# Retatrutide Side Effects Observed in Clinical Trials | Doctor Retatrutide > Retatrutide side effects from Phase 2 and Phase 3 trials: nausea in up to 60% at 12 mg, heart rate increases, gallbladder events, kidney monitoring, and bone density surveillance. ## Retatrutide Side Effects Overview Retatrutide side effects reported in Phase 2 and Phase 3 trials are consistent with the GLP-1 receptor agonist drug class, with some unique signals attributable to the additional glucagon receptor component. The most common adverse events are gastrointestinal; the most significant signals under ongoing monitoring are heart rate elevation and thyroid C-cell surveillance. ## Gastrointestinal Side Effects: Frequency and Severity Gastrointestinal adverse events are the most common side effects reported in retatrutide trials. In the Phase 2 obesity trial, at the 12 mg dose, nausea was reported in up to 60% of participants, diarrhea in 15–33%, vomiting in 21–26%, and constipation in 14–18% [1]. The effects were generally characterized as mild to moderate in severity and most pronounced during the dose escalation phase rather than at steady-state maintenance dosing [1]. The trial protocol used gradual dose escalation specifically to reduce this burden, and most participants were able to continue to their target dose. A systematic review and meta-analysis confirmed that nausea risk was dose-dependent, with a risk ratio of 2.69 to 4.27 times placebo depending on dose [6]. Discontinuation due to gastrointestinal adverse events occurred in a subset of participants at higher doses; real-world discontinuation rates of 20–50% within the first year have been documented for the GLP-1 drug class broadly, though retatrutide-specific real-world data are not yet available given the compound's investigational status. ## Serious Adverse Events Reported in Retatrutide Trials Serious adverse events in Phase 2 retatrutide trials included serious gastrointestinal complications in a small subset of participants, elevated heart rate requiring monitoring, gallbladder disease including gallstones, and hypersensitivity reactions at higher doses [14]. An expert opinion review (Doggrell, 2023) noted that retatrutide's safety profile was consistent with GLP-1 class agents, with the glucagon receptor stimulation component still being defined at the time of Phase 1b completion [18]. The specific concern flagged was heart rate elevation — retatrutide increased mean heart rate by up to 6.7 beats per minute at higher doses, consistent with the known pharmacology of glucagon receptor agonism [14]. This heart rate signal, while modest, prompted the inclusion of TRIUMPH-Outcomes (NCT06383390) in the Phase 3 program, with MACE reduction and cardiovascular safety as its primary evaluation mandate [19]. ## Contraindications and Populations Excluded From Trials As an investigational drug, retatrutide does not yet have FDA-approved prescribing information with formal contraindications. The exclusion criteria applied across Phase 2 trials, which reflect standard GLP-1 class safety precautions, provide the closest available proxy. Phase 2 trials excluded participants with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2) — consistent with GLP-1 class precautions arising from rodent thyroid tumor signals seen in other GLP-1 agents [12]. Trials also excluded participants with prior pancreatitis, severe gastrointestinal disease, and active pregnancy [1, 3]. These exclusions reflect standard investigational drug clinical trial design and do not constitute approved labeling. When and if retatrutide receives FDA approval, a formal prescribing information document with contraindications, warnings, and precautions will be published. ## Organ-Level Safety: Gallbladder, Pancreas, and Kidneys Gallbladder events — including gallstones and acute cholecystitis — were reported in a subset of Phase 2 participants, consistent with the accelerated weight loss that is a known risk factor for gallstone formation and with GLP-1 class gallbladder effects [6]. Pancreatitis risk has been flagged as a class-level concern for GLP-1 receptor agonists. Retatrutide trials excluded participants with prior pancreatitis; Phase 3 monitoring includes pancreatic enzyme surveillance [12]. Kidney adverse events — primarily transient elevations in serum creatinine — were reported in a small subset of participants at the 12 mg dose in Phase 2 [9]. Post-hoc analysis confirmed that eGFR showed an initial transient decline followed by dose-dependent recovery to at or above baseline in obesity participants at 8–12 mg doses. The TRANSCEND-CKD Phase 2b trial is specifically designed to characterize renal safety and efficacy in chronic kidney disease patients [13]. ## Cardiovascular Monitoring: Heart Rate Effects Modest increases in mean heart rate — 2–5 bpm at lower doses, up to 6.7 bpm at the 12 mg dose — were observed in Phase 2 trials [14]. This signal is consistent with glucagon receptor agonism: glucagon has positive chronotropic effects in the cardiovascular system, and the GCGR activation component of retatrutide's triple mechanism is the likely driver. No serious arrhythmia events were reported in Phase 2 data. However, the signal is being actively monitored in TRIUMPH-Outcomes (NCT06383390), the Phase 3 cardiovascular outcomes trial designed to evaluate MACE reduction in high-cardiovascular-risk participants [19]. The [clinical trial references](/references) page lists the source publications for all cardiovascular monitoring data cited here. ## Does Retatrutide Cause Hair Loss? Telogen effluvium — a temporary form of stress-induced hair shedding — has been reported anecdotally among Phase 2 trial participants who experienced rapid significant weight loss [1]. This phenomenon is not specific to retatrutide's pharmacology. Telogen effluvium is a well-documented physiological response to any form of rapid significant weight loss, including that achieved through bariatric surgery, severe caloric restriction, or other pharmacological obesity treatments. The mechanism is physiological stress signaling in hair follicles triggered by sudden fat mass reduction rather than a direct drug effect [1]. No retatrutide-specific dermatological adverse event has been identified in the clinical literature. Hair shedding in this context typically resolves as weight stabilizes. ## Bone Density and Kidney Function Monitoring in Retatrutide Trials Bone mineral density monitoring was specified as a pre-determined TRIUMPH endpoint, following observations from rapid weight loss studies showing that significant fat mass reduction can accelerate bone loss — particularly in older adults [12]. Kidney adverse events — elevated serum creatinine — were reported in a small subset of Phase 2 participants at 12 mg [9]. Post-hoc analysis showed that eGFR showed a transient initial decrease followed by dose-dependent improvement to above baseline in the obesity cohort at 8–12 mg; however, individual variation at higher doses warrants monitoring, which TRIUMPH-Outcomes is designed to characterize [9, 19]. Thyroid C-cell surveillance — monitoring for thyroid tumors as seen in rodent studies with other GLP-1 agents — is an active Phase 3 endpoint. No human thyroid tumor signal has emerged from retatrutide Phase 2 data [12]. ## Long-Term Safety Profile: What the Evidence Shows Long-term safety data for retatrutide beyond 48 weeks are limited as of mid-2026. TRIUMPH extension cohorts are ongoing. Phase 2 open-label extensions published through early 2026 showed no new serious safety signals beyond those identified in the primary trials [18]. The evidence base for long-term safety monitoring of retatrutide is being built across the TRIUMPH program. Active Phase 3 surveillance endpoints include bone density, thyroid C-cell markers, gallbladder events, pancreatic enzyme changes, kidney function, and the cardiovascular outcomes measured in TRIUMPH-Outcomes [12, 19]. For full context on the known [gastrointestinal adverse events](/side-effects#gastrointestinal) and the [mechanism of action](/research#mechanism) driving both efficacy and the side effect profile, see the relevant sections on this site. --- A cinematic index of the Phase 2 and Phase 3 retatrutide trial record — primary sources only, no clinic, no prescription.