Hypoglycemia: workup and management
Glucose <70 mg/dL (level 1), <54 mg/dL (level 2), or any level with altered mental status needing assistance (level 3). Treat immediately, then find the cause. In people without diabetes, confirm Whipple's triad and draw a critical sample before treatment when possible.
Working diagnosis
Adult · US guidelines
Draft · awaiting physician review
01Orient
What's new in the evidence
- Endocrine Society 2023: CGM and hypoglycemia-aware regimens for people at high risk
- Ready-to-use glucagon (nasal 3 mg, autoinjector) for out-of-hospital rescue
- ADA 2026 standards: every hospital needs a nurse-initiated hypoglycemia protocol; revise the regimen after any glucose <70 mg/dL
Differential diagnoses
- Insulin or sulfonylurea in diabetes (dose, missed meal, renal decline)
- Sepsis (can't miss)
- Liver failure, alcohol
- Adrenal insufficiency (can't miss)
- Insulinoma, non-islet cell tumor
- Post-bariatric surgery hypoglycemia
- Factitious insulin or sulfonylurea use
02Assess
Risk scores and decision tools
- Level 1 (<70), level 2 (<54) and level 3 (severe, needs assistance)
- Whipple's triad for hypoglycemia without diabetes
- Critical sample: insulin, C-peptide, β-hydroxybutyrate, sulfonylurea screen
Key history questions
- Diabetes medication doses, timing, recent changes
- Food intake, alcohol
- Kidney or liver disease
- Prior episodes and awareness of symptoms
- Access to others' medications
Examination findings
- Mental status, sweating, tremor
- Focal neurological signs (can mimic stroke)
- Signs of sepsis, liver disease, adrenal insufficiency
03Investigate
Initial investigations
- Point-of-care glucose, confirmed with lab glucose
- BMP, LFTs
- Blood cultures if febrile
Advanced investigations
- Without diabetes: during hypoglycemia draw insulin, C-peptide, proinsulin, β-hydroxybutyrate and a sulfonylurea screen
- Morning cortisol or ACTH stimulation if adrenal insufficiency suspected
04Treat
Immediate management
- Awake and able to swallow: 15–20 g fast-acting glucose, recheck in 15 minutes
- Unable to take oral: dextrose IV (e.g., 25 g as D50, or D10 boluses)
- No IV access: glucagon 1 mg IM/SC or 3 mg intranasal
- Thiamine before glucose if malnourished or alcohol use disorder
First-line treatment
- Follow with a meal or a D10 infusion if hypoglycemia may recur
- Sulfonylurea-induced: admit, D10 infusion, octreotide 50–100 mcg SC every 6–8 hours
- Reduce or stop the causal medication; adjust for kidney function
Second-line treatment
- Long-acting insulin overdose: prolonged dextrose infusion and close monitoring
- Endocrinology workup for unexplained hypoglycemia without diabetes
Specialist referrals
- Diabetes team or endocrinology
- Toxicology or psychiatry for intentional overdose
05Disposition
Admission criteria
- Sulfonylurea or long-acting insulin cause
- Recurrent hypoglycemia, unclear cause, sepsis
- Intentional overdose
Safe discharge criteria
- Clear cause from short-acting insulin, fully recovered after eating
- Responsible adult present and medication plan adjusted
Follow-up timing
- Primary care or diabetes review within 1 week
Patient instructions
- Carry fast-acting glucose; household members know how to use glucagon
- Do not drive until glucose is stable; check before driving
Monitoring
- Glucose every 1 hour initially, longer for sulfonylureas
Clinical pearls and pitfalls
- Sulfonylurea hypoglycemia can recur for 24 hours or more; dextrose alone can provoke more insulin release
- Recurrent hypoglycemia impairs awareness; relax glycemic targets in older adults
RefGuidelines and landmark evidence
For education only. Typical adult starting points; confirm doses against renal function, allergies, interactions and your institution's protocols. Not a substitute for clinical judgment or senior review.