What is the relationship between semaglutide (GLP-1 receptor agonist) and dark urine, a potential indicator of impaired renal function or hepatic dysfunction?

From the Guidelines

If you're experiencing dark urine while taking semaglutide, you should contact your healthcare provider promptly as this may indicate a potential liver issue or other medical conditions. Dark urine can be a sign of liver dysfunction, dehydration, or other medical conditions unrelated to the medication. While semaglutide itself is not typically associated with causing dark urine as a common side effect, it could potentially contribute to liver problems that might manifest as dark urine 1. The mechanism behind potential liver effects with GLP-1 receptor agonists like semaglutide isn't fully understood, but these medications are processed through the body and can occasionally affect organ function. Some key points to consider:

• GLP-1 receptor agonists, including semaglutide, have been shown to reduce albuminuria and slow eGFR decline in patients with type 2 diabetes and chronic kidney disease 1.
• Semaglutide has been found to reduce the risk of new or worsening nephropathy in patients with type 2 diabetes 1.
• The most common side effects of GLP-1 receptor agonists are nausea, vomiting, and diarrhea, which can usually be managed with dose titration and may abate over time 1.
• It's essential to stay well-hydrated while taking semaglutide, as the medication can cause gastrointestinal side effects that might lead to dehydration.
• Your doctor may recommend liver function tests to assess for any abnormalities if you're experiencing dark urine while on semaglutide. Don't stop taking semaglutide without medical advice, but do seek prompt evaluation for this symptom.

From the FDA Drug Label

The primary excretion routes of semaglutide-related material are via the urine and feces. Approximately 3% of the dose is excreted in the urine as intact semaglutide.

The FDA drug label does not provide information on the relationship between semeglutide and dark urine.

From the Research

Semaglutide and Dark Urine

There is no direct evidence in the provided studies that links semaglutide to dark urine. However, the following points can be considered:

• Semaglutide is associated with kidney adverse events, including acute kidney injury and acute interstitial nephritis (AIN) 2.
• AIN can cause changes in urine color, but this is not specifically mentioned in the studies.
• Semaglutide can cause gastrointestinal side effects, such as nausea, vomiting, and abdominal pain, which may lead to dehydration and concentrated urine 3.
• Dehydration and concentrated urine can cause dark urine, but this is not a direct effect of semaglutide.

Kidney Function and Semaglutide

The studies suggest that semaglutide can affect kidney function, including:

• Initial reductions in estimated glomerular filtration rate (eGFR) that plateau over time 4, 5.
• Marked reductions in urinary albumin-to-creatinine ratio (UACR) 4, 5.
• No increase in the risk of kidney adverse events compared to active comparators 4.
• Association with AIN and podocytopathy, which can affect kidney function 2.

Adverse Effects of Semaglutide

The studies mention the following adverse effects of semaglutide:

• Gastrointestinal side effects, such as nausea, vomiting, and abdominal pain 3.
• Acute kidney injury and AIN 2.
• Acute pancreatitis, anesthetic risks, acute gallbladder injury, nonarteritic anterior ischemic optic neuropathy, and diabetic retinopathy 6.