What can be given to an inpatient with diarrhea instead of metformin (biguanide)?

Alternative Medications for Inpatients with Metformin-Induced Diarrhea

For inpatients experiencing diarrhea from metformin, a DPP-4 inhibitor such as linagliptin is the most appropriate alternative medication due to its minimal gastrointestinal side effects, lack of hypoglycemia risk, and ability to be used in patients with renal impairment.

Understanding Metformin-Induced Diarrhea

Metformin is a first-line medication for type 2 diabetes that commonly causes gastrointestinal side effects, including diarrhea. These side effects can occur:

• At initiation of therapy
• After dose increases
• Or even after years of stable therapy 1, 2

Metformin-induced diarrhea occurs due to:

• Alteration in gut microbiota
• Increased intestinal glucose
• Enhanced ileal bile salt reabsorption 2

Alternative Medication Options

First-Line Alternatives

1. DPP-4 Inhibitors

   • Linagliptin: Preferred option for inpatients with renal impairment 3
   • Other options: Sitagliptin, saxagliptin, alogliptin
   • Advantages: Few side effects, minimal risk of hypoglycemia
   • Considerations: Higher cost may be a barrier for some patients 3

2. Sulfonylureas (Short-Acting)

   • Glipizide: Preferred over longer-acting sulfonylureas
   • Caution: Monitor for hypoglycemia
   • Avoid: Glyburide (longer-acting) in older adults 3
   • Drug interactions: Many antimicrobials (fluoroquinolones, sulfamethoxazole-trimethoprim) can increase hypoglycemia risk 3

Other Options to Consider

1. Extended-Release Metformin

   • May be better tolerated than immediate-release formulation
   • Studies show significantly fewer GI side effects when patients are switched from immediate-release to extended-release metformin 4, 5
   • In one study, diarrhea frequency decreased from 18.05% to 8.29% after switching 5

2. SGLT2 Inhibitors

   • Options include empagliflozin, dapagliflozin, canagliflozin
   • Not ideal for acute inpatient setting due to risk of euglycemic DKA and genital infections

3. Insulin Therapy

   • Appropriate for inpatient glycemic control
   • Can be used temporarily until outpatient regimen is established
   • No GI side effects

Decision Algorithm for Inpatients

1. Assess severity of diarrhea:

   • If mild: Consider extended-release metformin
   • If moderate to severe: Discontinue metformin completely

2. Evaluate renal function:

   • eGFR ≥30 mL/min/1.73m²: Any alternative is appropriate
   • eGFR <30 mL/min/1.73m²: Linagliptin or insulin are preferred options

3. Consider hypoglycemia risk:

   • High risk (elderly, inconsistent oral intake): Avoid sulfonylureas
   • Low risk: Any alternative is appropriate

4. Duration of inpatient stay:

   • Short stay: Temporary insulin with outpatient follow-up
   • Longer stay: Oral agent like DPP-4 inhibitor

Practical Considerations

• Monitoring: Assess resolution of diarrhea after metformin discontinuation
• Patient education: Explain the connection between metformin and diarrhea symptoms
• Documentation: Note metformin intolerance in discharge summary to prevent restarting
• Follow-up: Arrange outpatient follow-up to assess the effectiveness of the alternative medication

Common Pitfalls to Avoid

1. Misdiagnosis: Metformin-induced diarrhea is often misdiagnosed as irritable bowel syndrome or other GI disorders 2
2. Unnecessary testing: Consider a drug-free interval before ordering expensive diagnostic tests 1
3. Inadequate follow-up: Ensure clear communication with outpatient providers about metformin intolerance
4. Restarting metformin: Avoid restarting immediate-release metformin if patient had significant diarrhea

By selecting an appropriate alternative to metformin, inpatients experiencing diarrhea can maintain glycemic control while improving their gastrointestinal symptoms and overall quality of life.