Investigational · not FDA approved
Editorially reviewed · Last updated July 23, 2026 · How we review
Part of Safety Topics.
Key findings
- The most common retatrutide side effects are gastrointestinal — nausea, vomiting, diarrhea, and constipation — consistent with the broader GLP-1 class.
- GI side effects are usually mild to moderate, occur most often during dose escalation, and typically improve with time and slow titration.
- Dysesthesia (abnormal skin sensations) was not reported in Phase 2. It emerged in Phase 3 TRIUMPH-4 as a dose-dependent signal — 8.8% at 9 mg and 20.9% at 12 mg, versus 0.7% on placebo — and has not been a notable finding with semaglutide or tirzepatide.
- In TRIUMPH-4, adverse events led to discontinuation in 12.2% of the 9 mg arm and 18.2% of the 12 mg arm, versus 4.0% on placebo.
- Lean-mass loss accompanies about 25–40% of total weight lost on GLP-1 class drugs, including retatrutide — protein intake and resistance training are the main mitigations.
- Long-term cardiovascular, renal, and cancer safety data will come from TRIUMPH-Outcomes (NCT06383390; multi-year CVOT).
Retatrutide Side Effects & Safety
This is the full safety page for retatrutide side effects (also searched as reta side effects or GLP-3 side effects). Retatrutide (LY3437943), known informally as "GLP-3" (retatrutide), is an investigational triple-agonist weight-loss drug. Like other drugs in the GLP-1 class, the most common adverse events are gastrointestinal — nausea, diarrhea, constipation, and vomiting — usually mild to moderate and concentrated during dose escalation.
For diet tactics that reduce GI symptoms (shot-day soft foods, fiber ramp when constipated, protein when you cannot eat), see What to eat on reta and the protein target calculator. This page is the rates-and-risks reference: trial incidence, the dysesthesia signal, and class-level concerns.
The most complete published Phase 3 adverse-event tables so far come from the TRIUMPH-4 trial (445 adults with obesity and knee osteoarthritis, 68 weeks). Phase 2 (NEJM 2023) supplies supporting detail on heart rate, lipids, and rare events. Full safety for the broader TRIUMPH program will keep updating as remaining readouts post.
Retatrutide has not been approved by the FDA. Numbers below are trial means under protocol conditions — not a personal risk prediction.
Most Common Side Effects at a Glance
The most common side effects of retatrutide at the 12 mg dose, based on TRIUMPH-4 Phase 3 trial data (445 participants over 68 weeks):
- Nausea — 43.2% (vs. 10.7% placebo)
- Diarrhea — 33.1% (vs. 13.4% placebo)
- Constipation — 25.0% (vs. 8.7% placebo)
- Vomiting — 20.9% (vs. 0.0% placebo)
- Dysesthesia (abnormal skin sensation) — 20.9% (vs. 0.7% placebo)
- Decreased appetite — 18.2% (vs. 9.4% placebo)
Gastrointestinal symptoms (nausea, diarrhea, constipation, vomiting) are the most common, generally mild-to-moderate, and concentrated during dose escalation. Dysesthesia is the new signal unique to retatrutide — it was not reported with semaglutide or tirzepatide. See the dysesthesia section for details.
Discontinuation rates due to adverse events: 12.2% at 9 mg, 18.2% at 12 mg, 4.0% on placebo.
Side Effect Rates from TRIUMPH-4
The TRIUMPH-4 trial (announced December 2025) tested retatrutide at 9mg and 12mg doses against placebo over 68 weeks in 445 adults with obesity and knee osteoarthritis. The most commonly reported adverse events were:
| Adverse Event | 9mg | 12mg | Placebo |
|---|---|---|---|
| Nausea | 38.1% | 43.2% | 10.7% |
| Diarrhea | 34.7% | 33.1% | 13.4% |
| Constipation | 21.8% | 25.0% | 8.7% |
| Vomiting | 20.4% | 20.9% | 0.0% |
| Decreased appetite | 19.0% | 18.2% | 9.4% |
| Dysesthesia | 8.8% | 20.9% | 0.7% |
Discontinuation rates due to adverse events: 12.2% at 9mg, 18.2% at 12mg, and 4.0% for placebo. Eli Lilly noted that some discontinuations were attributed to "perceived excessive weight loss" rather than intolerable side effects.
There was no significant increase in serious adverse events between the retatrutide groups and the placebo group.
