Two patients developed a rare non-insulin-mediated ketotic hypoglycemia after sleeve gastrectomy that didn't respond to dietary changes, but semaglutide (a GLP-1 receptor agonist) resolved or significantly reduced their hypoglycemic episodes.
2 cases resolvedSemaglutide eliminated hypoglycemic episodes in one patient and significantly reduced them in another after dietary management failed
What the researchers found
Two patients developed symptomatic ketotic hypoglycemia after sleeve gastrectomy, characterized by low insulin, low C-peptide, and elevated beta-hydroxybutyrate levels during fasting (at 40 and 65 hours respectively). Morning cortisol and IGF-1 were normal, ruling out adrenal or growth hormone deficiency.
Dietary management was inadequate. Treatment with semaglutide resulted in complete resolution of hypoglycemic episodes in one patient and significant reduction in the other. The mechanism likely involves reduced hepatic, renal, or intestinal gluconeogenesis after bariatric surgery, or a possible unmasked inborn error of metabolism.
Why it matters
Post-bariatric hypoglycemia is a recognized complication, but it's usually driven by hyperinsulinemia (too much insulin). These cases describe a rare and distinct form — ketotic hypoglycemia with appropriately low insulin — that is poorly understood and doesn't respond to standard dietary approaches. The successful use of semaglutide opens a new treatment option for these patients and raises questions about the metabolic consequences of bariatric surgery.
How the study worked
This is a case report describing two patients who developed ketotic hypoglycemia following sleeve gastrectomy. The patients underwent prolonged fasting tests (40 and 65 hours), with measurement of glucose, insulin, C-peptide, beta-hydroxybutyrate, cortisol, and IGF-1. Dietary management was trialed first, followed by semaglutide treatment.
What this study cannot tell us
This is a case report of only two patients, providing the lowest level of clinical evidence. The mechanism by which semaglutide resolves non-insulin-mediated hypoglycemia is not explained and is somewhat paradoxical, since GLP-1 agonists typically enhance insulin secretion. The fasting durations (40 and 65 hours) are extreme and may not reflect typical daily conditions. Underlying inborn errors of metabolism were not definitively excluded through genetic testing.
How to read the evidence
This is a case report of two patients — the lowest tier of clinical evidence. While the outcomes are compelling, case reports cannot establish causation or generalizability and serve primarily as hypothesis-generating observations.
When this study was published
Published in 2025, this is very recent and reflects current clinical experience with both post-bariatric complications and GLP-1 receptor agonist use.
The bigger picture
As bariatric surgery rates continue to rise globally, understanding and managing post-surgical metabolic complications becomes increasingly important. This report identifies a rare subtype of post-bariatric hypoglycemia and, more importantly, demonstrates that a GLP-1 receptor agonist — typically used for diabetes and obesity — can treat it. This adds to the growing list of unexpected therapeutic applications for semaglutide and highlights the complex metabolic rewiring that bariatric surgery causes.
Questions still open
- By what mechanism does semaglutide prevent non-insulin-mediated hypoglycemia when its primary action is to enhance insulin secretion?
- How common is ketotic (non-hyperinsulinemic) hypoglycemia after bariatric surgery, and is it being underdiagnosed?
- Should prolonged fasting tests become standard evaluation for unexplained post-bariatric hypoglycemia?
Common questions
What is ketotic hypoglycemia and how is it different from typical post-bariatric low blood sugar?
Why is it surprising that semaglutide helped with low blood sugar?
Read the original research
Ketotic Hypoglycaemia Following Sleeve Gastrectomy.
Clinical endocrinology, 103(1), 45-49
Citation
He, Jinwen; Phillips, Liza; Nisbet, Janelle; Morton, Adam. (2025). Ketotic Hypoglycaemia Following Sleeve Gastrectomy.. Clinical endocrinology, 103(1), 45-49. https://doi.org/10.1111/cen.15232