# Long-Term Risks of Zepbound (Tirzepatide): Clinical Guide **Prepared by:** Pedro Cheung MD **Last Updated:** May 2026 **Evidence Base:** SURMOUNT clinical trial program, FDA prescribing labels (2024–2026), peer-reviewed meta-analyses and RCTs (2023–2026), real-world FAERS pharmacovigilance data --- ## Background: What Is Zepbound? Zepbound (tirzepatide) is a **dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptor agonist** manufactured by Eli Lilly. It is structurally distinct from semaglutide (Ozempic/Wegovy): it activates _two_ incretin hormone receptors simultaneously, which contributes to its superior weight loss efficacy compared to GLP-1-only agents.[^9] **FDA-Approved Indications (as of 2024–2026):** - Chronic weight management (adults with BMI ≥30, or ≥27 with a weight-related comorbidity) — approved May 2023 - Moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity — approved December 2024[^FDA-OSA] **Key Dosing:** Subcutaneous injection once weekly. Titration begins at 2.5 mg, escalating in 2.5 mg increments every 4 weeks, to maintenance doses of 5 mg, 10 mg, or 15 mg. Maximum recommended dose: **15 mg once weekly.**[^USPI] --- ## 1. GASTROINTESTINAL COMPLICATIONS (Most Common) ### Incidence GI adverse events are the most common side effects of Zepbound, occurring in **56% of patients** across all dose groups (5 mg/10 mg/15 mg), compared with 30% in the placebo group.[^USPI] ### Specific Reactions (From FDA Label — Study 1 & 2 Pool)[^USPI] |Adverse Reaction|Placebo|Zepbound 5 mg|Zepbound 10 mg|Zepbound 15 mg| |---|---|---|---|---| |**Nausea**|8%|25%|29%|28%| |**Diarrhea**|8%|19%|21%|23%| |**Vomiting**|2%|8%|11%|13%| |**Constipation**|5%|17%|14%|11%| |**Abdominal Pain**|5%|9%|9%|10%| |**Dyspepsia**|4%|9%|9%|10%| |**GERD**|2%|4%|4%|5%| |**Eructation (burping)**|1%|4%|5%|5%| ### Key Points **Dose escalation is the peak risk period.** The majority of nausea, vomiting, and diarrhea events occurred during dose escalation and decreased over time.[^USPI] Importantly, GI side effects account for the **majority of early discontinuations** (4.8–6.7% across dose groups vs. 3.4% with placebo permanently discontinuing due to adverse reactions).[^USPI] **GI events do NOT drive weight loss.** Across the SURMOUNT-1 through -4 trials, weight reduction with tirzepatide was **similar regardless of whether patients reported GI adverse events**, with mediation analyses showing GI events account for only up to 3.1% of total weight reduction.[^8][^10] **Severe GI reactions are uncommon but possible.** Severe GI adverse reactions were reported in 1.7–3.1% of Zepbound-treated patients vs. 1% with placebo.[^USPI] Postmarketing reports include **ileus, intestinal obstruction, severe constipation, and fecal impaction.**[^USPI] **Not recommended in severe gastroparesis.** The 2026 updated prescribing label explicitly states: "Zepbound is not recommended in patients with severe gastroparesis."[^USPI] ### Clinical Recommendation Slow titration, small frequent meals, avoidance of high-fat or spicy foods during escalation, and antiemetics as needed. Warn patients that most GI symptoms peak in the first 12–20 weeks and resolve with continued therapy. --- ## 2. MUSCLE MASS LOSS (Lean Body Mass) — Important Emerging Concern ### Evidence This is a **unique and important risk** with tirzepatide (and all incretin-based therapies) that does not appear in the semaglutide handout — but deserves specific attention given tirzepatide's superior weight loss magnitude. **SURMOUNT-1 Body Composition Substudy (DXA-measured, n=160):** Of total weight lost, approximately **75% was fat mass and 25% was lean mass** with tirzepatide at 72 weeks. The mean percent change was −33.9% fat mass and **−10.9% lean mass** compared to −8.2% and −2.6% with placebo.[^5-muscle] **Clinical context:** A 10%+ loss of muscle mass over 68–72 weeks is comparable to approximately **10–20 years of age-related muscle loss (sarcopenia).