Zepbound Long-Term Side Effects: What 3+ Years of Data Show
Tirzepatide, the active ingredient in Zepbound, has been studied for more than three years, and the long-term picture is reassuring: no new safety concerns appeared after the first 72 weeks (Jastreboff et al., NEJM). The official warnings for this GLP-1 medication still list a few rarer risks worth knowing about, including thyroid C-cell tumors seen in rodents, pancreatitis and gallbladder problems (Zepbound prescribing information). Glapp, the GLP-1 tracker, keeps a month-by-month record of how you feel right next to your Zepbound doses, so any change over time is easy to spot.
Key numbers
| Number | What it means |
|---|---|
| 176 weeks | longest follow-up of tirzepatide for weight reduction (SURMOUNT-1), with no new safety concerns |
| 16,204 | users currently tracking long-term Zepbound side effects in Glapp |
| 0.2% vs 0.2% | pancreatitis on Zepbound vs placebo in its weight-loss trials |
Zepbound long-term safety: what the clinical evidence shows
Up to 3 years of treatment. In SURMOUNT-1, part of the group stayed on tirzepatide for 176 weeks. They kept most of their weight loss (average −12.3% at 5 mg, −18.7% at 10 mg and −19.7% at 15 mg vs −1.3% on placebo), and the side effects matched the 72-week results: mostly digestive, mostly mild to moderate, and mostly during dose increases (Jastreboff et al., NEJM 2024).
Official Zepbound warnings. These are the longer-term risks Zepbound's prescribing information asks people and prescribers to watch for:
| Warning | What the prescribing information says |
|---|---|
| Thyroid C-cell tumors (boxed warning) | Caused tumors in rats; unknown whether it does in humans. Not for people with a personal or family history of medullary thyroid cancer or MEN 2. |
| Pancreatitis | Reported in 0.2% on Zepbound and 0.2% on placebo in the weight-loss trials. |
| Gallbladder problems | Including gallstones; listed among Zepbound's official warnings. |
| Acute kidney injury | 0.5% vs 0.2% on placebo, mostly linked to dehydration from vomiting or diarrhea. |
| Severe digestive side effects | 1.7% at 5 mg, 2.5% at 10 mg and 3.1% at 15 mg vs 1% on placebo. |
| Heart rate | Average resting heart rate rose by 1–3 beats per minute. |
Source: Zepbound prescribing information, boxed warning and sections 5 and 6.
What happens after stopping. In SURMOUNT-4, everyone took tirzepatide for 36 weeks; then some switched to placebo. In a post hoc analysis, 82% of those who switched regained more than a quarter of the weight they had lost by week 88 (SURMOUNT-4, Aronne et al., JAMA 2024, and post hoc analysis).
Why some Zepbound side effects last longer
Most digestive side effects are strongest in the first weeks on each new dose and then settle. Others are tied to weight loss itself rather than the medicine: hair shedding and gallstones are both more common with fast weight loss. That's why the side effects people notice in month six are often different from the ones in week one.
Your Glapp history shows which side effects faded, which stayed and which are new.
Muscle, nutrition and other long-term things worth watching
Some long-term effects come from losing a lot of weight rather than from the medicine itself:
- Muscle (lean mass). Part of any large weight loss is muscle. In a SURMOUNT-1 body-composition substudy, roughly three-quarters of the weight lost on tirzepatide was fat and about a quarter was lean mass. Enough protein (generally 0.8–1.2 g per kg of body weight a day) helps protect muscle.
- Nutrient gaps. Months of eating less can leave you low on iron, vitamin B12, vitamin D or calcium, which can show up as tiredness or hair shedding. Ask your prescriber whether routine blood tests make sense for you.
- Gallstones. Fast weight loss raises the risk, which is one reason Zepbound's prescribing information lists gallbladder problems. Pain in the upper right of your stomach, fever or yellowing skin needs prompt care.
- Thyroid signs. Zepbound's prescribing information asks you to report a lump or swelling in your neck, hoarseness, trouble swallowing or shortness of breath.
Track your long-term Zepbound side effects with a GLP-1 tracker app
Over months, memory blurs. A GLP-1 tracker keeps the history for you: log how you feel next to your Zepbound doses, and you're in control. You'll see which side effects faded, which stuck around and what changed after each dose step, the long-term picture your prescriber needs.
Why Glapp? It's a top-rated GLP-1 tracker used by 100,000+ people, rated 4.8/5 on Trustpilot and the App Store, and 4.6/5 on Google Play. Glapp grew out of Reddit GLP-1 support groups and is built by developers who are GLP-1 users themselves, so most features come straight from community requests. Its features are grounded in peer-reviewed research and published clinical trial data, core tracking is free, and it works on iPhone, Android and web with your data synced across devices. Here's how to use it month by month, from day one.
Glapp does not provide medical advice or treat side effects. It shows your daily check-ins against your estimated medication levels so you have structured data to share with your prescriber.