Gastrointestinal Side Effects
The most common side effects of retatrutide — nausea, diarrhea, constipation, and vomiting — are gastrointestinal (GI) in nature. This is consistent with the entire GLP-1 drug class. GLP-1 receptor activation slows gastric emptying (the rate at which food leaves the stomach), which is central to the drug's appetite-reducing mechanism but also the primary driver of GI symptoms.
Nausea
Nausea was the most frequently reported side effect in TRIUMPH-4, affecting 43.2% of participants at the 12mg dose compared to 10.7% on placebo. Nausea is typically most pronounced during the dose-escalation phase and tends to diminish as the body adjusts to the drug.
Diarrhea
Diarrhea affected approximately one-third of participants at both the 9mg (34.7%) and 12mg (33.1%) doses. This is consistent with rates seen in trials of other GLP-1 drugs and is generally classified as mild to moderate.
Constipation
Constipation occurred in 21.8% (9mg) to 25.0% (12mg) of participants, compared to 8.7% on placebo. Slowed gastric emptying can reduce bowel motility, which contributes to constipation. It may seem contradictory that retatrutide causes both diarrhea and constipation, but different individuals respond differently, and the same person may experience both at different points during treatment.
Vomiting
Vomiting was reported in approximately 20% of participants at both active doses and 0% on placebo. Like nausea, vomiting is more common during dose escalation and tends to improve over time.
Decreased Appetite
Decreased appetite — reported in 18-19% of active-dose participants — is technically a side effect, but also one of the drug's primary mechanisms of action. The distinction matters: in clinical trial reporting, any physiological change that participants report is listed as an adverse event, even when it is the intended therapeutic effect.
Dysesthesia: A New Safety Signal
One finding in TRIUMPH-4 that drew particular attention was dysesthesia — a condition in which normal sensations feel unusual or painful. This could include tingling, burning, numbness, or a heightened sensitivity to touch.
What the data shows
- Dysesthesia was reported in 20.9% of participants at 12mg, 8.8% at 9mg, and just 0.7% on placebo
- The effect is clearly dose-dependent — more than doubling from the 9mg to 12mg dose
- It was described as mild in most cases and rarely led to discontinuation
- It was not reported in retatrutide's Phase 2 trials, making it a new finding that emerged only in the larger, longer Phase 3 study
Why it matters
Dysesthesia can be a symptom of nerve-related conditions such as diabetic neuropathy or multiple sclerosis. In the context of retatrutide, the mechanism behind it is not yet understood. It is unclear whether retatrutide directly affects peripheral nerves, whether the symptom is related to rapid weight loss, or whether some other mechanism is involved.
BMO Capital Markets flagged dysesthesia as a signal worth monitoring in future TRIUMPH program readouts. Whether this finding becomes a significant safety concern or remains a mild, manageable effect will depend on data from the remaining Phase 3 trials and any long-term follow-up studies.
What we don't know about dysesthesia
- Whether symptoms resolve after stopping retatrutide
- Whether specific populations (people with diabetes, neuropathy, or other conditions) are at higher risk
- The underlying mechanism by which retatrutide might cause abnormal nerve sensations
- Whether this effect is unique to retatrutide or could emerge with other triple agonists
Dose-Dependent Side Effects and Titration
Side effects in TRIUMPH-4 were generally dose-dependent — more common and more frequent at 12mg than at 9mg. This pattern is consistent across the GLP-1 drug class: higher doses produce greater efficacy but also more side effects.
The titration schedule
To manage this, retatrutide uses a gradual titration schedule:
- Start at 2mg once weekly
- Increase the dose every 4 weeks in stepwise increments
- Reach the target dose (9mg or 12mg) over several months
This slow escalation gives the body time to adapt to each dose level. Most GI side effects — nausea, vomiting, diarrhea — are concentrated during the early weeks of each dose increase and tend to subside as the body adjusts.
Why titration matters
Without titration, starting directly at a high dose would cause severe GI symptoms in most patients. The titration strategy is the same one used for semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound), and it is a major reason why GI side effects in clinical trials, while common, are generally classified as mild to moderate and tolerable for the majority of participants.