**[^Mechanick] However, MRI-based studies suggest the muscle volume changes may be broadly **adaptive** (proportional to overall weight loss) rather than purely pathological, and tirzepatide is associated with significant reductions in **muscle fat infiltration**, which may improve muscle quality.[^Sattar] **Lean mass distribution:** Of weight lost with tirzepatide, approximately **25% is from lean mass**, compared to approximately 45% with semaglutide — suggesting tirzepatide may have a **relatively more favorable fat-to-lean ratio.**[^Ryan] ### High-Risk Groups Older adults (≥65 years), patients with pre-existing sarcopenia or frailty, and those with low protein intake are at greatest risk for clinically meaningful muscle loss.[^Chen][^Moscucci] ### Clinical Recommendations - Recommend **resistance exercise training** throughout treatment — studies show supervised programs >10 weeks can produce ~3 kg lean mass gain and ~25% strength improvement.[^Locatelli] - Ensure adequate **protein intake** (generally ≥1.2–1.6 g/kg/day); consider nutritional supplementation. - Discuss muscle preservation explicitly with patients before initiating therapy, particularly older adults. - Emerging evidence suggests combining a **low-energy ketogenic diet** with tirzepatide may better preserve fat-free mass, muscle strength, and resting metabolic rate compared to standard low-calorie diet.[^Schiavo] --- ## 3. THYROID CANCER (Medullary) — Boxed Warning ### FDA Black Box Warning[^USPI] > _"In rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors. It is unknown whether Zepbound causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans."_ **Contraindicated in patients with:** - Personal or family history of medullary thyroid carcinoma (MTC) - Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) ### Real-World Incidence In the tirzepatide clinical development program, **no treatment-emergent adverse events of thyroid malignancies were reported**, and calcitonin levels did not change in tirzepatide-treated groups.[^FDA-OtherR] A 15-year MTC registry-based postmarketing requirement has been mandated by the FDA to systematically monitor MTC incidence in the U.S. in relation to tirzepatide use.[^FDA-OtherR] ### Clinical Recommendation - Routine monitoring of serum calcitonin or thyroid ultrasound **is not recommended as standard practice** (uncertain value, risk of unnecessary procedures). - Counsel patients to report neck masses, hoarseness, dysphagia, or dyspnea promptly. - If calcitonin is measured and elevated >50 ng/L, further evaluation is warranted.[^USPI] --- ## 4. GASTROINTESTINAL SERIOUS EVENTS: PANCREATITIS & ILEUS ### Acute Pancreatitis **Incidence from Zepbound weight reduction trials (Studies 1 & 2):** Confirmed pancreatitis was reported in **0.2% of Zepbound-treated patients** vs. 0.2% of placebo-treated patients (0.14 vs. 0.15 patients per 100 person-years of exposure).[^USPI] In tirzepatide diabetes trials, a slightly higher exposure-adjusted incidence was observed: 0.23 per 100 person-years (tirzepatide) vs. 0.11 (comparator).[^USPI] Postmarketing reports include **fatal and non-fatal hemorrhagic and necrotizing pancreatitis.**[^USPI] **Clinical Action:** Discontinue Zepbound if pancreatitis is suspected. Evaluate for acute pancreatitis (severe epigastric pain radiating to back, elevated lipase/amylase) in patients on GLP-1/GIP agonists presenting with acute abdominal pain. **Amylase/Lipase Elevations:** Zepbound causes mean increases of 20–25% in pancreatic amylase and 28–35% in lipase without confirmed pancreatitis. The clinical significance of asymptomatic enzyme elevations is unknown.[^USPI] ### Bowel Obstruction / Ileus Postmarketing reports include **ileus and intestinal obstruction** with tirzepatide.