Day 1: Start tracking your side effects
Use Glapp's daily check-in to record any side effects you have and rate how severe each one feels. Add your weight so later months have a baseline.
Daily entries help you see whether each side effect is getting better, getting worse or staying the same. Over months, you'll have a clear record of how you felt, without having to remember every day.
Week 1: Compare symptoms with your estimated Zepbound level
Glapp estimates your medication level throughout the day using your dose and injection time. Tirzepatide typically reaches its highest blood concentration 8–72 hours after an injection.
Seeing your symptoms alongside this estimate helps you spot when side effects appear within your shot cycle. The medication level is an estimate, not a blood test, and a matching pattern does not prove what caused your symptoms.
Month 1: See how your side effects change over time
Open the side-effects chart in the Progress tab and choose the period you want to review. Your ratings appear on a timeline, making it easier to see which side effects are fading and which are sticking around. Tirzepatide reaches a steady repeating level after about four weeks at the same dose.
Month 3: Look for patterns in your weekly reports
Glapp's weekly progress reports bring your logged data together, with dedicated sections showing your side effects and how they change.
Did a side effect return after a dose step? Does anything coincide with changes in hunger or food noise? Reviewing months of entries can help you spot patterns that are easy to miss day by day, and give you specific questions to discuss with your doctor.
Month 6 and beyond: Bring a clear record to your doctor
Review the bigger picture: which side effects have faded, which are new, and has anything come back after fading? New symptoms that don't fit your usual pattern are the ones most worth raising.
Create a doctor's report in Glapp before each review appointment and choose the information to include. Your doctor can review your symptom history alongside your doses and progress, giving you a more focused conversation about your long-term treatment.
Start tracking your Zepbound journey in Glapp
Long-term side effects at maintenance doses: 5, 10 and 15 mg
Zepbound's maintenance doses are 5, 10 and 15 mg once weekly, reached in 2.5 mg steps at least four weeks apart. In the trials, severe digestive side effects rose with dose (1.7% at 5 mg, 2.5% at 10 mg, 3.1% at 15 mg), and in the 176-week follow-up the higher doses kept off more weight.
Your weekly reports show how each dose has felt for you over time.
See every dose in the Zepbound dosage chart.
What to bring to your prescriber
A month-by-month log shows your prescriber the long-term picture:
| Month | Dose | Side effects logged | Most frequent | Trend | Weight change |
|---|---|---|---|---|---|
| Example 1 | 2.5 mg | Nausea, fatigue | Nausea (9 days) | – | −2.1% |
| Example 3 | 7.5 mg | Nausea, constipation | Constipation (8 days) | Nausea easing | −7.4% |
| Example 6 | 10 mg | Hair thinning / loss | Hair thinning / loss (12 days) | New | −13.0% |
Questions you could ask. They're conversation starters, not recommendations; your prescriber decides what, if anything, to change.
- "Which of my side effects would you want me to report straight away, and which can wait for our next visit?"
- "Do I need any check-ups while I'm on Zepbound long term?"
- "What should I expect if I stop or lower my dose?"
Frequently asked questions
Is Zepbound safe to take long term?
Tirzepatide has been studied for weight reduction for up to 176 weeks, with no new safety concerns over that time compared with the first 72 weeks. Zepbound's prescribing information lists warnings to watch for, and your prescriber decides whether long-term treatment suits you.
What are the long-term side effects of Zepbound?
The most common ones remain digestive: nausea, diarrhea, constipation and indigestion, usually strongest during dose increases. The prescribing information for this GLP-1 medication also warns about thyroid C-cell tumors (seen in rodents), pancreatitis, gallbladder problems and kidney injury from dehydration.
What happens when you stop Zepbound?
In SURMOUNT-4, 82% of people who switched from tirzepatide to placebo regained more than a quarter of the weight they had lost within a year.
Does Zepbound cause thyroid cancer?
Tirzepatide caused thyroid C-cell tumors in rats. Zepbound's prescribing information says it's unknown whether it does in humans, and Zepbound isn't for people with a personal or family history of medullary thyroid cancer or MEN 2.
About the data
Ratings are self-reported and medication levels are estimated from dose and timing, not measured. This page is for information only and is not medical advice; talk to your prescriber about any side effect.
About the author
We're GLP-1 patients and health tech professionals, building Glapp in collaboration with doctors. About us
Sources
- Eli Lilly. Zepbound (tirzepatide) prescribing information: boxed warning, warnings and precautions (section 5), adverse reactions (section 6.1).
- Jastreboff AM et al. Tirzepatide for obesity treatment and diabetes prevention. NEJM, 2024 (SURMOUNT-1, 176 weeks).
- Aronne LJ et al. Continued treatment with tirzepatide for maintenance of weight reduction (SURMOUNT-4). JAMA, 2024; and post hoc analysis of weight regain.