How Side Effects Compare to Ozempic and Mounjaro
Retatrutide's GI profile is broadly similar to other incretin drugs. Cross-trial nausea rates from the landmark obesity programs:
| Drug | Dose | Trial | Nausea Rate | Notes |
|---|---|---|---|---|
| Semaglutide (Wegovy) | 2.4mg | STEP 1 | ~44% | GI class pattern; no dysesthesia signal of note |
| Tirzepatide (Zepbound) | 15mg | SURMOUNT-1 | ~31% | Dual agonist; lower nausea than STEP 1 in that program |
| Retatrutide | 12mg | TRIUMPH-4 | ~43% | Plus dysesthesia 20.9% at 12mg (dose-dependent) |
Adding the glucagon receptor does not clearly explode GI rates versus semaglutide in these separate programs. Retatrutide's 12mg nausea rate is close to STEP 1 and higher than SURMOUNT-1's top dose.
However, cross-trial comparisons should be interpreted with caution. These trials had different patient populations, study designs, and duration. Only head-to-head trials can definitively compare safety profiles, and none have been published comparing retatrutide directly to semaglutide or tirzepatide.
The new signal to watch is dysesthesia, which has not been reported as a significant finding in semaglutide or tirzepatide trials.
For a detailed comparison of retatrutide versus existing drugs, see Retatrutide vs Mounjaro vs Ozempic.
Cardiovascular Effects
TRIUMPH-4 reported several positive cardiovascular outcomes in the retatrutide groups:
- Systolic blood pressure reduced by 14.0 mmHg at the 12mg dose
- Improvements in non-HDL cholesterol, triglycerides, and hsCRP (a marker of systemic inflammation)
These cardiometabolic benefits are consistent with effects seen across the GLP-1 drug class and are likely driven by a combination of weight loss and direct metabolic effects of the drug. Semaglutide has already demonstrated cardiovascular risk reduction in the SELECT trial, and whether retatrutide offers similar or greater cardiovascular protection is a question that dedicated cardiovascular outcome trials would need to answer.
In the Phase 2 trial, the blood pressure improvements were large enough that 41% of participants in the combined 8 mg group and 30% in the 12 mg group discontinued at least one antihypertensive medication during the 48-week study (NEJM 2023).
Heart rate
Heart rate increased on retatrutide in a dose-dependent manner — a pattern shared with other drugs that activate the GLP-1 receptor. In the Phase 2 trial, the increase peaked at 24 weeks and then declined at 36 and 48 weeks, and the magnitude was "similar to those reported for GLP-1 receptor agonists" (NEJM 2023). Reported cardiac arrhythmias were mild to moderate, with one exception: a single severe adverse event of prolonged QT syndrome occurred in a participant who was also taking ondansetron — a medication independently known to prolong the QT interval. If you take medications that prolong the QT interval (some antiemetics, antibiotics, antipsychotics, antidepressants) or have a history of arrhythmia, discuss heart-rate and rhythm monitoring with your prescriber before starting any incretin therapy.
Class-Level Safety Concerns
Retatrutide belongs to the GLP-1 receptor agonist class, and several safety concerns apply broadly to drugs in this category. These have not been specifically flagged as problems in retatrutide trials, but they warrant awareness.
Thyroid cancer risk
All GLP-1 receptor agonists carry a boxed warning about the risk of medullary thyroid carcinoma (MTC). This warning is based on findings in rodent studies where GLP-1 drugs caused thyroid C-cell tumors. Whether this translates to humans remains an open question — recent epidemiological evidence suggests that GLP-1 drugs are not associated with increased thyroid cancer risk in humans, but longer-term data and more studies are needed. People with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) should not use GLP-1 drugs.
Gallbladder events
GLP-1 drugs have been associated with an increased incidence of gallbladder-related events, including gallstones and cholecystitis (inflammation of the gallbladder). Rapid weight loss itself is a known risk factor for gallstones. This has not been specifically flagged in retatrutide trial data, but it remains a theoretical risk given the class association and the significant amount of weight loss retatrutide produces.
Pancreatitis
Pancreatitis (inflammation of the pancreas) has been identified as a potential risk with GLP-1 drugs generally. While the absolute risk appears to be low, patients are typically monitored for symptoms such as severe abdominal pain. The retatrutide Phase 2 trial did not report pancreatitis as a significant finding, but the sample sizes in trials to date have been relatively small.
