Kidney Stones on a GLP-1 Microdose: Risk, Hydration, and What the Cohort Studies Show
Extra weight raises the odds of kidney stones, and GLP-1 medicines take weight off. So why did one of the largest GLP-1 safety studies find more stones, not fewer? The answer sits in urine chemistry, comparison groups and how much people drink.
2.09
RELATIVE STONE RISK FOR YOUNGER WOMEN WITH A BMI OF 30 OR MORE
40 → 32
URINE OXALATE (MG/D) BEFORE AND DURING GLP-1 WEIGHT LOSS IN STONE FORMERS
21.3
STONES PER 1000 PERSON-YEARS AFTER STARTING A GLP-1 IN TYPE 2 DIABETES
Kidney stones on a GLP-1 microdose are a fair worry. Stones are common: the NIDDK puts lifetime odds at about 11 percent for men and 6 percent for women in the United States. Anyone who has passed one remembers it, and anyone starting a new medicine wants to know whether it nudges those odds up or down.
The research pulls in two directions. Weight loss should help, because obesity is a known stone risk. Yet GLP-1 medicines also cut food and fluid intake and can cause vomiting or diarrhea, and dehydration concentrates urine. This article lays out what the urine studies, the big health-record cohorts and a 2026 urology review found. All of it used prescribed doses. None of it tested a sub-label microdose.
Key takeaways
- •In three Harvard cohorts with 4827 stone cases, a BMI of 30 or more carried a relative risk of kidney stones of 1.33 in men, 1.90 in older women and 2.09 in younger women.
- •In 44 obese stone formers on GLP-based therapy, urine oxalate fell from 40 to 32 mg per day, and no urine change that favours stones was seen.
- •A Veterans Affairs study of 215,970 GLP-1 starters with diabetes linked GLP-1 use with a higher risk of kidney stones than usual care.
- •In type 2 diabetes, kidney stones were less frequent after starting an SGLT2 inhibitor than a GLP-1 medicine: 14.9 versus 21.3 events per 1000 person-years.
- •The NIDDK calls drinking enough liquid, mainly water, the most important step to prevent stones. No study has measured stone risk at microdoses.
Why does body weight affect kidney stone risk?
Heavier bodies tend to excrete more of the substances that form stones, and large cohorts show the risk climbing with weight. Taylor, Stampfer and Curhan (JAMA, 2005) followed 45,988 men in the Health Professionals Follow-up Study and 93,758 older and 101,877 younger women in the two Nurses' Health Studies. Across 46 years of combined follow-up, they recorded 4827 new symptomatic stones.
Kidney stone risk with a BMI of 30 or more (relative risk vs BMI 21 to 22.9)
Taylor EN et al., JAMA 2005. Adjusted for age, diet, fluid intake and thiazide use. A value of 1 means no difference.
Weight gain over adult life told the same story. Gaining more than 35 lb (15.9 kg) since early adulthood was linked with a relative risk of 1.39 in men, 1.70 in older women and 1.82 in younger women, compared with people whose weight stayed stable. The authors concluded that the extra risk may be greater in women than in men.
Kidney stone risk after gaining more than 35 lb since early adulthood (relative risk vs stable weight)
Taylor EN et al., JAMA 2005. Men measured from age 21, women from age 18.
Those numbers explain the hope behind GLP-1 medicines. If weight drives stone risk, losing weight ought to lower it. That logic is reasonable, but a cohort study of weight cannot show that losing weight with a drug reverses the risk. For that, researchers had to look at the urine itself.
What happens to urine chemistry during GLP-1 weight loss?
In people who already form stones, GLP-1 weight loss did not shift urine toward stone formation, and oxalate went down. Feghali, Li and Maalouf (Kidney360, 2024) reviewed 44 obese stone formers at a UT Southwestern weight clinic who completed at least two 24-hour urine collections, one before and one during GLP-1 or dual GLP-1/GIP therapy. Over a median 1.1 years, they lost an average of 6.6 kg.
