Zepbound® and kidney stones

The only stones in the label are gallstones

A search of the three sets of tirzepatide product information for nephrolithiasis, urolithiasis, calculus and kidney stone found no entry ^[1][3][4]. Stones do appear, but in the gallbladder: in SURMOUNT-1 and SURMOUNT-2, gallstones were reported in 1.1% on Zepbound® and 1% on placebo, and the label links acute gallbladder events to weight reduction ^[1]. The kidney entries are about injury from fluid loss.

What tirzepatide trials show

Kidney stones are uncommon events, so single trials cannot answer the question; pooled analyses can say a little more. A 2025 meta-analysis of 15 randomised trials covering 14,471 people, with and without diabetes, found that tirzepatide, pooled or dose by dose, did not raise the risk of kidney stones, acute kidney injury, urinary tract infection or other kidney events compared with placebo, insulin or GLP-1 medicines ^[5]. A second meta-analysis of 20 trials and 15,905 participants found no significant difference in kidney adverse events, which included stones, and the result held when trials were split into diabetes and obesity groups ^[6].

Both have limits. Follow-up ran mostly from six months to about a year and a half, outcome definitions differed between trials, and the authors of the second analysis say longer-term safety in high-risk groups cannot be settled yet ^[5][6].

Uric acid, oxalate and weight loss

Two findings point in a reassuring direction. In a post hoc analysis of SURMOUNT-1, the trial behind Zepbound®’s weight indication, serum uric acid fell by 0.69 to 0.95 mg/dL across the three doses after 72 weeks, against 0.18 mg/dL on placebo, and mediation analysis attributed about 73% of the drop to weight loss ^[7]. MedlinePlus notes that uric acid stones can occur with gout ^[10]. The analysis measured blood levels, not stones.

A retrospective study followed 44 people with obesity and a history of kidney stones who lost weight on GLP-1-based medicines, a group that included dual GLP-1/GIP agonists, the class tirzepatide belongs to, for a median of about a year. Their 24-hour urine oxalate fell and their urine saturation for the main stone types did not change, which the authors contrast with other weight-loss approaches ^[8]. A 2026 systematic review notes that one of those approaches, Roux-en-Y gastric bypass, raises stone risk 2.5- to 4-fold through excess oxalate absorption, while sleeve gastrectomy does not ^[9].

Where fluids link Zepbound® and the kidneys

Three layers, from best to least supported.

• Supported by the label. Nausea, vomiting and diarrhea can dehydrate you, and dehydration can injure the kidneys; most of these stomach effects occur while the dose is being raised, and the label asks for kidney function checks in people with fluid-losing reactions, especially at the start and after dose increases ^[1].
• Plausible but not measured. Eating much less also removes the water contained in food, and nausea can make drinking harder. No Zepbound® study has measured whether this changes stone risk.
• General medical knowledge. Stones form when urine carries too much of the substances that crystallise, such as calcium, oxalate and phosphorus, and too little fluid concentrates them ^[10][12].

Other reasons stones form

MedlinePlus describes several stone types. Calcium stones, usually combined with oxalate, are the most common; oxalate is found in foods such as spinach and in vitamin C supplements, and diseases of the small intestine raise the risk ^[10]. Uric acid stones are linked with gout, struvite stones with repeated urinary infections, and cystine stones with an inherited condition; some medicines can also form stones, and some types run in families ^[10].

NIDDK adds that being overweight increases the risk ^[11]. For many people starting Zepbound®, that means their starting risk was already higher than average, which matters when interpreting a stone that appears during treatment.

Telling stone pain from other Zepbound® warnings

Zepbound®’s Medication Guide describes two kinds of abdominal pain that need urgent attention, and both can be confused with a stone ^[2].

• Kidney stone: sharp pain in the back, side, lower abdomen or groin that may come in waves, with pink, red or brown urine, pain when passing urine, cloudy or bad-smelling urine, and sometimes nausea, vomiting, fever or chills ^[12].
• Pancreatitis: intense stomach pain that persists, at times reaching the back, with or without vomiting; the Medication Guide says to stop Zepbound® and call your provider ^[2].
• Gallbladder: pain in the upper stomach, fever, yellow skin or eyes, or clay-coloured stools; the Medication Guide asks you to contact your provider right away ^[2].

What may help

NIDDK calls drinking enough liquid, mainly water, the most important step for preventing kidney stones, and to check with a health professional how much you should drink, since the usual advice does not apply to people with kidney failure ^[11]. It reports that the DASH eating pattern can lower stone risk, and that people who have already had a stone may be advised to adjust sodium, animal protein, calcium or oxalate depending on the stone type, while still eating enough protein ^[11].

That protein point is relevant on Zepbound®, where higher-protein eating is often discussed. NIDDK notes that animal protein may raise stone risk and suggests talking with a professional about how much total protein you need and how much should come from plants ^[11]. The Medication Guide’s request is simpler: drink fluids to help prevent dehydration ^[2].

Zepbound® and Mounjaro® are registered trademarks of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company.

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