Gastroparesis
Gastroparesis — delayed or absent stomach emptying — is a class-level concern because slowed gastric emptying is part of how GLP-1 drugs work. A 2023 JAMA cohort study of patients using GLP-1 agonists for weight loss quantified the real-world risk:
| Drug | Gastroparesis incidence (per 1,000 person-years) | Adjusted HR vs. bupropion-naltrexone |
|---|---|---|
| Semaglutide | 9.1 | 3.31 (95% CI 1.04-10.50) |
| Liraglutide | 7.3 | 3.67 (95% CI 1.15-11.90) |
| Bupropion-naltrexone | 3.1 | 1 (reference) |
For retatrutide specifically, the Phase 2 NEJM trial reported nausea in up to 60% and vomiting in up to 26% of participants at 12 mg but did not list gastroparesis as a separately captured adverse event. The "severe gastrointestinal adverse event" category was reported in approximately 6% of the 12-mg group and 0% of the placebo group, but the trial did not break this down by diagnosis.
Warning signs that should prompt clinical evaluation include persistent vomiting that does not improve as the body adapts to a given dose, inability to keep down food or fluids, severe abdominal pain or bloating, or GI symptoms that continue between weekly doses rather than concentrating in the day or two after each injection.
Muscle and Bone Considerations
A persistent concern with all weight loss interventions — drugs, surgery, or caloric restriction — is the loss of lean body mass (muscle) alongside fat. When the body loses a substantial amount of weight, some of that loss inevitably comes from muscle tissue, not just fat.
What we know
- All GLP-1 drugs cause some degree of lean mass loss alongside fat loss. In semaglutide trials, approximately 40% of weight lost was lean mass in some analyses.
- Retatrutide's glucagon receptor activation is hypothesized to have muscle-sparing properties. Glucagon promotes lipolysis (fat breakdown) and thermogenesis (increased energy expenditure), which could theoretically shift the body's energy sourcing toward fat rather than muscle. However, this hypothesis has not been confirmed with body composition data from Phase 3 trials.
- No published retatrutide trial has reported detailed body composition analysis (e.g., DEXA scans) distinguishing fat loss from lean mass loss.
What we don't know
- Whether retatrutide's triple-agonist mechanism results in a better fat-to-lean-mass loss ratio than semaglutide or tirzepatide
- Long-term effects on bone mineral density, which can decline with significant weight loss
- Whether resistance training during retatrutide treatment meaningfully preserves lean mass (this is the standard clinical recommendation for all weight loss interventions, but has not been specifically studied in retatrutide trials)
What We Don't Know Yet
Retatrutide is still in clinical development. While TRIUMPH-4 provides the best safety data available, there are significant gaps in our knowledge:
- Long-term safety beyond 68 weeks: TRIUMPH-4 is the longest published trial. We do not know what happens with years of continuous use, which is the likely treatment duration for a chronic obesity medication.
- Safety in larger populations: TRIUMPH-4 enrolled only 445 participants. Rare side effects — those occurring in fewer than 1 in 100 or 1 in 1,000 people — may not appear until the drug is used by thousands or millions of patients.
- Dysesthesia resolution: It is unknown whether the abnormal nerve sensations seen in TRIUMPH-4 resolve after stopping the drug, persist, or progress.
- Drug interactions: Retatrutide's interactions with other medications have not been extensively characterized. Since it slows gastric emptying, it could theoretically affect the absorption of oral medications.
- Specific populations: Safety data in pregnant or breastfeeding women, elderly patients (over 75), adolescents, and people with severe kidney or liver disease is limited or nonexistent.
- Weight regain after stopping: Like other GLP-1 drugs, weight regain after discontinuation is expected, but the rate and extent are not yet characterized for retatrutide.
These gaps will begin to close as additional TRIUMPH program trials report results throughout 2026 and as the FDA conducts its own review of the complete safety database. For the latest trial results and timeline updates, see Clinical Trials & Results and FDA Approval Timeline.
Frequently Asked Questions
Is retatrutide safe?
Based on Phase 3 clinical trial data, retatrutide's safety profile is broadly consistent with other GLP-1 drugs that are already FDA-approved (semaglutide, tirzepatide). There was no significant increase in serious adverse events compared to placebo in the TRIUMPH-4 trial. However, retatrutide has not been approved by the FDA, and the full safety profile is not yet established. Clinical trials have relatively small sample sizes and limited duration. Only FDA review and post-market surveillance after approval can provide a more complete picture of a drug's safety.
What are the side effects of retatrutide?
