Semaglutide Initiation Linked to Life-Threatening Lactic Acidosis in an Elderly Patient: Case Report
USA: A recent case report published in Case Reports in Critical Care highlights a serious and potentially fatal complication (lactic acidosis) following the initiation of semaglutide in an elderly patient with long-standing diabetes. The report, authored by Zhanna Albany and colleagues from the Indiana University School of Medicine, highlights the need for heightened vigilance when combining newer glucose-lowering agents with existing therapies such as metformin.
Glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide, are increasingly prescribed due to their benefits in glycemic control and weight reduction. However, gastrointestinal side effects such as nausea, vomiting, and reduced oral intake are common and may have significant downstream consequences—particularly in older adults with multiple comorbidities and complex drug regimens.
The authors describe the case of a 77-year-old man with a more than three-decade history of type 2 diabetes who presented to the emergency department with altered mental status, severe hypoglycemia, and signs of dehydration. Three weeks prior, semaglutide had been initiated at a low dose for weight management, replacing glimepiride. Soon after starting therapy, the patient experienced persistent nausea, worsening vomiting, and poor oral intake, eventually leading to significant weight loss and clinical deterioration.
On admission, he exhibited hallmark features of severe metabolic acidosis, including rapid, deep breathing consistent with Kussmaul respiration. Laboratory evaluation revealed profound abnormalities, including markedly elevated lactate levels, severe acidemia, acute kidney injury, and critically low blood glucose. Importantly, there was no evidence of infection, cardiac dysfunction, or other common causes of tissue hypoxia.
The clinical picture pointed toward metformin-associated lactic acidosis, a rare but life-threatening condition. In this case, dehydration triggered by semaglutide-induced gastrointestinal symptoms likely precipitated acute kidney injury, impairing the clearance of both metformin and lactate. This resulted in a dangerous cycle of metabolic derangement.
The patient required intensive care management, including bicarbonate infusion and urgent hemodialysis. Following treatment, his metabolic parameters improved rapidly, and he made a full recovery. At follow-up, kidney function and lactate levels had normalized.
This case brings attention to several important clinical considerations. Elderly patients appear particularly vulnerable to dehydration when treated with GLP-1 receptor agonists. When combined with medications such as metformin, insulin, diuretics, or antihypertensives, the risk of adverse outcomes may increase due to overlapping effects on fluid balance and renal function.
The authors emphasize the importance of close clinical and biochemical monitoring when initiating semaglutide, especially in patients with polypharmacy. Early recognition of warning signs, such as persistent vomiting or Kussmaul breathing, can be critical. Additionally, educating patients about temporarily withholding metformin during periods of acute illness or reduced intake—the so-called “sick day rule”—may help prevent such complications.
As the use of GLP-1 therapies continues to expand, this report serves as an important reminder that even well-established medications like metformin can become hazardous under certain clinical conditions.
Reference:
Albany, Z., Roe, D., Gutteridge, D., Webb, H., & Kara, A. (2025). Two Doses to ICU or When Lactate Equals Glucose: Life-Threatening Lactic Acidosis due to Metformin After Initiation of Semaglutide. Case Reports in Critical Care, 2026(1), 3478800. https://doi.org/10.1155/crcc/3478800
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