Oral Diabetes Drugs: Metformin vs Sulfonylureas vs SGLT2 vs GLP-1 — MOA, Hypo Risk, Key Warnings
Four drug classes, four completely different risk profiles. Pick the wrong one on NCLEX and you'll miss that only sulfonylureas cause true hypoglycemia, only metformin demands a contrast-dye hold, and SGLT2 inhibitors can trigger DKA even with normal glucose. Each class has a signature danger — mix them up and you'll choose the wrong teaching point.
Comparison
- Biguanide: ↓ hepatic glucose, ↑ insulin sensitivity
- ↑ pancreatic insulin secretion
- ↑ urinary glucose excretion
- Incretin: glucose-dependent insulin, ↓ glucagon
- First-line T2DM
- T2DM, glipizide & glyburide
- T2DM with CV or renal benefit
- T2DM, semaglutide & liraglutide
- PO
- PO
- PO, the "-flozins"
- ★SubQ injection — not oral
- Renal function (eGFR) before dosing
- Hypoglycemia signs
- Volume status, genital/UTI symptoms
- GI tolerance, nausea & vomiting
- Monitor A1c & blood glucose
- Monitor A1c & blood glucose
- Monitor A1c & blood glucose
- Monitor A1c & blood glucose
- GI upset, B12 deficiency
- ★No hypoglycemia alone, weight-neutral
- ★HYPOglycemia + weight gain
- Genital/UTI infections, volume depletion
- Nausea/vomiting, weight loss
- ★Lactic acidosis — hold for IV contrast
- Severe hypoglycemia, esp. glyburide
- ★Euglycemic DKA — ketones despite normal BG
- Thyroid C-cell tumor risk (black box)
- Hold if eGFR <30 or IV contrast
- Sulfa allergy; caution in elderly
- Recurrent genital infection, hypovolemia
- Personal/family medullary thyroid CA, MEN2
- Take with food to ↓ GI upset
- Take with meals
- Carry fast sugar for lows
- Hydrate; perineal hygiene to prevent infection
- Rotate SubQ sites; expect early nausea
Metformin
- Biguanide: ↓ hepatic glucose, ↑ insulin sensitivity
Sulfonylureas
- ↑ pancreatic insulin secretion
Metformin
- First-line T2DM
Sulfonylureas
- T2DM, glipizide & glyburide
Metformin
- PO
Sulfonylureas
- PO
Metformin
- Renal function (eGFR) before dosing
Sulfonylureas
- Hypoglycemia signs
Metformin
- Monitor A1c & blood glucose
Sulfonylureas
- Monitor A1c & blood glucose
Metformin
- GI upset, B12 deficiency
- ★No hypoglycemia alone, weight-neutral
Sulfonylureas
- ★HYPOglycemia + weight gain
Metformin
- ★Lactic acidosis — hold for IV contrast
Sulfonylureas
- Severe hypoglycemia, esp. glyburide
Metformin
- Hold if eGFR <30 or IV contrast
Sulfonylureas
- Sulfa allergy; caution in elderly
Metformin
- Take with food to ↓ GI upset
Sulfonylureas
- Take with meals
- Carry fast sugar for lows
★ marks the fact that sets a column apart.
Clinical Pearl
Sulfonylureas cause hypo, metformin demands a contrast hold, SGLT2 causes UTI + euglycemic DKA — match the danger to the drug.
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