The most common retatrutide side effects in the TRIUMPH-4 Phase 3 trial (12mg, 68 weeks) were nausea (43.2%), diarrhea (33.1%), constipation (25.0%), vomiting (20.9%), dysesthesia (20.9%), and decreased appetite (18.2%). GI events are usually mild to moderate and peak during dose escalation. Discontinuation for adverse events was 18.2% at 12mg vs 4.0% on placebo. Full tables are in Side Effect Rates from TRIUMPH-4. Retatrutide is investigational and not FDA-approved.
What are reta side effects?
"Reta" is shorthand for retatrutide. Reta side effects are the same trial-listed adverse events — predominantly GI symptoms plus the dose-dependent dysesthesia signal. See Most Common Side Effects at a Glance.
What is dysesthesia?
Dysesthesia is a condition in which normal sensations feel unusual, uncomfortable, or painful. It can manifest as tingling, burning, numbness, or abnormal sensitivity to touch. In the TRIUMPH-4 trial, dysesthesia was reported in 20.9% of participants at the 12mg dose, compared to 0.7% on placebo. It was generally described as mild and rarely led to treatment discontinuation. The mechanism by which retatrutide might cause dysesthesia is not yet understood, and this signal was not observed in Phase 2 trials. It is a new finding that researchers and analysts are monitoring closely. See the dysesthesia section above for full details.
Does retatrutide cause muscle loss?
All weight loss — whether from drugs, surgery, or diet — involves some degree of lean mass loss alongside fat loss. This is not unique to retatrutide. There is a theoretical reason to believe retatrutide may be somewhat better at preserving muscle than other GLP-1 drugs: its glucagon receptor activation promotes fat breakdown and energy expenditure, which could shift the body's energy sourcing toward fat rather than muscle. However, this hypothesis has not been confirmed with published body composition data from retatrutide trials. If you are considering any weight loss medication, the standard clinical recommendation is to combine treatment with resistance training and adequate protein intake to preserve lean mass. See Does retatrutide cause muscle loss? for the DXA data, and the protein target calculator plus what to eat on reta for how to hit a protein floor when appetite is broken.
Are retatrutide side effects worse than Ozempic?
Based on available trial data, retatrutide's side effects are comparable to, not dramatically worse than, those of semaglutide (Ozempic/Wegovy). Nausea rates are similar (~43% for retatrutide 12mg vs. ~44% for semaglutide 2.4mg). Other GI side effects — diarrhea, constipation, vomiting — follow similar patterns across both drugs. The key difference is dysesthesia, which was reported at a notable rate with retatrutide (20.9% at 12mg) and has not been a significant finding in semaglutide trials. It is important to note that cross-trial comparisons have limitations — only a head-to-head trial can provide a definitive comparison. See Retatrutide vs Mounjaro vs Ozempic for a broader comparison.
How common is gastroparesis on retatrutide?
Retatrutide trials have not reported gastroparesis as a separately captured adverse event. The Phase 2 NEJM publication documented "severe gastrointestinal" events in approximately 6% of the 12-mg group and 0% in the placebo group, but did not break that category down by diagnosis. For the broader GLP-1 class, a 2023 JAMA cohort study reported gastroparesis incidence of 9.1 per 1,000 person-years for semaglutide users and 7.3 per 1,000 for liraglutide users, versus 3.1 for bupropion-naltrexone — an adjusted hazard ratio of roughly 3.3-3.7 for the GLP-1 drugs. Whether retatrutide's gastroparesis rate will be higher, lower, or similar to GLP-1-only drugs has not been established.
How can I reduce the risk of gallstones on retatrutide?
Rapid weight loss is a known risk factor for gallstones. According to the NIDDK, when you lose weight quickly or go for long periods without eating, the liver releases extra cholesterol into bile and the gallbladder may not empty properly — both of which promote stone formation. Retatrutide has not been specifically studied for gallstone risk, but the general strategies clinicians use during rapid weight loss apply: aim for a slower, steady pace (experts suggest losing 5 to 10 percent of body weight over about 6 months), avoid skipping meals or prolonged fasting, and stay physically active. For people losing weight rapidly through very-low-calorie diets or bariatric surgery, the medication ursodiol (ursodeoxycholic acid) can help prevent gallstones; whether it has a role alongside a GLP-1-class drug is a question for your doctor. See the Gallbladder events section above for the underlying class data.
Can retatrutide cause hair loss?
