GLP-1 Microdosing and Kidney Stones: Weight Loss, Urine Chemistry, and What the Cohort Data Shows

Do GLP-1 medicines raise or lower the risk of kidney stones? The evidence points both ways, and neither direction is proven. Excess weight clearly raises stone risk, so losing it should help. Yet one large Veterans Affairs study linked GLP-1 use with more kidney stones, while urine studies in stone formers on these drugs found no stone-promoting changes.

Kidney stones are common enough that the question matters. In the 2017-2018 round of the US National Health and Nutrition Examination Survey, 10.9% of men and 9.5% of women reported having had a stone, and the figure among women rose from 6.5% to 9.4% over a decade. Obesity was one of the factors linked with higher prevalence.

This article covers why body weight and stones are connected, what 24-hour urine studies show in people on semaglutide and tirzepatide, why GLP-1 drugs look worse than SGLT2 inhibitors in diabetes cohorts, and where fluid intake fits. No study has looked at kidney stones on microdose regimens, and that gap runs through everything below.

Does excess weight raise the risk of kidney stones?

The starting point for every GLP-1 user

Yes. Higher body weight, weight gain and a larger waist are each linked with more kidney stones, and the link looks stronger in women. The clearest data come from Taylor, Stampfer and Curhan, who followed 45,988 men in the Health Professionals Follow-up Study and 93,758 and 101,877 women in the two Nurses' Health Studies, and reported in JAMA in 2005. They documented 4827 new stones over a combined 46 years of follow-up.

After adjusting for diet, fluid intake and other factors, men weighing more than 220 lb (100.0 kg) had a relative risk of 1.44 compared with men under 150 lb (68.2 kg). The equivalent figures were 1.89 in older women and 1.92 in younger women. Weight gain counted too: men who had gained more than 35 lb (15.9 kg) since early adulthood had a relative risk of 1.39, and women 1.70 and 1.82.

The authors concluded that obesity and weight gain increase the risk of stone formation, and that the effect may be larger in women. That baseline matters for anyone on a GLP-1 protocol: many people start with a body size that already carries extra stone risk, before any drug effect is considered.

What happens to urine chemistry during weight loss on a GLP-1?

The 24-hour urine studies

In the two 24-hour urine studies published so far, GLP-1 therapy did not push urine chemistry toward stone formation. A 24-hour urine collection measures the minerals and volume that determine whether crystals can form, so it is the standard test for stone risk in people who have already had one.

Feghali, Li and Maalouf at UT Southwestern reviewed 44 obese stone formers treated with GLP-1 receptor agonists or the dual GLP-1/GIP agonist tirzepatide at a weight clinic between 2015 and 2023, publishing in Kidney360 in 2024. Over a median 1.1 years, the group lost an average of 6.6 kg. Urine oxalate fell from 40 to 32 mg per day, sulfate from 21 to 17 mmol per day, and ammonium from 35 to 29 mEq per day.

Calcium, citrate, uric acid, pH and total urine volume did not change significantly, and neither did supersaturation for calcium oxalate, calcium phosphate or uric acid. The authors wrote that weight loss through GLP-based therapy was not linked with stone-promoting changes, unlike what happens with other weight-loss methods. Lower oxalate is a plausible benefit, since calcium oxalate is the most common stone type, but the study did not count stones.

A larger Medicare study by Schaub and colleagues, in Kidney360 in 2025, compared 349 stone formers with diabetes who filled a GLP-1 prescription with 349 matched controls. There were no significant differences in any urine parameter, and a longitudinal group of 154 people who started a GLP-1 between two collections showed none either. The authors put it plainly: GLP-1 drugs were not linked with changes that would reduce stone risk. Neutral, in other words, rather than protective.

Why did a large VA study link GLP-1 drugs with more kidney stones?

A signal from a discovery analysis

The Veterans Affairs study found a statistical association, not proof that the drugs cause stones. Xie, Choi and Al-Aly, writing in Nature Medicine in 2025, compared 215,970 veterans with diabetes who started a GLP-1 receptor agonist against 1,203,097 who continued their usual diabetes medicines. They screened 175 health outcomes at once.

GLP-1 use was linked with lower risk of many conditions, including substance use disorders and dementia, and with higher risk of several others: gastrointestinal disorders, low blood pressure, fainting, arthritic disorders, nephrolithiasis, interstitial nephritis and drug-induced pancreatitis. A design that tests 175 outcomes is built to find signals worth following up, and the population was mostly older men with diabetes rather than people using GLP-1 drugs for weight alone.

The low blood pressure and fainting findings in the same list hint at one plausible thread: reduced fluid intake. People on GLP-1 drugs eat less and often drink less, and vomiting or diarrhoea adds losses. Concentrated urine is a classic setting for crystals to form. Our guide to hydration and electrolytes on a GLP-1 protocol covers why fluid intake tends to fall with food volume. That explanation remains a hypothesis; the urine studies above did not find lower urine volume.

