined

No evidence-based stacking guidance exists. COURAGE trial co-administration with semaglutide is the only published human combination studied in a controlled setting, and that combination is investigational. The triplet addition of garetosmab to semaglutide plus trevogrumab produced substantially worse tolerability in interim COURAGE data. No other combination data in humans are publicly available.

Legal & regulatory. Not FDA approved. Trevogrumab is an investigational drug accessible only through clinical trial enrollment in the United States. It is not approved for any indication and is not legally available for human use outside of a supervised clinical trial setting.

Quality & harm reduction

Safer, legal alternative we recommend

Creatine Supreme. For supporting muscle mass and strength, creatine monohydrate is the most evidence-backed legal option, with decades of safety data - ours ships from the Peptropix line.

See our recommended pick

Find Trevogrumab →

Know your numbers before you research

Order your own bloodwork online — hormone, metabolic and inflammation panels, no doctor visit needed. Know your baselines before and during any protocol. Independent bloodwork is the cheapest insurance there is.

Get tested with Ulta Lab Tests →

Frequently asked questions

What is trevogrumab being developed for?

Two primary indications have been studied in human trials: sarcopenia (age-related muscle loss in older adults) and, more recently, the preservation of lean muscle mass during GLP-1 receptor agonist-induced weight loss in people with obesity. The COURAGE trial (NCT06299098) is the active ongoing Phase 2 study and is focused on the obesity/semaglutide combination use case.

How does trevogrumab differ from other myostatin inhibitors?

Trevogrumab is a fully human IgG4 antibody with reported selectivity for GDF-8 (myostatin) and no published cross-reactivity with GDF-11. Other approaches in the myostatin inhibitor class (follistatin gene therapy, bimagrumab, apitegromab, landogrozumab) use different antibody formats, target different epitopes, or have broader TGF-beta pathway coverage. Head-to-head comparisons in humans are not available in the public literature.

Can I obtain trevogrumab for personal use?

No. Trevogrumab is an unapproved investigational drug. There is no legal commercial supply. Access is limited to enrollment in a qualifying clinical trial. Any product sold as trevogrumab outside of a trial cannot be verified for identity or purity.

What dose should I take?

Dosing guidance for personal use is outside the scope of this reference. Trevogrumab has no approved dosing regimen and is available only in clinical trials where dosing is determined by the study protocol and overseen by clinicians. Consult a licensed physician and ClinicalTrials.gov (search REGN1033 or NCT06299098) if you are interested in trial eligibility.

What are the most important safety signals from existing trials?

Muscle spasm is the most commonly reported adverse event, occurring in 4.6-9.3% of participants in dual-therapy arms and rising sharply to 40.9% in the triplet combination arm (semaglutide + trevogrumab + garetosmab) in COURAGE interim data. Treatment discontinuation in the triplet arm was approximately 30.9% versus 4.6-4.7% in dual-therapy arms. Serious adverse event rates in the sarcopenia Phase 2 were comparable to placebo. Long-term safety beyond 26 weeks in large populations is unknown.

What is the current regulatory status?

Trevogrumab is not approved by the FDA or any other major regulatory agency as of mid-2026. It remains an investigational new drug in Phase 2 clinical development. No approval timeline has been announced publicly.

References & further reading

ClinicalTrials.gov: NCT02943239 (Phase 1, GDF8 and activin A, postmenopausal women)
ClinicalTrials.gov: NCT01963598 (Phase 2, sarcopenia, older adults)
ClinicalTrials.gov: NCT06299098 (Phase 2, COURAGE obesity trial, semaglutide combination)
PubMed: search 'GDF8 activin A negative regulators muscle mass postmenopausal trevogrumab REGN1033' - see PMC12075688
PubMed: search 'trevogrumab myostatin REGN1033 lean mass EASD 2025' for conference presentation data