Retatrutide's own clinical trials have not reported hair loss (alopecia) as an adverse event — it does not appear in the TRIUMPH-4 side-effect data above. However, hair loss is a recognized signal across the GLP-1 drug class. In the tirzepatide obesity trial (SURMOUNT-1), alopecia was reported in roughly 5% of participants (5.1%, 5.3%, and 4.9% at the 5mg, 10mg, and 15mg doses) versus 0.9% on placebo. A 2025 systematic review found the signal tracks the amount of weight lost more than the specific drug: in the Wegovy (semaglutide) program, 5.3% of people who lost more than 20% of their body weight reported hair loss, compared with 2.5% of those who lost less than 20%. That pattern is consistent with telogen effluvium — a temporary, reversible shedding triggered by the metabolic stress of rapid weight loss — rather than the drug directly damaging hair follicles. Because retatrutide produces the largest weight loss in the class (roughly 24 to 29% at the highest doses), the same weight-loss-driven shedding is at least as relevant for retatrutide, even though it has not been separately measured. Telogen effluvium typically resolves on its own once weight stabilizes, and adequate protein intake is the standard supportive measure. Sudden, patchy, or persistent shedding is worth raising with a clinician to rule out other causes.
Does retatrutide raise your heart rate?
In the Phase 2 obesity trial, heart rate increased on retatrutide in a dose-dependent way, peaked at 24 weeks, and then declined at 36 and 48 weeks. The size of the increase was similar to what has been reported for GLP-1 receptor agonists like semaglutide (NEJM 2023). The trial's main paper does not list per-dose bpm changes — those numbers are in supplementary tables. No clinically significant arrhythmias were observed apart from one prolonged-QT event in a participant also taking ondansetron, a drug independently known to prolong the QT interval. At the same time, blood pressure improved — enough that 41% of participants in the combined 8 mg group discontinued at least one blood pressure medication during the study. Whether retatrutide reduces actual cardiovascular events is being tested in the dedicated TRIUMPH-Outcomes trial; results are years away.
Does retatrutide affect kidney function?
Renal (kidney) events were tracked as an adverse event of special interest in the Phase 2 obesity trial, and they were rare. A renal event occurred in 4 of 337 participants overall (1%), with the same low rate in the placebo group (1 of 70) as across the retatrutide dose groups (3 cases spread across the 1 mg, 4 mg, and 8 mg arms) — there was no dose-dependent pattern that would suggest the drug itself was driving kidney injury. That said, kidney safety has not been established in people who already have significant renal impairment: the trials largely excluded severe kidney disease, so safety data in that population is limited. The relevant indirect risk with any potent GLP-1-class drug is dehydration — severe nausea, vomiting, or diarrhea during dose escalation can reduce fluid intake and, in turn, stress the kidneys (acute kidney injury has been reported with other GLP-1 drugs in the setting of significant GI fluid loss). Staying hydrated through the titration phase and reporting persistent vomiting or diarrhea to a clinician is the standard precaution. Anyone with existing kidney disease should have retatrutide use overseen by a doctor who can monitor renal labs.
How much does retatrutide lower ApoB and other lipids?
A lipid sub-analysis of the Phase 2 obesity trial (NCT04881760), presented at the European Society of Cardiology Congress 2024, reported dose-dependent improvements across atherogenic lipid markers. ApoB — the particle count that many cardiologists consider a better risk marker than LDL cholesterol — fell by up to 19.6% at 24 weeks and 24.2% at 48 weeks. Over the same period, non-HDL cholesterol dropped by up to 22.2% (24 wk) and 26.9% (48 wk), triglycerides by up to 40.6%, and apoC-III by up to 38.0% at 48 weeks. The analysis also found a reduction in total and small, highly atherogenic LDL particles, and the NMR lipoprotein insulin-resistance score fell by 27.4%, 31.7%, and 32.5% at the 4 mg, 8 mg, and 12 mg doses. One marker people often ask about — lipoprotein(a), or Lp(a) — was not reported in this sub-analysis, so there is no published Phase 2 figure for it; weight-loss and GLP-1-class drugs generally have little effect on Lp(a), which is largely genetically determined. As with all of these numbers, "up to" reflects the highest dose and the largest weight loss; much of the lipid benefit tracks with the degree of weight reduction.
Sources
- Eli Lilly and Company. (2025). Lilly's retatrutide achieved significant weight loss and pain relief in adults with obesity and knee osteoarthritis. Press release.
