Octreotide

Why this drug is interesting

Sulfonylurea poisoning is the ED's most self-defeating hypoglycaemia. Sulfonylureas close the ATP-sensitive potassium channel on the pancreatic beta cell, depolarising it and triggering insulin release. Give a bolus of 50% dextrose and the glucose itself is a secretagogue: the beta cell, still held open by the drug, releases another surge of insulin. The glucose falls again, often lower than before, and the cycle repeats for as long as the drug is present — which for glibenclamide or glimepiride can be a very long time.

Octreotide interrupts the loop upstream. It is a somatostatin analogue and somatostatin's physiological job includes suppressing insulin release. Give it and the beta cell stops responding, the recurrent hypoglycaemia stops, and the dextrose requirement falls.

Pharmacology

Mechanism

Octreotide binds somatostatin receptors (principally SSTR2 and SSTR5) on the pancreatic beta cell, reducing calcium influx and suppressing insulin secretion. It also suppresses growth hormone, glucagon and a range of gut hormones — which is why it works for acromegaly and carcinoid, and why it has gastrointestinal side effects.

In sulfonylurea poisoning, the specificity is fortuitous but precise: the poison acts at the K_ATP channel and octreotide acts downstream of it on secretion, so the antidote does not have to displace or metabolise the drug at all. It simply prevents the pathological output.

The sulfonylurea-like agents

The same mechanism applies to meglitinides (repaglinide, nateglinide), and to trimethoprim–sulfamethoxazole, which has a sulfonylurea-like effect and is a recognised cause of severe hypoglycaemia in its own right.⁵ Octreotide has been used for that too.

Dosing

Adults

The most common regimen in the reviewed adult cases was subcutaneous dosing, primarily 50–100 micrograms per dose, every 6–8 hours.²

Other findings from the same review that are worth knowing at the bedside:²

• No significant difference in duration of therapy or total dose between intermittent subcutaneous and intravenous dosing in adults.
• Treatment of hypoglycaemia and maintenance of euglycaemia were similar across all routes.
• Infusions had similar durations but higher total doses — so a continuous infusion delivers more drug for no evident advantage.
• Higher intermittent bolus doses were associated with shorter durations of therapy.
• Intentional exposures required higher doses and longer treatment than accidental ones.

Children

The most prevalent paediatric regimen was intravenous dosing at 1 microgram/kg.² Fourteen paediatric cases were included in the review.

Endpoint and duration

Octreotide is continued while the sulfonylurea is still exerting an effect — judged by recurrent hypoglycaemia after octreotide wears off, and by the pharmacology of the specific agent. In the systematic review, all patients except two survived without long-term complications, and only three adverse reactions to octreotide were reported across 80 cases.²

Managing the poisoning around it

1. Treat the acute hypoglycaemia with glucose — orally if safe, intravenously if not. This is necessary and immediate; the point is that it is not sufficient.
2. Avoid repeated large dextrose boluses where you can. Each one is a secretagogue stimulus. A background infusion of 10% glucose with frequent monitoring is generally preferable to serial 50% boluses.
3. Give octreotide — 50–100 micrograms subcutaneously in an adult — once the pattern of recurrent hypoglycaemia is apparent, or earlier in a significant deliberate ingestion.
4. Consider activated charcoal. The 2026 CTRC guideline recommends it for sulfonylureas above an ingested dose of 5 maximal therapeutic doses, with an additional dose below 9 TD; multiple-dose charcoal is weakly recommended against.⁴
5. Check the renal function. Sulfonylurea clearance and duration depend on it, and the elderly patient with an acute kidney injury on gliclazide is the classic therapeutic — not overdose — presentation.
6. Admit. Not for observation in the department; for at least 24 hours of monitored glucose, longer for long-acting agents, modified-release preparations, renal impairment or deliberate ingestion.
7. Ring NPIS on 0344 892 0111 — octreotide use here is off-label, and the observation period depends on the specific agent.

The other drug in this space

Glucagon raises glucose by mobilising hepatic glycogen, and is useful acutely — but it is short-lived, useless once glycogen is depleted, and it is itself an insulin secretagogue, so it does not solve the sulfonylurea problem. Octreotide and glucagon do different jobs.