[^USPI] Gastroparesis-related retained gastric contents are a documented concern, particularly for patients undergoing **endoscopy or general anesthesia** (see Section 9 — Aspiration Risk). --- ## 5. CHOLELITHIASIS (Gallstones) & BILIARY DISEASE ### Incidence (Studies 1 & 2)[^USPI] |Event|Zepbound|Placebo| |---|---|---| |Cholelithiasis (gallstones)|1.1%|1.0%| |Cholecystitis|0.7%|0.2%| |Cholecystectomy|0.2%|0%| Cholecystitis was **3.5× more frequent** with Zepbound than placebo. Acute gallbladder events were associated with weight reduction. ### Mechanism Delayed gastric emptying and altered bile acid metabolism increase cholesterol saturation and promote gallstone formation. Rapid weight loss itself is an independent risk factor for cholelithiasis. ### Clinical Recommendation Evaluate patients with right upper quadrant pain, nausea, or fever with ultrasound. Elective cholecystectomy may be needed for symptomatic cholelithiasis. Consider baseline ultrasound in high-risk patients (prior biliary history, obesity-related rapid weight loss). --- ## 6. ACUTE KIDNEY INJURY — Primarily Dehydration-Mediated ### Direct Drug Effect Renal pharmacokinetics are **not affected by renal impairment** — no dose adjustment is needed even in end-stage renal disease.[^USPI] In the pooled weight reduction trials, acute kidney injury occurred in **0.5% of Zepbound-treated patients vs. 0.2% of placebo patients.**[^USPI] ### Indirect Risk Postmarketing reports include **acute renal failure requiring hemodialysis**, primarily in patients who experienced severe GI adverse events leading to dehydration.[^USPI] High-risk groups: elderly patients, those with baseline CKD, concurrent NSAID, ACE inhibitor, or diuretic use. ### Renal Benefit Signal Real-world data from a large cohort (n=14,834 tirzepatide-treated patients with T2DM) showed tirzepatide was associated with lower hazard of **kidney events (AHR 0.52), acute kidney injury (AHR 0.78), and major adverse kidney events (AHR 0.54)** compared with GLP-1 receptor agonists.[^Chuang] ### Clinical Recommendation Monitor renal function in patients with reactions that could lead to volume depletion, especially during dose initiation and escalation. Educate patients on hydration. --- ## 7. CARDIOVASCULAR EFFECTS ### Heart Rate Zepbound results in a mean increase in heart rate of **1–3 beats per minute** vs. no increase in placebo.[^USPI] No increase in arrhythmia or QTc prolongation has been identified.[^FDA-ClinPharm] ### Hypotension Hypotension occurred in **1.6% of Zepbound-treated patients vs. 0.1% with placebo**. Risk is higher in patients on concomitant antihypertensive therapy (2.2%) and with GI-related dehydration.[^USPI] ### Cardiovascular Outcomes — Benefit Signal A meta-analysis of 20 RCTs (n=15,905 participants) found **no significant association between tirzepatide and adverse cardiovascular events** (RR 0.83, 95% CI 0.63–1.08).[^Springer] Real-world data showed tirzepatide associated with **lower hazard of major adverse cardiovascular events (AHR 0.80)** and **all-cause mortality (AHR 0.58)** compared to GLP-1 receptor agonists in patients with T2DM.[^Chuang] The dedicated cardiovascular outcomes trial (**SURMOUNT-MMO**) for tirzepatide in patients with obesity without diabetes is ongoing and anticipated to report in 2027. Results comparable to the semaglutide SELECT trial would be expected but are not yet confirmed. **Blood Pressure Benefits (Studies 1 & 2):** Tirzepatide reduced systolic blood pressure by 5.1–6.3 mmHg and diastolic by 3.7–4.2 mmHg vs. placebo.[^USPI] --- ## 8. HYPOGLYCEMIA (With Concurrent Insulin/Sulfonylureas) ### Risk Profile[^USPI] In Study 2 (patients with T2DM, BMI ≥27): - Hypoglycemia (plasma glucose <54 mg/dL): **4.2% Zepbound vs. 1.3% placebo** - With concomitant **sulfonylurea**: **10.3%** hypoglycemia rate - Without sulfonylurea: **2.1%** In non-diabetic patients, severe hypoglycemia is rare but has been reported. ### Mitigation Reduce insulin or sulfonylurea dose when initiating Zepbound. Educate patients on hypoglycemia recognition and management (glucose tablets, glucagon kit if warranted). --- ## 9. PULMONARY ASPIRATION DURING SURGERY/PROCEDURES ### Important 2026 Update This is a **new and clinically important warning** added to the Zepbound prescribing label. Tirzepatide delays gastric emptying. Postmarketing reports have identified cases of **pulmonary aspiration during elective surgeries or procedures requiring general anesthesia or deep sedation**, occurring in patients who reported adherence to standard fasting recommendations but had residual gastric contents.