24-hour urine excretion before and during GLP-based therapy
Feghali K et al., Kidney360 2024. 44 stone formers with obesity. All three decreases were statistically significant. Units differ by marker.
- Before
- During therapy
Oxalate matters because it is one half of calcium oxalate stones. Calcium, citrate, uric acid, pH and total urine volume did not change significantly, and neither did the saturation measures that estimate how readily crystals form. The authors wrote that GLP-based weight loss was not linked with stone-promoting urine changes, "unlike what happens with other weight loss modalities."
A second urine study was less encouraging. Schaub and colleagues (Kidney360, 2025) used Medicare records of stone patients with diabetes and compared 349 GLP-1 users with 349 matched controls. They found no significant differences in any urine parameter, and no changes in a longitudinal group of 154 GLP-1 users either. Their summary was blunt: GLP-1 medicines were not associated with changes that would reduce stone risk. Put the two studies together and the fair reading is neutral. GLP-1 therapy does not seem to make urine worse, and it has not been shown to make it much better.
Do GLP-1 medicines raise the risk of kidney stones?
One very large study found a higher risk, though it cannot prove the drug caused it. Xie, Choi and Al-Aly (Nature Medicine, 2025) mapped 175 health outcomes in Veterans Affairs records, comparing 215,970 people with diabetes who started a GLP-1 medicine against 1,203,097 who stayed on other glucose-lowering drugs. Nephrolithiasis, the medical term for kidney stones, was on the list of outcomes that rose with GLP-1 use, alongside gastrointestinal disorders, low blood pressure and fainting.
A broad screen like this is built to flag signals, not to explain them. The study population had diabetes, and the summary does not report how much people drank or whether they had stomach side effects. Dehydration is the most plausible link, because it ties the stone signal to the gastrointestinal and blood pressure signals found in the same analysis. That explanation is still a hypothesis.
The Wegovy prescribing information supports taking fluid loss seriously. It describes postmarketing reports of acute kidney injury, some needing dialysis, and notes that most occurred in people who became dehydrated from nausea, vomiting or diarrhea. Clinicians are told to monitor kidney function in those patients, especially while the dose is being started or raised. That warning is about acute kidney injury, not stones, but the shared root is the same: not enough fluid.
How do GLP-1 medicines compare with SGLT2 inhibitors for kidney stones?
In type 2 diabetes, people starting an SGLT2 inhibitor had fewer stones than people starting a GLP-1 medicine. Paik and colleagues (JAMA Internal Medicine, 2024) matched 716,406 commercially insured adults into 358,203 pairs. Over a median 192 days, stones were diagnosed at 14.9 per 1000 person-years after an SGLT2 inhibitor and 21.3 after a GLP-1 medicine, a hazard ratio of 0.69.
Kidney stone events per 1000 person-years after starting each drug class
Paik JM et al., JAMA Intern Med 2024. Propensity-matched new users with type 2 diabetes, two separate pairwise comparisons.
- SGLT2 inhibitor
- Comparator (GLP-1 RA or DPP4i)
Notice the second pair. SGLT2 inhibitors also beat DPP-4 inhibitors, 14.6 versus 19.9, and DPP-4 inhibitors do little to body weight. That pattern suggests the gap is mostly about something SGLT2 inhibitors add rather than something GLP-1 medicines take away. The Schaub urine study points to what that is: SGLT2 users made more urine and excreted more citrate (838 versus 636 mg), with better calcium phosphate saturation scores.
Mean 24-hour urine volume in stone formers (litres)
Schaub JA et al., Kidney360 2025. 124 SGLT2 inhibitor users vs 620 matched controls. GLP-1 users in the same study showed no significant change in volume.
A 2026 European Association of Urology Endourology systematic review by Pischetola and colleagues (Translational Andrology and Urology) gathered six observational studies. Against GLP-1 medicines, SGLT2 inhibitors were linked with lower incident and recurrent stones, with hazard ratios from 0.51 to 0.69. Every study was judged at moderate risk of bias, and the reviewers asked for prospective trials with stone outcomes set in advance. For readers without diabetes, these comparisons say little, because SGLT2 inhibitors are not weight-loss drugs.