Safety

Octreotide is a chronic-use drug with a chronic-use side effect profile; single or short-course antidotal use is comparatively benign — three adverse reactions across 80 published cases.² The label's relevant cautions are:

Gastrointestinal

Abdominal pain, nausea, diarrhoea, steatorrhoea, flatulence — common and dose-related, and the usual reason for intolerance

Gallbladder

Gallstones are a well-recognised effect of prolonged therapy through inhibition of gallbladder motility — a chronic-therapy problem, not an acute one

Glucose regulation

Because it suppresses insulin, glucagon and growth hormone, octreotide can cause hyperglycaemia as well as hypoglycaemia, and hypoglycaemia is itself a common labelled adverse reaction. See the callout below — the label describes a mechanism by which octreotide can make hypoglycaemia worse

Bradycardia

A common labelled adverse reaction, alongside QT prolongation and AV block. The label warns that dose adjustment of beta blockers and calcium channel blockers may be necessary — directly relevant if the overdose is a mixed one

Injection site

Pain and irritation, reduced by allowing the solution to reach room temperature

Evidence and critical appraisal

The evidence for octreotide in sulfonylurea poisoning is better than for most antidotes on this site, and still not strong. A 2010 review in the Journal of Medical Toxicology assembled the components: an animal model showing reduced refractory hypoglycaemic episodes, published case reports of prevented recurrence, a retrospective case series showing fewer dextrose boluses and fewer hypoglycaemic events, and two prospective controlled trials showing that octreotide with supplemental dextrose raised blood glucose with fewer hypoglycaemic events. Its conclusion was that there is "sufficient evidence to recommend the use of octreotide with supplemental dextrose".³

The 2025 systematic review then addressed the dose, and found chaos — 41 regimens across 80 patients — with no evident difference in efficacy or safety between them.² Two useful signals emerged: infusions cost more total drug for no gain, and higher intermittent boluses shortened treatment. Neither is a randomised comparison.

The awkwardness is regulatory rather than clinical. A well-supported, low-harm, widely used antidotal indication has never made it into a licence, so every UK administration is off-label, every dose comes from case literature, and the hospital's own guideline — where one exists — is doing the work a label would normally do. That pattern recurs across this batch: see pyridoxine and levocarnitine.

References

1. 1
   Octreotide 100 micrograms/1 ml Solution for Injection — Summary of Product Characteristics. electronic Medicines Compendium, product 373. Section 4.1 verified 31 Aug 2026: the licensed indications are acromegaly, functional GEP endocrine tumours, prevention of complications following pancreatic surgery, emergency control of variceal bleeding and TSH-secreting pituitary adenomas. Hypoglycaemia and sulfonylurea poisoning do not appear. Eighteen octreotide products were listed on the emc at that date; the licensed indications are materially the same across the immediate-release injections.
2. 2
   Ryan E, Rushton W. Variations in octreotide dosing in published reports of sulfonylurea toxicity: a systematic review, 1988–present. Journal of Medical Toxicology 2025;21(2):260–275. PubMed 39821850. 80 patients, 61 sources, 41 dosing strategies. Source of the 50–100 microgram subcutaneous 6–8 hourly adult regimen, the 1 microgram/kg intravenous paediatric regimen, the infusion and bolus findings and the safety figures.
3. 3
   Dougherty PP, Klein-Schwartz W. Octreotide's role in the management of sulfonylurea-induced hypoglycemia. Journal of Medical Toxicology 2010;6(2):199–206. PubMed 20352540. Source of the evidence summary including the two prospective controlled trials and the recommendation for octreotide with supplemental dextrose.
4. 4
   Wang C, Fang W, Li Z, Sun L. Clinical features, risk factors, diagnosis, and treatment of trimethoprim-sulfamethoxazole-induced hypoglycaemia. Frontiers in Endocrinology 2023;14:1059522. PubMed 36843590. Systematic review of case reports; the source for co-trimoxazole's sulfonylurea-like hypoglycaemia. Reference ³ does not cover this — its scope is sulfonylureas only.
5. 5
   Hoegberg LCG, Gosselin S, Buckley NA, Wood DM, et al. Recommendations from the Clinical Toxicology Recommendations Collaborative on the administration of activated charcoal in acute oral overdose. Clinical Toxicology 2026;64(6):419–475. PubMed 41906697. Table 4: sulfonylurea single-dose threshold 5 maximal therapeutic doses, additional dose <9 TD, GRADE D. Full text read 4 Sep 2026.
6. 6
   National Poisons Information Service. TOXBASE · NPIS 0344 892 0111. Required: octreotide for hypoglycaemia is off-label in the UK, and the observation period depends on the specific sulfonylurea.