[^USPI] ### Clinical Recommendation - **Instruct all patients to inform their surgeon, anesthesiologist, and endoscopist** that they are on Zepbound before any planned procedure. - Consider modified fasting protocols or temporary dose interruption (discuss with proceduralist and patient). - Note: The FDA states available data are currently insufficient to define optimal fasting modifications. --- ## 10. DIABETIC RETINOPATHY COMPLICATIONS — Diabetic Patients Only ### Evidence and Mechanism Rapid glycemic improvement can temporarily worsen diabetic retinopathy ("early worsening" or pseudoregression phenomenon). The Zepbound prescribing label states tirzepatide **has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema.**[^USPI] In pooled tirzepatide diabetes trials, diabetic retinopathy complications were identified as a potential risk.[^FDA-NDA] ### Clinical Recommendation - Baseline dilated eye exam before initiation in all patients with T2DM. - Monitor diabetic patients closely for any vision changes. - Refer to ophthalmology if pre-existing diabetic retinopathy is present — particularly proliferative disease or diabetic macular edema. --- ## 11. HYPERSENSITIVITY REACTIONS ### Incidence (Studies 1 & 2)[^USPI] - Immediate hypersensitivity reactions (within 24 hours): **2.1% Zepbound vs. 0.4% placebo** - Non-immediate hypersensitivity: **3.5% vs. 2.7%** - Patients who developed anti-tirzepatide antibodies (64.5% of treated patients) had higher hypersensitivity rates: **6.2% vs. 3%** Postmarketing reports include **anaphylaxis and angioedema.**[^USPI] ### Clinical Recommendation Zepbound is **contraindicated in patients with known serious hypersensitivity to tirzepatide**. Advise patients to seek emergency care immediately for signs of anaphylaxis (hives, swelling, difficulty breathing). Caution in patients with prior GLP-1 agonist–associated angioedema or anaphylaxis. --- ## 12. HAIR LOSS (Alopecia) ### Incidence[^USPI] Hair loss was reported more frequently with Zepbound: - Female patients: **7.1% Zepbound vs. 1.3% placebo** - Male patients: **0.5% vs. 0%** Hair loss was associated with weight reduction (likely telogen effluvium triggered by caloric restriction and rapid weight change), not a direct drug toxicity. No patients discontinued treatment due to hair loss. ### Clinical Recommendation Counsel patients, particularly women, that hair shedding typically begins 2–4 months into treatment and is self-limiting. Protein-adequate nutrition reduces severity. No treatment discontinuation typically required. --- ## 13. INJECTION SITE REACTIONS ### Incidence[^USPI] Injection site reactions (bruising, erythema, pruritus, pain, rash): **6–8% of Zepbound patients vs. 2% placebo**. More common in those who develop anti-tirzepatide antibodies (**11.3% vs. 1%**). Rotate injection sites (abdomen, thigh, or upper arm by another person) with each dose to minimize local reactions. --- ## 14. DRUG INTERACTIONS — ORAL CONTRACEPTIVES ### Important Clinical Pearl Tirzepatide delays gastric emptying, which can **reduce the absorption of oral medications**, particularly during the first dose and dose escalations.[^USPI] **Oral contraceptives:** Following initiation of Zepbound, mean Cmax of ethinyl estradiol was reduced by 59% and AUC by 20%. Tirzepatide's effect on gastric emptying diminishes over time. **Clinical Recommendation:** Advise patients using **oral hormonal contraceptives** to: - Switch to a non-oral method (patch, ring, injection, IUD), **or** - Add a barrier method of contraception for **4 weeks after initiation** and for **4 weeks after each dose escalation**.[^USPI] This is a unique and important clinical difference from semaglutide that patients must be counseled on. --- ## 15. MENTAL HEALTH & SUICIDALITY — Updated 2026 ### Current Status As of February 2026, the **suicidal behavior and ideation warning was removed** from the Zepbound prescribing label — reflecting the accumulation of evidence that did not confirm a causal link.