Hypoglycemia after bariatric surgery: Management updates

Anira Iqbal; Vinni Makin

doi:10.3949/ccjm.92a.24033

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TABLE 1

Medications for managing post–bariatric surgery hypoglycemia: Mechanisms of action

Medication	Mechanism of action
Acarbose^8,23,25,26	Inhibits intestinal alpha-glucosidase—delays absorption of glucose from the intestine, decreases postprandial glycemic and insulinemic peaks
Diazoxide^26–28	Reduces insulin secretion by inhibition of beta-cell adenosine triphosphate–sensitive potassium channels, induces hepatic gluconeogenesis
Octreotide, pasireotide^25,26,29	Somatostatin analogs delay gastric emptying, reduce insulin and GLP-1 secretion
Nifedipine or verapamil^25,30	Inhibits insulin release by inhibiting calcium channels in pancreatic beta cells
GLP-1 analogs^25,26,31	Decreases variability in GLP release, which causes synchronous insulin and glucose peaks, delays gastric emptying, decreases appetite, stimulates glucagon secretion
Dipeptidyl peptidase 4 inhibitors^25,26	Reduces the degradation of GLP-1 and glucose-dependent insulinotropic polypeptide and raises their levels
GLP-1 antagonist^32–34	Prevents surges in GLP-1 and insulin, increases glucagon secretion
SGLT-2 inhibitors^35,36	Reduces carbohydrate absorption by inhibiting intestinal SGLT-1 and increasing hepatic glucose production
Interleukin 1 beta antagonist (anakinra)³⁷	Decreases dysregulated proinflammatory signaling, which can cause excessive insulin response
Glucagon^38,39	Glucagon receptor agonist, stimulates glycogenolysis and hepatic gluconeogenesis
Insulin receptor antibody (XOMA 358)^40,41	Reverses insulin-induced hypoglycemia by significantly decreasing insulin sensitivity and increasing hepatic glucose output

GLP = glucagon-like peptide; SGLT = sodium-glucose cotransporter

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TABLE 2

Medications for managing post–bariatric surgery hypoglycemia: Dosages and side effects

Medication	Dosage	Side effects	Notes
Acarbose^8,23,25,26	25 mg with 1 meal per day, slowly titrate up to 100 mg at every meal daily	Bloating, abdominal cramping, diarrhea	Used as first line because it’s affordable and available Not recommended in significant renal impairment If hypoglycemia occurs, correct with simple carbohydrates (glucose, dextrose, honey)—complex carbohydrates (table sugar, juice, soft drink, candy) will not be effective
Diazoxide^26–28	50–100 mg twice daily to start	Fluid retention, edema, nausea, hypotension, hirsutism, headache	Consider dose reduction with renal impairment Typically used for hypoglycemia from insulinomas Affordability and insurance coverage are barriers
Octreotide, pasireotide^25,26,29	Octreotide 25–100 μg SC before meals Octreotide long-acting repeatable 20-mg intramuscular injection monthly Pasireotide 50–300 μg SC before meals or 300 μg SC daily	Diarrhea, steatorrhea, cholelithiasis, hyperglycemia (more with pasireotide), QT prolongation	Safe to use in renal impairment Expensive Screening abdominal ultrasonography and electrocardiogram required Pasireotide is longer acting than octreotide and is available for compassionate use in severe PBH Oral octreotide is available but has not been used for this indication
Nifedipine or verapamil^25,30	Verapamil 40 mg 3 times daily Nifedipine 30–60 mg daily	Hypotension, edema	Safe to use in renal impairment
GLP-1 analogs^25,26,31	Liraglutide 0.6 mg titrated to 1.2 mg SC daily, up to 1.8 mg daily	Nausea, constipation	Contraindicated in patients with family or personal history of medullary thyroid carcinoma Use with caution in patients with history of pancreatitis Safe to use in renal impairment but avoid dehydration Expensive
Dipeptidyl peptidase 4 inhibitors^25,26	Sitagliptin 100 mg once daily	Nausea, constipation	Inconclusive results—not recommended
GLP-1 antagonist^32–34	Avexitide 30 mg SC twice daily	Headache, nausea, injection-site reaction	Recently granted breakthrough therapy designation by the US Food and Drug Administration for treating PBH and congenital hyperinsulinism, currently in phase 3 trial
SGLT-2 inhibitors^35,36	Canagliflozin 100 or 300 mg daily Empagliflozin 10–25 mg daily	Dehydration, urinary tract and genital mycotic infections, euglycemic diabetic ketoacidosis	Dosage adjustment required in renal impairment Canagliflozin and empagliflozin shown to improve glycemic response to oral glucose tolerance and mixed meal tolerance tests, respectively, in patients with PBH
Interleukin 1 beta antagonist³⁷	Anakinra 100 mg SC daily		Anakinra and SGLT-2 inhibitor empagliflozin reduced the number of hypoglycemic events during a liquid mixed meal test
Glucagon^38,39	Dasiglucagon 80 or 120 μg SC injection as needed for hypoglycemia	Nausea, vomiting, hyperglycemia, reduced appetite	Still under clinical investigation, use of glucagon in an insulin pump has shown satisfactory results May be used for treatment of acute severe hypoglycemia
Insulin receptor antibody^40,41	XOMA 358 3–9 mg/kg daily	Headache, hyperhidrosis	Results from phase 2 trial not announced yet