Can you take a GLP-1 if you have had kidney stones before?
A history of stones is not a listed reason to avoid GLP-1 medicines, but recurrences do happen and the prescriber should know. Danau and colleagues (Journal of Clinical Medicine, 2026) followed 126 prior stone formers at a Bucharest hospital after they started semaglutide or tirzepatide. Over a median 9 months, 13 of them (10.3%) had a new symptomatic or growing stone.
Romanian cohort of prior stone formers starting a GLP-1 medicine (number of people)
Danau RA et al., J Clin Med 2026. Single centre, no untreated comparison group, median follow-up 9 months.
Nothing the team measured, including kidney function, electrolytes, drug choice and hydration-related factors, clearly separated the people who had a recurrence from those who did not. The authors were candid that the study cannot estimate how much risk the drugs added, because it lacked an untreated comparison group. Recurrence is common in stone formers whatever medicine they take.
In practice, past stone formers often benefit from a 24-hour urine test before starting, because it shows which stone type and which urine imbalance to target. Our guide to GLP-1 microdosing and kidney health covers the broader kidney picture, and the gout and uric acid article is relevant for anyone who has had uric acid stones.
How can you lower kidney stone risk on a GLP-1 microdose?
Drink enough. The NIDDK calls drinking enough liquid, mainly water, the most important thing a person can do to prevent kidney stones, and notes that many professionals recommend six to eight 8-ounce glasses a day for people without kidney failure. On a GLP-1, that takes more intent than usual, because eating less can quietly mean drinking less too, although no study has measured fluid intake on GLP-1 medicines.
Practical habits that follow from the evidence:
- •Keep water within reach and drink through the day, since appetite cues for food and drink both quieten on a GLP-1.
- •Replace fluid quickly after vomiting or diarrhea, and call the prescriber if you cannot keep fluids down. Our sick-day rules article covers this in detail.
- •If you have had calcium oxalate stones, the NIDDK lists foods to limit, including nuts, peanuts, rhubarb, spinach and wheat bran.
- •Watch sodium and animal protein, which the NIDDK names as diet factors stone formers may need to adjust. The DASH eating pattern is linked with lower stone risk.
- •Treat flank pain, blood in the urine, or fever with urinary symptoms as reasons to see a clinician promptly.
Protein targets on a GLP-1 can pull against stone advice, because high animal protein intake is one of the factors the NIDDK flags. A dietitian can balance the two. Our protein strategy guide explains why protein matters for muscle while the scale moves.
Weight loss on a GLP-1 does not appear to make urine more stone-prone, and oxalate may fall. Large cohorts still show more stones on GLP-1 medicines than on SGLT2 inhibitors, and fluid loss is the likeliest reason. Steady hydration is the one step every source agrees on.
Frequently asked questions
Do GLP-1 medicines cause kidney stones?
The evidence is mixed and comes from observational studies, so cause has not been shown. A Veterans Affairs cohort of 215,970 GLP-1 starters with diabetes found a higher risk of kidney stones than usual care, while a study of 44 stone formers found no harmful changes in urine chemistry during GLP-1 weight loss. No randomised trial has been designed around stone outcomes.
Does losing weight on a GLP-1 lower kidney stone risk?
It may, but that has not been proven. Obesity and weight gain are linked with higher stone risk in large cohorts, with a relative risk of 2.09 for younger women with a BMI of 30 or more. In 44 stone formers who lost an average of 6.6 kg on GLP-based therapy, urine oxalate fell from 40 to 32 mg per day, which points the right way.
Is semaglutide or tirzepatide worse for kidney stones?
No study has compared them head to head for stones. The Romanian cohort included 94 semaglutide users and 32 tirzepatide users but found no treatment characteristic that separated people who had a recurrence from those who did not. Both drugs carry the same practical concern, which is dehydration from nausea, vomiting or diarrhea.
Are SGLT2 inhibitors better than GLP-1 medicines for people who get stones?