- Jastreboff, A.M., et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. DOI: 10.1056/NEJMoa2301972
- Wilding, J.P.H., et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine. DOI: 10.1056/NEJMoa2032183
- Jastreboff, A.M., et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine. DOI: 10.1056/NEJMoa2206038
- Lincoff, A.M., et al. (2023). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). New England Journal of Medicine. DOI: 10.1056/NEJMoa2307563
- ClinicalTrials.gov: NCT04881760 (Phase 2, Obesity), NCT04867785 (Phase 2, T2D)
- Retatrutide Phase 2 lipid sub-analysis, presented at the European Society of Cardiology (ESC) Congress 2024 — ApoB, non-HDL-C, triglyceride, apoC-III, and LDL-particle changes (NCT04881760). Summary
- Sodhi, M., Rezaeianzadeh, R., Kezouh, A., Etminan, M. (2023). Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. JAMA. Full text
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Dieting & Gallstones. Full text
- Alsuwailem, O.A., Alanazi, R., Almutairi, H.M., et al. (2025). Hair Loss Associated With Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Use: A Systematic Review. Cureus 17(9):e92454. DOI: 10.7759/cureus.92454
Questions to ask your doctor
- Is a GLP-1 medication an appropriate option for my condition specifically?
- What does the evidence actually show for my condition, versus weight loss alone?
- What are the alternatives, and how do they compare for me?
- What risks or monitoring apply given my health history?
- What results would be realistic, and over what timeframe?
How we keep this honest
- What this is
- Educational information, not medical advice. It reports published research — it doesn’t recommend that you use, obtain, or supply anything.
- Regulatory status
- Retatrutide and similar peptides are investigational — not approved by the FDA or any regulator. Semaglutide and tirzepatide are prescription-only medicines, available only through a licensed prescriber.
- Our standard
- Every claim traces to a primary source. We label the strength of evidence and flag estimates as estimates — never as clinical fact.
- No commercial ties
- We don’t sell, supply, or link to suppliers of any medicine, and aren’t affiliated with any manufacturer.
Do not make decisions about your health without consulting a qualified healthcare provider. For trial enrolment, see ClinicalTrials.gov. More on how we review.
Sources
- TRIUMPH-4 press release
Eli Lilly
Grounded in primary sources
NEJM
The Lancet
JAMA
FDA
ClinicalTrials.govRelated reading
Comparison
Retatrutide vs Mounjaro vs Ozempic
How the three generations of weight loss drugs compare — single, dual, and triple agonists.
Tracker
Retatrutide Phase 3 Results 2026: TRIUMPH Trial Tracker
Living tracker of every retatrutide trial — TRIUMPH-1/2/3/4/5, TRIUMPH-Outcomes, TRANSCEND-T2D-1/2, and SYNERGY-OUTCOMES Phase 3 readouts.
Explainer
What Is Retatrutide (GLP-3)?
The world's first triple agonist weight loss drug — how it works, what the trials show, and why people call it GLP-3.
News
TRIUMPH-3 Retatrutide Results: 22.6% at 12 mg
TRIUMPH-3 reported topline results on July 23, 2026 — 22.6% weight loss at 12 mg over 80 weeks in a cardiovascular-disease population.
News
TRANSCEND-T2D-1: Retatrutide Phase 3 Diabetes Results (March 2026)
First Phase 3 retatrutide trial in type 2 diabetes — 16.8% weight loss and -2.0% A1C at 12 mg over 40 weeks. Announced March 19, 2026.
Guide
Retatrutide Dosage & Dosing Guide: Titration, Missed Doses, Taper
Phase 3 titration schedule (2→4→6→9→12 mg), missed-dose protocol, taper guidance, and dose-by-dose weight loss data.
Guide
What to Eat on Reta: Protein, Shot Day & When You Can't Eat
Operational guide: protein when appetite is broken, shot-day foods, grocery list, fiber paradox, and under-eating safety — with the research underneath.
Guide
Protein Target Calculator for Retatrutide
Daily protein target from weight and optional body fat % — lean-mass or ABW path, formula shown, appetite-broken playbook.
Safety
Does Retatrutide Cause Muscle Loss?
The first DXA body composition data for retatrutide, the glucagon muscle-sparing hypothesis, and evidence-based strategies to preserve lean mass.
Safety
Retatrutide and Alcohol: What We Know
No direct studies exist on retatrutide and alcohol, but GLP-1 receptor agonist research points to reduced intake and liver effects.
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