Are SGLT2 inhibitors better than GLP-1 drugs for kidney stone risk?

What the diabetes cohorts compare

In people with type 2 diabetes, SGLT2 inhibitors are linked with fewer kidney stones than GLP-1 drugs, most likely because SGLT2 inhibitors actively protect rather than because GLP-1 drugs harm. In the EMPRISE cohort, reported by Tesfaye and colleagues in Diabetes, Obesity and Metabolism in 2025, 130,125 matched pairs started either empagliflozin or a GLP-1 receptor agonist. Over about 8 months on treatment there were 1,399 stone events on empagliflozin and 1,825 on GLP-1 drugs, a hazard ratio of 0.71 and 6.48 fewer events per 1,000 person-years.

A TriNetX study by Liu and colleagues, in Kidney360 in 2026, matched 371,374 pairs and found new stones in 1.6% of SGLT2 inhibitor users and 2.0% of GLP-1 users, a hazard ratio of 0.812. Both studies found almost the same advantage for SGLT2 inhibitors against DPP4 inhibitors, a third diabetes drug class not known to affect stones (hazard ratios of 0.75 and 0.825). That pattern suggests the SGLT2 drugs are lowering risk, not that GLP-1 drugs are unusually raising it.

The Medicare urine study explains the mechanism. Stone formers on SGLT2 inhibitors had higher urine citrate, 838 versus 636 mg per day, and higher volume, 2.4 versus 2.0 L, than controls. Citrate blocks calcium crystals and volume dilutes them. GLP-1 users showed neither change. Our article on combining SGLT2 inhibitors and GLP-1s covers what the two classes do together.

How does the kidney stone risk compare with bariatric surgery?

Why the weight-loss method matters

Bariatric surgery carries a far clearer stone risk than anything reported for GLP-1 drugs. A Mayo Clinic study by Lieske and colleagues, in Kidney International in 2015, matched 762 surgical patients with equally obese controls. Over 6.0 years, 11.0% of the surgery group formed a new stone compared with 4.3% of controls. Standard gastric bypass carried an adjusted hazard ratio of 2.13 and more malabsorptive procedures 4.15, while purely restrictive surgery showed no significant change.

The Scandinavian Obesity Surgery Registry, analysed by Laurenius and colleagues in Obesity Surgery in 2023, compared 58,366 surgical patients with 583,660 population controls. Gastric bypass had a hazard ratio of 6.16, sleeve gastrectomy 6.33 and biliopancreatic diversion with duodenal switch 10.16. The contrast with the Feghali data is the useful part: weight loss itself does not automatically raise stone risk, and the route to weight loss shapes what happens in the urine.

Does drinking more water prevent kidney stones on a GLP-1?

The best-supported habit

Higher fluid intake is the most consistently supported way to lower stone risk in general, though it has not been tested specifically in GLP-1 users. A meta-analysis by Cheungpasitporn and colleagues in the Journal of Nephrology in 2016 pooled 9 studies: 2 randomized trials with 269 patients and 7 observational studies with 273,685 people. High fluid intake was linked with a risk ratio of 0.40 for stones in the trials and 0.49 in the observational studies, and 0.20 for recurrent stones in the observational data.

A 2026 systematic review in Annals of Internal Medicine by Asher and colleagues, covering 31 studies including 26 randomized trials, reached a similar view with appropriate caution. For adults with calcium oxalate or calcium phosphate stones, more fluid, a diet with normal to high calcium and low protein and sodium, and certain medicines may prevent recurrence. The authors rated that evidence as low strength.

For someone on a GLP-1 protocol, the practical point is that thirst and meal-linked drinking both tend to drop, so fluid intake may need to be deliberate rather than automatic. The diet advice also overlaps with GLP-1 eating patterns: normal calcium intake is protective, so cutting dairy to save calories is not a stone-friendly choice. Uric acid stones share risk factors with gout, which our article on uric acid during rapid weight loss covers.

Does a GLP-1 microdose change kidney stone risk?

What can and cannot be said

Nobody knows, because no study has measured kidney stones at microdose levels. Every number in this article comes from people with diabetes or obesity on standard doses, and most of the cohort data come from people with diabetes, who already carry higher stone risk.

Two lines of reasoning point in opposite directions, and both are untested. A lower dose usually means milder appetite suppression and fewer gut side effects, which could mean less disruption to fluid intake. A lower dose also tends to mean less weight loss, so any benefit from reduced oxalate or body weight would likely be smaller.

The practical steps do not depend on resolving that. Anyone with a past stone should mention it before starting a GLP-1 at any dose, keep fluid intake deliberate on low-appetite days, and replace fluids promptly after vomiting or diarrhoea. Stone formers under specialist care can ask whether a repeat 24-hour urine collection after weight loss would be useful. For other effects of shrinking meals, see our article on micronutrient status on a GLP-1 protocol.

Frequently Asked Questions