In people with type 2 diabetes, observational data favour SGLT2 inhibitors. In a matched cohort of 716,406 adults, stones occurred at 14.9 per 1000 person-years after starting an SGLT2 inhibitor versus 21.3 after a GLP-1 medicine. An EAU Endourology review of six studies found the same direction, with moderate risk of bias in all of them.
How much water should I drink on a GLP-1 microdose?
The NIDDK says many health professionals recommend six to eight 8-ounce glasses of liquid a day, mainly water, unless you have kidney failure. Drinking enough is described as the most important thing you can do to prevent stones. People with heart or kidney conditions should ask their own clinician for a target.
Can dehydration on a GLP-1 hurt the kidneys?
Yes. The Wegovy prescribing information lists acute kidney injury due to volume depletion, with most reported cases in people dehydrated by nausea, vomiting or diarrhea. The label tells clinicians to monitor kidney function in people with those symptoms, especially when starting or increasing the dose.
I have had kidney stones before. Can I still use a GLP-1?
A past stone is not listed as a reason to avoid GLP-1 medicines, but it is worth telling the prescriber. In one Romanian cohort of 126 prior stone formers, 13 people (10.3%) had a recurrence within a median of 9 months, though the study had no untreated comparison group. A urologist may suggest a 24-hour urine test to guide diet and fluid targets.
Does a microdose change any of this?
No study has measured kidney stones at sub-label microdoses. Every study in this article used standard prescribed doses, mostly in people with type 2 diabetes. A lower dose may mean fewer stomach side effects and less risk of dehydration, but that has not been tested for stone outcomes.
Clinical references
- Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005. doi:10.1001/jama.293.4.455
- Feghali K, Li X, Maalouf NM. Changes in 24-Hour Urine Chemistry in Patients with Nephrolithiasis during Weight Loss with Glucagon-Like Peptide 1-Based Therapies. Kidney360. 2024. doi:10.34067/KID.0000000580
- Schaub JA, Oerline MK, Crivelli JJ, et al. The Effect of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists on 24-Hour Urine Parameters: A Retrospective Cohort Study. Kidney360. 2025. doi:10.34067/KID.0000000728
- Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nature Medicine. 2025. doi:10.1038/s41591-024-03412-w
- Paik JM, Tesfaye H, Curhan GC, et al. Sodium-Glucose Cotransporter 2 Inhibitors and Nephrolithiasis Risk in Patients With Type 2 Diabetes. JAMA Internal Medicine. 2024. doi:10.1001/jamainternmed.2023.7660
- Pischetola A, Esperto F, Tsaturyan A, et al. Sodium-glucose cotransporter 2 inhibitors vs. glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors for incident and recurrent urolithiasis: a European Association of Urology Endourology systematic review. Translational Andrology and Urology. 2026. doi:10.21037/tau-2026-0541
- Danau RA, Munteanu MA, Mitel A, et al. Urinary Stone Recurrence After Initiation of GLP-1-Based Therapy: A Romanian Retrospective Cohort Study of Clinical, Renal, and Hydration-Related Factors. Journal of Clinical Medicine. 2026. doi:10.3390/jcm15208039
- National Institute of Diabetes and Digestive and Kidney Diseases. Definition & Facts for Kidney Stones. niddk.nih.gov
- National Institute of Diabetes and Digestive and Kidney Diseases. Eating, Diet, & Nutrition for Kidney Stones. niddk.nih.gov
- WEGOVY (semaglutide) prescribing information, section on acute kidney injury due to volume depletion. DailyMed. dailymed.nlm.nih.gov
Medical disclaimer. This article is for general educational and informational purposes only. It is not medical advice and not a substitute for a clinician who knows your history. The studies described here used prescribed doses, most are observational, and sub-label "microdose" regimens have not been studied for kidney stone outcomes. GLP-1 medicines are not approved to prevent or treat kidney stones. Talk to your prescriber before starting, changing or stopping any medicine, and seek prompt care for severe flank pain, fever or blood in the urine. Charts show values reported in the cited sources.