Table 2. Pharmacologic therapy for diabetes-related enteropathic diarrhea.

Agents	Mechanism of action	Dosage	Clinical considerations
Available over the counter
Loperamide	μ opioid receptors agonist Increases non-propulsive contractions Decreases longitudinal propulsive peristalsis Provides increased tine for absorption	Initial dose 2 mg once daily Maximum daily dose 16 mg in divided dosing	For doses, less than 2- or 2-mg increments needed, loperamide available as suspension 1 mg/5 mL
Available by prescription only
Bile acid sequestrants (cholestyramine, colestipol, and colesevelam)	Binds bile acids in the small bowel Results in reduction in colonic bile acid (bile acids known for intestinal secretion, increased mucosal permeability, and acceleration of colonic transit)	Cholestyramine 4 g once to twice daily Colestipol 1 g once to twice daily Colesevelam 625 mg three times daily to a maximum daily dose of 3750 mg	This is an off-label use Has benefit of lowering LDL cholesterol and hemoglobin A1c in diabetes Should be taken an hour after or 4–6 h before other medications to as not affect absorption Palatability of cholestyramine can be limiting
Clonidine	Alpha 2-adrenergic agonist Results in inhibition of acetylcholine release from nerves in the myenteric plexus and neuromuscular junction reducing intestinal motility	225 mcg to 700 mcg daily	Decreased stool volume and stool frequency and increased colon transit in several small observational studies and case reports Hypotension, bradycardia, fatigue, dry mouth, and headache can be limiting
Diphenoxylate (marketed as diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg per tablet)	μ opioid receptors agonist Increases non-propulsive contractions Decreases longitudinal propulsive peristalsis Provides increased time for absorption	5 mg (2 tabs) once to maximum of four times daily	Crosses the blood–brain barrier with risk of causing sedation, euphoria, and potentially leading to dependence with chronic use
Octreotide	Reduces release of gut peptides and splanchnic blood flow Results in decreased motility and secretion	Initial dose 100 mcg SQ QD or 50 mcg SQ BID Max dose 100 mcg SQ BID	Evidence in diabetic diarrhea limited to case reports
Ondansetron	Inhibition of the excitatory neurons of the enteric nervous system Results in prolongation of colon transit time	4–8 mg TID	One case report of use in type 1 DM, resolving diarrhea and associated fecal incontinence after 2 days of therapy Improved stool form, frequency, and urgency in RCT of 120 IBS-D patients