Which diabetes medications should be withheld in hospitalized patients?

Diabetes Medications to Withhold in Hospitalized Patients

Insulin is the preferred treatment for most hospitalized patients with diabetes, and the majority of oral diabetes medications should be discontinued due to safety concerns, inflexibility in dosing, and inability to respond to rapidly changing clinical conditions. 1

Medications That Should Be Withheld

Metformin - HIGHEST PRIORITY TO DISCONTINUE

Metformin should be avoided in most hospitalized patients due to the significantly elevated risk of lactic acidosis in the hospital setting. 1, 2

Key reasons for discontinuation:

• Risk of lactic acidosis increases dramatically when hospitalized patients develop hypoxia, hypoperfusion, renal insufficiency, cardiac disease (including CHF), or severe infection—all of which are common in the inpatient setting 1, 2
• COVID-19 infection increases lactic acidosis risk 4.46-fold in metformin users 2, 3
• Absolute contraindication when eGFR <30 mL/min/1.73 m² 1, 2
• Must be discontinued in patients with sepsis, shock, acute kidney injury, severe illness, or tissue hypoxia 2, 3

SGLT2 Inhibitors (e.g., canagliflozin, empagliflozin, dapagliflozin)

SGLT2 inhibitors are not recommended for routine in-hospital use and should be avoided in severe illness. 1

Specific contraindications:

• Severe illness, ketonemia, or ketonuria 1
• Prolonged fasting and surgical procedures 1
• Must be stopped 3 days before scheduled surgeries (4 days for ertugliflozin) per FDA warning 1
• Markedly increased risk of diabetic ketoacidosis, particularly in type 1 diabetes but also reported in type 2 diabetes 4

Sulfonylureas (e.g., glyburide, glipizide, glimepiride)

Sulfonylureas should not be used routinely in hospitalized patients due to high hypoglycemia risk. 1, 3

Problems with inpatient use:

• Long duration of action predisposes to prolonged, potentially life-threatening hypoglycemia 1, 3
• Particularly dangerous in patients with reduced oral intake, which is common during hospitalization 1
• Cannot be titrated rapidly to match changing insulin requirements 1

Meglitinides (repaglinide, nateglinide)

Meglitinides should be avoided due to lack of clinical trial data in hospitalized patients and their primarily prandial effect. 1

• No evidence supporting safety or efficacy in the hospital setting 1
• Primarily effective for postprandial glucose, offering limited benefit in patients with variable oral intake 1

Thiazolidinediones/TZDs (pioglitazone, rosiglitazone)

TZDs are not suitable for hospital use due to delayed onset of action and fluid retention. 1

Specific concerns:

• Delayed onset of effect (weeks) makes them inappropriate for acute glycemic management 1
• Increase intravascular volume, problematic in patients with CHF or hemodynamic instability 1
• Particular concern in patients with acute coronary ischemia or undergoing interventions 1

GLP-1 Receptor Agonists (exenatide, liraglutide) and Pramlintide

These agents are not appropriate for most hospitalized patients, particularly those who are NPO or have reduced caloric intake. 1

Limitations:

• Work mainly by reducing postprandial hyperglycemia, ineffective in NPO patients 1
• Propensity to induce nausea initially makes initiation problematic with altered food intake 1
• Limited flexibility for dose titration in acute settings 1

DPP-4 Inhibitors (sitagliptin, saxagliptin, alogliptin)

While no specific safety concerns exist, DPP-4 inhibitors have limited utility in hospitalized patients. 1

• FDA bulletin warns to consider discontinuing saxagliptin and alogliptin in patients who develop heart failure 1
• Mainly effective on postprandial glucose, limited effect in NPO patients 1
• Limited experience and no published data in hospital settings 1

Why Insulin is Preferred

Insulin provides the flexibility, rapid titration capability, and safety profile needed in the hospital setting. 1

• Can be adjusted rapidly to match changing clinical conditions 1
• Effective regardless of oral intake status 1
• Basal-bolus regimens achieve glycemic control (mean glucose <140 mg/dL) in 68% of patients 1
• No contraindications related to renal or hepatic function (though doses may need adjustment) 1

Critical Clinical Pitfalls to Avoid

• Never continue metformin in patients with sepsis, acute kidney injury, or severe illness—the risk of fatal lactic acidosis outweighs any glycemic benefit 1, 2, 3
• Do not use sliding-scale insulin as monotherapy—it is ineffective and leads to poor glycemic control 1
• Avoid premixed insulin formulations in the hospital due to significantly increased hypoglycemia risk compared to basal-bolus therapy 1
• Stop SGLT2 inhibitors at least 3 days before any scheduled surgery to prevent ketoacidosis 1

When Restarting Oral Agents After Discharge

• Metformin can only be restarted if eGFR >30 mL/min/1.73 m² and all acute illness has resolved 2, 3
• Reassess kidney function before restarting metformin 2
• Consider dose reduction if eGFR 30-45 mL/min/1.73 m² 2