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Three Part Question

In [patients with sulphonyluria overdose] does [octreotide acetate] prevent [rebound hypoglycemia]

Clinical Scenario

56-year-old man known to have non-insulin dependent diabetes mellitus presents to the Emergency Department after taken an overdose of his own oral hypoglycaemic - Glipizide. The initial blood sugar was very low; therefore he was given a 50 ml bolus of 50% dextrose. The patient recovered but despite a continuous intravenous infusion of 10% dextrose, hypoglycemia recurred. You know that intra-venous dextrose stimulates insulin release, and that sulfhonylurea compounds have a long half-life. You wonder about the use of the somatostatin analogue octreotide, which causes marked suppression of serum immunoreactive insulin and C-peptide concentration, and whether it is safe and effective under such circumstances.

Search Strategy

Medline 1950 to April 07 using Ovid interface
The Cochrane Library issue 2 2007
Medline:[ exp.hypoglycemia or rebound hypoglycaemia. mp] AND [exp. Hypoglycaemic agent/ or Sulfonylurea compounds/ or sulfonylurea overdose.mp or sulfonylurea poisoning.mp] AND [exp octreotide acetate or octreotide .mp] and LIMIT to human AND English.
The Cochrane Library: Exp hypoglycemia {MeSH}and exp sulfonylurea compounds {MeSH] and exp octreotide [MeSH].

Search Outcome

No relevant papers found on Cochrane library. Altogether 14 papers were identified of only 2 were directly relevant to the question. These are summarised in the table below:

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Boyle et al, 1993, New Mexico	8 healthy volunteers, age range 18-50 years given 1.45 mg/kg Glipizide When glucose had dropped to 50 mg/dL then 50 ml 50% glucose was given followed by either variable dextrose infusion or octreotide. At 5h a second 50% glucose bolus was administered and the time to return to target glucose level was measured	Experimental study on healthy volunteers	Time to return to target glucose level of 85 mg/dl after second 50% glucose bolus	3 h vs 6.5h (p=0.001)	Small number, experimental study Not blinded, subject to bias
McLaughlin et al, 1999, New Mexico	9 patients of whom 6 had taken a Glyburide OD and 3 a Glipizide OD. Age range 20-65 yrs	Observational	Mean number of episodes of hypoglycemia before and after treatment with octreotide	3.2 vs 0.2 (p=0.008)	Retrospective chart review design Sample size small
			Mean number of ampoules of 50% dextrose before and after treatment with octreotide	2.9 vs 0.2 (p=0.004)

Comment(s)

There are very few reports and most of them are reviews, case reports and letters. Each of these studies has small numbers of patients. It is difficult to recruit a large series of patients in a single centre. A large multicentre study is needed.

Clinical Bottom Line

Octreotide may be safe and effective in preventing rebound hypoglycaemia in sulphonlyurea overdose. Octreotide in combination with dextrose can be considered for first-line therapy in treatment of sulphonlyurea-induced hypoglycaemia

References

1. Boyle PJ, Justice K, Krentz AJ, Nagy RJ, Schade DS. Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonylurea overdoses. Journal of clinical Endocrinology and Metabolism 1993:76(3);752-756.
2. McLaughlin SA, Crandall CS, McKinney PE. Octreotide: an antidote for sulfonylurea-induced hypoglycemia. Annals of Emergency Medicine 2000:36(2);133-138.