In obese kidney stone formers, weight loss with glucagon-like peptide-1 (GLP)-based therapy was associated with a significant decline in 24-hour urine oxalate and sulfate excretion rates.

Weight loss through GLP-based therapies was associated with nonsignificant changes in urine saturation indices.

In obese kidney stone formers, GLP-based therapy appears to be a safe option for weight loss on the basis of 24-hour urine studies.

BackgroundObesity is an independent risk factor of incident and recurrent nephrolithiasis. The effect of weight loss through glucagon-like peptide 1 (GLP-1) receptor agonists and dual GLP-1/gastric inhibitory polypeptide receptor agonists (GLP-based therapies) on nephrolithiasis is not well understood. This study examined the changes in 24-hour urine chemistry assessing for stone risk during weight loss through GLP-based therapies.MethodsThis retrospective analysis identified adult stone formers followed at our academic institution's weight wellness clinic between September 2015 and August 2023 and included patients with at least two 24-hour urine collections for stone risk assessment. 24-hour urine parameters before and during weight loss in patients on GLP-based therapies were compared.ResultsForty-four obese patients with nephrolithiasis experienced significant weight reduction (−6.6±7.3 kg, P < 0.001) over a median 1.1 years of follow-up with GLP-based therapies. During this period, there was a significant decrease in 24-hour urine oxalate (40±16 to 32±11 mg/d, P = 0.002), sulfate (21±10 to 17±9 mmol/d, P = 0005), and ammonium (35±22 to 29±15 mEq/d, P = 0.01) excretion rates. There were nonsignificant changes in urine calcium, citrate, uric acid, pH, phosphorus, sodium, potassium, magnesium, chloride, creatinine, or total volume. In addition, there was no statistical difference in urine supersaturation indices with respect to calcium oxalate, calcium phosphate, and uric acid.ConclusionsOur results indicate that weight loss through GLP-based therapies is not associated with prolithogenic changes in 24-hour urine chemistry in patients with nephrolithiasis, unlike what happens with other weight loss modalities.

2017-07-01·CNS Drugs2区 · 医学

The Molecular Mechanism of Glucagon-Like Peptide-1 Therapy in Alzheimer’s Disease, Based on a Mechanistic Target of Rapamycin Pathway

2区 · 医学

Article

作者: Li, Lin

The mechanistic target of rapamycin (mTOR) is an important molecule that connects aging, lifespan, energy balance, glucose and lipid metabolism, and neurodegeneration. Rapamycin exerts effects in numerous biological activities via its target protein, playing a key role in energy balance, regulation of autophagy, extension of lifespan, immunosuppression, and protection against neurodegeneration. There are many similar pathophysiological processes and molecular pathways between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), and pharmacologic agents used to treat T2DM, including glucagon-like peptide-1 (GLP-1) analogs, seem to be beneficial for AD. mTOR mediates the effects of GLP-1 analogs in the treatment of T2DM; hence, I hypothesize that mTOR is a key molecule for mediating the protective effects of GLP-1 for AD.

2011-07-01·Gastroenterology1区 · 医学

Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1–Based Therapies

1区 · 医学

Article

作者: Peter C. Butler ; Michael Elashoff ; Aleksey V. Matveyenko ; Belinda Gier ; Robert Elashoff

BACKGROUND & AIMSGlucagon-like peptide-1-based therapy is gaining widespread use for type 2 diabetes, although there are concerns about risks for pancreatitis and pancreatic and thyroid cancers. There are also concerns that dipeptidyl peptidase-4 inhibitors could cause cancer, given their effects on immune function.METHODSWe examined the US Food and Drug Administration's database of reported adverse events for those associated with the dipeptidyl peptidase-4 inhibitor sitagliptin and the glucagon-like peptide-1 mimetic exenatide, from 2004-2009; data on adverse events associated with 4 other medications were compared as controls. The primary outcomes measures were rates of reported pancreatitis, pancreatic and thyroid cancer, and all cancers associated with sitagliptin or exenatide, compared with other therapies.RESULTSUse of sitagliptin or exenatide increased the odds ratio for reported pancreatitis 6-fold as compared with other therapies (P<2×10(-16)). Pancreatic cancer was more commonly reported among patients who took sitagliptin or exenatide as compared with other therapies (P<.008, P<9×10(-5)). All other cancers occurred similarly among patients who took sitagliptin compared with other therapies (P=.20).CONCLUSIONSThese data are consistent with case reports and animal studies indicating an increased risk for pancreatitis with glucagon-like peptide-1-based therapy. The findings also raise caution about the potential long-term actions of these drugs to promote pancreatic cancer.

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