What are the principles of blood sugar control in hospitalized patients taking oral medications, including those with diabetes and impaired renal function?

Blood Sugar Control in Hospitalized Patients Taking Oral Medications

Insulin is the preferred treatment for hyperglycemia in hospitalized patients, but oral medications can be continued selectively in stable, non-critically ill patients with mild-to-moderate hyperglycemia and adequate renal function. 1

Target Glucose Ranges

• Maintain blood glucose between 140-180 mg/dL (7.8-10.0 mmol/L) for most hospitalized patients to optimize outcomes while minimizing hypoglycemia risk 1, 2
• Initiate insulin therapy when glucose persistently exceeds 180 mg/dL on two separate measurements 2
• More stringent targets of 110-140 mg/dL may be appropriate for select stable patients who can achieve this without significant hypoglycemia, but aggressive targets below 110 mg/dL increase mortality and should be avoided 1

Glucose Monitoring Protocol

• For patients eating meals: Check blood glucose before each meal 1, 2
• For patients NPO (nothing by mouth): Monitor every 4-6 hours 1, 2
• For patients on IV insulin: Monitor every 30 minutes to 2 hours 1, 2

Decision Algorithm for Oral Medications vs. Insulin

When to Continue Oral Medications

Oral antidiabetic agents may be continued in hospitalized patients who meet ALL of the following criteria: 1

• Non-critically ill status (not in ICU)
• Mild-to-moderate hyperglycemia (glucose <250 mg/dL)
• Stable clinical condition with consistent oral intake
• Adequate renal function (see specific requirements below)
• No contraindications to specific agents

When to Switch to Insulin

Transition to insulin is mandatory for: 1, 2

• All critically ill patients requiring ICU care
• Patients with severe hyperglycemia (>250-300 mg/dL)
• Patients with inconsistent or no oral intake
• Patients with acute kidney injury or significant renal impairment
• Patients at risk for lactic acidosis (sepsis, hypoxia, shock)

Specific Oral Medication Considerations

Metformin - Critical Renal and Safety Parameters

Metformin must be discontinued in hospitalized patients with: 1, 3

• eGFR <30 mL/min/1.73 m² (absolute contraindication)
• eGFR 30-45 mL/min/1.73 m² (requires dose reduction or discontinuation)
• Risk factors for lactic acidosis: sepsis, hypoxia, shock, acute heart failure, liver failure
• Planned iodinated contrast procedures in patients with eGFR <60 mL/min/1.73 m²

Recent evidence from COVID-19 patients showed metformin increased lactic acidosis risk 4.46-fold in hospitalized patients, particularly with higher doses, worse kidney function, and severe illness. 1 This underscores the importance of measuring lactate levels in fragile patients and discontinuing metformin promptly if elevated.

Sulfonylureas - High Hypoglycemia Risk

Sulfonylureas should be discontinued in hospitalized patients due to: 1

• Sustained hypoglycemia risk, especially with inconsistent oral intake
• Increased risk in elderly patients, those on concurrent insulin, and patients with renal impairment
• Professional societies recommend against their use except potentially for glucocorticoid-induced hyperglycemia 1

Other Oral Agents

• Thiazolidinediones: Avoid due to fluid retention risk and delayed onset of action 1
• DPP-4 inhibitors and GLP-1 receptor agonists: Emerging evidence suggests potential safety in select patients, but insulin remains preferred 1

Insulin Regimens for Non-Critical Patients

For Patients with Good Oral Intake

Use basal-bolus-correction insulin regimen: 1, 2

• Basal insulin: Long-acting analog (glargine or detemir) once daily
• Prandial insulin: Rapid-acting analog (lispro, aspart, or glulisine) before each meal
• Correction insulin: Rapid-acting analog for glucose elevations

For Patients with Poor or No Oral Intake

Use basal insulin plus correction doses: 1, 2

• Basal insulin to prevent gluconeogenesis and ketogenesis
• Correction doses of rapid-acting insulin as needed
• Avoid prandial insulin if not eating

Critical Pitfall to Avoid

Never use sliding-scale insulin alone - this approach is ineffective, potentially dangerous, and strongly discouraged by all major guidelines because it lacks basal insulin coverage. 1, 2, 4

Protocol for Resuming Oral Medications Before Discharge

For patients whose oral medications were held during hospitalization: 1, 2

• Resume oral agents 1-2 days before discharge to assess glycemic response while still in hospital
• This allows observation for adverse effects and dose adjustments before the patient leaves

Discharge Planning Based on HbA1c

Measure HbA1c at admission to guide discharge planning: 2, 5, 6

• HbA1c <8%: Resume previous oral medications; follow-up with primary physician in 1 month 6
• HbA1c 8-9%: Continue basal insulin at home with protocol for dose adjustment; arrange diabetologist consultation 6
• HbA1c >9%: Discharge on basal-bolus insulin regimen OR previous oral agents plus 80% of hospital basal insulin dose; diabetologist consultation before discharge 2, 6

Hypoglycemia Prevention Protocol

Every hospital must implement a standardized hypoglycemia protocol: 1, 2

• Nurse-initiated treatment for glucose <70 mg/dL (3.9 mmol/L)
• Review insulin regimen after any glucose reading <70 mg/dL
• Document and track all hypoglycemic episodes for quality improvement 1

Common preventable causes of hypoglycemia to monitor: 1

• Nutrition-insulin mismatch (unexpected interruption of meals or tube feeds)
• Acute kidney injury (decreased insulin clearance)
• Inappropriate insulin dosing after first hypoglycemic episode
• Reduction in corticosteroid dose without insulin adjustment

Special Considerations for Renal Impairment

Patients with renal dysfunction require: 1, 3

• Lower insulin doses due to decreased clearance
• Avoidance of metformin (eGFR <30 mL/min) or dose reduction (eGFR 30-45 mL/min)
• More frequent glucose monitoring
• Heightened awareness of hypoglycemia risk

Renal clearance of metformin is approximately 3.5 times greater than creatinine clearance, with tubular secretion as the major elimination route. 3 In renal impairment, plasma half-life is prolonged and clearance decreased, substantially increasing lactic acidosis risk.

Drug Interactions Requiring Attention

Cationic drugs that reduce metformin clearance (OCT2/MATE inhibitors): 3

• Cimetidine, ranolazine, vandetanib, dolutegravir
• These increase metformin exposure and lactic acidosis risk

Carbonic anhydrase inhibitors increase lactic acidosis risk: 3

• Topiramate, zonisamide, acetazolamide, dichlorphenamide
• Consider more frequent monitoring if used with metformin

Alcohol potentiates metformin's effect on lactate metabolism - warn patients against excessive intake 3

Consultation Recommendations

Consult specialized diabetes or glucose management team when available for all hospitalized patients with diabetes to optimize outcomes and reduce complications. 1