Octreotide;

My hospitalized patient with acute kidney injury and type 2 diabetes is persistently hypoglycemic, likely related to sulfonylurea use. Is there a role for octreotide?

FA Manian MD, MPH, , , , , , , , , , , , , , Leave a comment

Yes, octreotide is indicated in the treatment of sulfonylurea-induced hypoglycemia1.

Sulfonylureas are widely used in the treatment of type 2 diabetes mellitus. Hypoglycemia is a known potential adverse effect which may be prolonged and recurrent, and last for days after ingestion.1,2 The risk is higher in elderly patients, renal or hepatic dysfunction, alcohol use, and polypharmacy, as observed with certain antibiotics.3,4

The mode of action of sulfonylureas is through binding to SUR1 receptors on the pancreatic β-cell membrane which leads to an inhibition of ATP-dependent potassium efflux channels. This results in membrane depolarization, opening voltage-gated calcium channels which in turn triggers insulin release.1 Sulfonylureas are metabolized in the liver and are renally cleared, thus hepatorenal dysfunction can increase the magnitude and duration their action.2  Octreotide binds to somatostatin receptors on pancreatic β-cells, which closes the voltage-gated calcium channels, preventing insulin release.1

Treatment for sulfonylurea-induced hypoglycemia begins with carbohydrate administration, with oral glucose or IV dextrose boluses and infusion.1 Octreotide should be used in acute overdose as well in refractory hypoglycemia.5 In fact, the administration of carbohydrates can cause a transient hyperglycemia which potentiates further insulin release, leading to recurrent rebound hypoglycemia.1

Octreotide can be given subcutaneously or IV with equivalent bioavailability. The typical dose is 50-100 micrograms every 6-12 hours, with 12-72 hours of therapy usually considered adequate. Serum glucose should be closely monitored during treatment and at least for 16-24 hours afterwards. The good news is that octreotide is generally well tolerated, and, in most cases, adverse effects are mild including hyperglycemia, injection site pain, and GI upset.1,2,5

Bonus Pearl:

Did you know that sulfonylureas are also widely used as herbicides? Herbicidal sulfonylureas disrupt the synthesis of branched chain amino acids via inhibition of AHAS, an enzyme present in plants, bacteria, and fungi. There is low toxicity to humans and animals as our bodies lack this enzyme.6

Contributed by Tony Hiran, MD, Mercy Hospital, St. Louis, MO

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References

  1. Dougherty PP, Klein-Schwartz W. Octreotide’s role in the management of sulfonylurea-induced hypoglycemia. J Med Toxicol 2010;6:199-206. doi: 10.1007/s13181-010-0064-z. PMID: 20352540; PMCID: PMC3550273.
  2. Gonzalez RR, Zweig S, Rao J, Block R, Greene LW. Octreotide therapy for recurrent refractory hypoglycemia due to sulfonylurea in diabetes-related kidney failure. Endocr Pract 2007;13:417-23. doi: 10.4158/EP.13.4.417. PMID: 17669721.
  3. Harrigan RA, Nathan MS, Beattie P. Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity, and treatment. Ann Emerg Med 2001; 38:68-78. doi: 10.1067/mem.2001.114314. PMID: 11423816.
  4. Pearls4Peers. My patient is being treated for a urinary tract infection with trimethoprim-sulfamethoxazole (TMP-SMX) and has developed hypoglycemia — can it be related? Pearls4Peers. 2016 Jul 27. Available from: https://pearls4peers.com/2016/07/27/my-patient-is-being-treated-for-a-urinary-tract-infection-with-trimethoprim-sulfamethoxazole-tmp-smx-and-has-developed-hypoglycemia-can-it-be-related/ [Accessed 1st January 2026].
  5. Glatstein M, Scolnik D, Bentur Y. Octreotide for the treatment of sulfonylurea poisoning. Clin Toxicol (Phila) 2012;50:795-804. doi: 10.3109/15563650.2012.734626. Epub 2012 Oct 10. PMID: 23046209.
  6. Lonhienne T, Garcia MD, Pierens G, Mobli M, Nouwens A, Guddat LW. Structural insights into the mechanism of inhibition of AHAS by herbicides. Proc Natl Acad Sci U S A. 2018;115:E1945-E1954. doi: 10.1073/pnas.1714392115. Epub 2018 Feb 13. PMID: 29440497; PMCID: PMC5834681.

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My hospitalized patient with acute kidney injury and type 2 diabetes is persistently hypoglycemic, likely related to sulfonylurea use. Is there a role for octreotide?

Should I consider octreotide in my patient with non-variceal upper GI bleed?

FA Manian MD, MPH, , , , , , Leave a comment

Octreotide is routinely used in the treatment of variceal bleeding due to its vasoconstrictive effects on the splanchnic vasculature.1 In non-variceal upper GI bleed (NVUGB), however, the evidence for routine use of octreotide is hard to come by with an international consensus panel recommending its use only on a case-by-case basis in patients with very active bleeding while awaiting endoscopy or surgery.2,3

These recommendations are based on the failure of several randomized controlled trials in demonstrating the superiority of octreotide in NVUGB over placebo, either alone or with ranitidine, except in a small subset of patients with actively oozing ulcers.4-6 Although a meta-analysis has suggested that octreotide may reduce the risk of continued bleeding in NVUGB,7 the validity of some of the included studies has been questioned.8

On the other hand, octreotide decreases gastric mucosal blood flow and inhibits acid and pepsin secretion, which may potentially benefit patients who are actively bleeding.9

Final fun fact: Did you know that octreotide may be effective in the treatment of chylothorax?