[^USPI-update] ### Evidence Real-world studies show **no clear increase** in risks of depression or self-harm with GLP-1/GIP receptor agonists.[^Thomsen] Ongoing pharmacovigilance for mood and behavioral changes is still warranted, particularly during periods of rapid weight loss. --- ## 16. WEIGHT REGAIN AFTER DISCONTINUATION ### Evidence The SURMOUNT-4 randomized withdrawal trial demonstrates clearly that **stopping tirzepatide leads to substantial weight regain.** At 88 weeks, patients who continued tirzepatide had a cumulative weight loss of 25.3% vs. 9.9% in those switched to placebo; patients who stopped tirzepatide regained approximately 14% body weight over 52 weeks.[^Aronne] ### Patient Expectation This is a **chronic, long-term medication**. Weight loss is not permanent after stopping. Counsel patients on the relapsing nature of obesity and the role of ongoing maintenance therapy. Insurance coverage and access barriers remain significant real-world challenges. --- ## 17. SPECIAL POPULATIONS & CONTRAINDICATIONS ### Pregnancy **Discontinue Zepbound when pregnancy is recognized.** Animal studies show fetal growth reductions and malformations at clinically relevant exposures. Weight loss offers no benefit during pregnancy.[^USPI] A pregnancy exposure registry is maintained by Eli Lilly (1-800-LillyRx). ### Pediatric Use **Safety and efficacy have not been established in pediatric patients.**[^USPI] ### Renal/Hepatic Impairment **No dose adjustment required** for renal or hepatic impairment. Tirzepatide pharmacokinetics are not affected by these conditions.[^USPI] ### Dosing Errors — Real-World Alert A FAERS analysis of 65,974 adverse event reports (2022–Q1 2025) identified **incorrect dose administration as the top adverse event**, with reports increasing 8-fold from 2022 to 2024. Risk signals for dosing errors were consistently high (ROR 22–27).[^FAERS] Patient and caregiver education on injection technique and dose selection is essential, particularly with new multi-dose vial and KwikPen presentations. --- ## Safety Monitoring Checklist for Long-Term Use |**Domain**|**Baseline Assessment**|**During Therapy**|**Monitoring Frequency**| |---|---|---|---| |**GI Tolerance**|GI history; screen for gastroparesis|Monthly during titration; assess for severe symptoms|Each visit; ED referral if severe dehydration| |**Muscle Mass / Frailty**|Baseline body composition (BMI, grip strength for elderly)|Counsel on resistance exercise + protein intake|Consider DEXA in high-risk (elderly, low baseline muscle)| |**Thyroid**|TSH; counsel on MTC symptoms; assess MEN2/MTC history|Report neck mass, hoarseness, dysphagia|If symptomatic; calcitonin if nodule found| |**Vision (Diabetic Patients)**|Dilated eye exam if T2DM|Ask about vision changes|Annually or if symptomatic| |**Gallbladder**|RUQ ultrasound if high risk|Ask about RUQ pain/nausea|As needed| |**Kidney Function**|eGFR, creatinine|Monitor if GI dehydration occurs|Annually; urgently if severe GI events| |**Cardiovascular**|BP, HR, EKG if indicated|BP/HR each visit|Per standard care| |**Hypoglycemia**|Glucose-lowering medication reconciliation|Reduce insulin/sulfonylurea dose if added|Ongoing with each dose adjustment| |**Oral Contraceptives**|Contraceptive method|Switch to non-oral or add barrier method|4 weeks post-initiation; 4 weeks post-escalation| |**Surgical Procedures**|Counsel at initiation|Instruct patient to always inform surgical team|Prior to any elective procedure| |**Mental Health**|Screen for depression/anxiety|Ask about mood, behavior|Each visit| |**Hair Loss**|Counsel female patients proactively|Reassure; optimize protein intake|As needed| |**Injection Technique**|Train at initiation|Reassess if site reactions develop|As needed| --- ## Bottom Line for Patients ✓ **Most common risks are GI** (nausea, diarrhea, vomiting) — dose-dependent, typically peak during escalation, and improve with time. ✓ **Muscle loss is real but manageable** — resistance exercise and adequate protein are essential adjuncts to protect lean body mass. ✓ **Thyroid cancer** — contraindicated in personal/family history of MTC or MEN2; routine calcitonin monitoring is not recommended for most patients. ✓ **Gallbladder disease** — cholecystitis 3.5× more common than placebo; evaluate promptly for biliary symptoms. ✓ **Surgery requires advance notice** — always tell your surgical and anesthesia team you are on Zepbound to avoid aspiration complications. ✓ **Oral contraceptives** — switch method or add barrier for 4 weeks after starting or dose escalation; unique to tirzepatide vs. prior agents. ✓ **Discontinuation causes weight regain** — this is a long-term treatment; stopping results in substantial weight return. ✓ **Cardiovascular and metabolic benefits** — real-world data strongly suggest cardiovascular, kidney, and mortality benefits; dedicated CVOT results expected ~2027. --- ## Sources and References [^9]: Aronne LJ, et al. 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[https://consensus.app/papers/details/9e4a853234ec5e2d931b6ec502b34966/](https://consensus.app/papers/details/9e4a853234ec5e2d931b6ec502b34966/) [^Schiavo]: Schiavo L, et al. (2025). Preliminary Evidence Suggests That a 12-Week Treatment with Tirzepatide Plus Low-Energy Ketogenic Therapy Is More Effective than Its Combination with a Low-Calorie Diet in Preserving Fat-Free Mass. _Nutrients_, 10 citations. [https://consensus.app/papers/details/0e4927a6d0f955edbcb9d520b945d612/](https://consensus.app/papers/details/0e4927a6d0f955edbcb9d520b945d612/) [^Chuang]: Chuang MH, et al. (2024). Clinical Outcomes of Tirzepatide or GLP-1 Receptor Agonists in Individuals With Type 2 Diabetes. _JAMA Network Open_, 60 citations. [https://consensus.app/papers/details/daddfeb2d4eb526185905f77ca7d98d9/](https://consensus.app/papers/details/daddfeb2d4eb526185905f77ca7d98d9/) [^Springer]: [Tirzepatide cardiovascular and renal adverse events meta-analysis.](https://link.springer.com/article/10.1186/s13098-025-02064-1) _Diabetology & Metabolic Syndrome_ (2025). 20 RCTs, n=15,905 participants. [^Thomsen]: Thomsen R, et al. (2025). Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. _Diabetes, Obesity & Metabolism_, 55 citations. [https://consensus.app/papers/details/49819fd7115354c1b29028153d1ba4ef/](https://consensus.app/papers/details/49819fd7115354c1b29028153d1ba4ef/) [^Jalleh]: Jalleh R, et al. (2026). The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications. _Journal of Clinical Investigation_. [https://consensus.app/papers/details/61b62bd5c0ff57659345fb44a9cac8a8/](https://consensus.app/papers/details/61b62bd5c0ff57659345fb44a9cac8a8/) [^Kunutsor]: Kunutsor SK, et al. (2025). Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists: A State-of-the-Art Narrative Review. _Drugs_. [https://consensus.app/papers/details/99c613e10ae55971a67c940e62002b6c/](https://consensus.app/papers/details/99c613e10ae55971a67c940e62002b6c/) [^Frontiers]: [Efficacy and safety of tirzepatide for weight loss in patients with obesity or type 2 diabetes: a systematic review and meta-analysis.](https://www.frontiersin.org/articles/10.3389/fendo.2025.1593134) _Frontiers in Endocrinology_ (2025). [^FAERS]: [Real-World Safety Concerns of Tirzepatide: A Retrospective Analysis of FAERS Data (2022–2025).](https://pmc.ncbi.nlm.nih.gov/articles/PMC12469573/) _PMC_ (2025). n=65,974 reports. [^USPI-update]: Zepbound Prescribing Information, Revised 02/2026: Suicidal Behavior and Ideation warning removed. [https://pi.lilly.com/us/zepbound-uspi.pdf](https://pi.lilly.com/us/zepbound-uspi.pdf) --- ## Document Information - **Created:** May 2026 - **Format:** Markdown with complete citation footnotes - **Intended Audience:** Healthcare providers, patients, clinical educators - **Evidence Quality:** Phase 3 RCTs (SURMOUNT-1–4, SURMOUNT-OSA), FDA prescribing labels (April 2026), peer-reviewed meta-analyses and systematic reviews (2023–2026), real-world cohort studies and FAERS pharmacovigilance data - **Disclaimer:** This document is for informational purposes and should not replace clinical judgment or direct patient consultation.