 

References

  1. Avgerinos A, Armonis A, Raptis S. Somatostatin and octreotide in the management of acute variceal hemorrhage. Hepatogastroenterology 1995;42:145-50. http://europepmc.org/abstract/med/7672763
  2. Barkun AN, Barrdou M, Kulpers EJ, et al. International concensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2010;152:101-113. http://annals.org/aim/article/745521/international-consensus-recommendations-management-patients-nonvariceal-upper-gastrointestinal-bleeding
  3. Barkun A, Bardou M, Marshall JK, Nonvariceal Upper GIBCCG Consensus Conference Group. Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2003;139:843–857. https://www.ncbi.nlm.nih.gov/pubmed/14623622
  4. Nikolopoulou VN, Thomopoulos KC, Katsakoulis EC, et al. The effect of octreotide as an adjunct treatment in active nonvariceal upper gastrointestinal bleeding. J Clin Gastroenterol 2004;38:243-7. http://journals.lww.com/jcge/Abstract/2004/03000/The_Effect_of_Octreotide_as_an_Adjunct_Treatment.9.aspx
  5. Archimandritis A, Tsirantonaki M, Tryphonos M, et al. Ranitidine versus ranitidine plus octreotide in the treatment of acute non-variceal upper gastrointestinal bleeding: a prospective randomized study. Curr Med Res Opin. 2000;16(3):178-83. http://www.tandfonline.com/doi/abs/10.1185/0300799009117023
  6. Okan A, Simsek I, Akpinar H, et al. Somatostatin and ranitidine in the treatment of non-variceal upper gastrointestinal bleeding: a prospective, randomized, double-blind, controlled study. Hepatogastroenterology 2000;47:1325-7. http://europepmc.org/abstract/med/11100343
  7. Imperiale TF, Birgisson S. Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Ann Intern Med 1997;127:1062–1071. http://annals.org/aim/article/711021/somatostatin-octreotide-compared-h-2-antagonists-placebo-management-acute-nonvariceal
  8. Palmer KR. Non-variceal upper gastrointestinal haemorrhage: guidelines. Gut. 2002;51 (Suppl 4): iv1–iv6. http://gut.bmj.com/content/51/suppl_4/iv1.short
  9. Sgouros SN, Bergele C, Viazis N, et al. Somatostatin and its analogues in peptic ulcer bleeding: facts and pathophysiological aspects. Dig Liver Dis. 2006;38:143-8. http://www.sciencedirect.com/science/article/pii/S1590865805002434

 

Contributed byAlice Choi, Medical Student, Harvard Medical School

 

Should I consider octreotide in my patient with non-variceal upper GI bleed?

The serum creatinine of my patient originally admitted for management of tense ascites is slowly rising. How concerned should I be?

FA Manian MD, MPH, , , , , , , , Leave a comment

Although the causes of increasing serum creatinine (SCr) in patients with cirrhosis are legion (eg, sepsis, acute tubular injury, and intravascular volume depletion due to over-diuresis, gastrointestinal bleed, or other causes), the most feared cause is often hepatorenal syndrome (HRS). HRS is a functional renal impairment that reflects the final pathophysiological stages of systemic circulatory impairment1, and significantly contributes to a worsening prognosis in patients with cirrhosis2. For example, without treatment, in patients whose SCr doubles in less than 2 weeks (type I HRS) the median survival is less than 2 weeks , while in those who develop a more gradual renal impairment (type II HRS) the median survival is 6 months3.

Physiologically, HRS is a culmination of significant vasodilation in the splanchnic arteries which, in time, leads to reduced organ perfusion due to a drop in the cardiac output. The associated increase in the activity of the renin-angiotensin-aldosterone and the sympathetic nervous systems contributes to sodium and water retention, and further exacerbates intra-renal vasoconstriction and ascites3.

The primary goal in the medical management of HRS is to increase splanchnic vascular resistance4, often by administering a combination of IV albumin, octreotide and other vasoconstricting agents (eg, midodrine, norepinephrine, or terlipressin [unavailable in US and Canada]).  Of interest, in addition to expanding the circulating plasma volume, albumin may have a vasoconstricting effect by binding to endotoxins, nitric oxide, bilirubin and fatty acids4!

 

References

  1. Arroyo V, Fernandez J, Gines P. Pathogenesis and treatment of hepatorenal syndrome. Semin Liver Dis 2008;28:81-95.
  2. Salerno F, Gerbes A, Ginès P, et al. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8.
  3. Cardenas A, Gines P. A Patient with cirrhosis and increasing creatinine Level: What Is It and what to do? Clin Gatroenterol Hepatol 2009;7:1287–1291. 
  4. Baraldi O, Valentini C, Donati G, et al. Hepatorenal syndrome: Update on diagnosis and treatment. World J Nephrol. 2015;4:511-20.

Contributed by Alireza Sameie, Medical Student, Harvard Medical School

The serum creatinine of my patient originally admitted for management of tense ascites is slowly rising. How concerned should I be?