Non-Insulin Diabetes Medications
ADA Standards of Care 2025
Updated: choose by the patient's other conditions
For type 2 diabetes with heart disease, heart failure, or chronic kidney disease, an SGLT2 inhibitor and/or GLP-1 receptor agonist with proven benefit is recommended regardless of A1C or metformin use. For weight management, GLP-1 RAs or tirzepatide are preferred. Older guides that only list metformin, sulfonylureas and insulin are out of date.
| Class | Examples | Key points |
|---|---|---|
| Biguanide | metformin | First-line for many. ↓ liver glucose output. No hypoglycemia alone. GI upset (take with meals; ER form helps); B12 deficiency. Not if eGFR <30. Hold around iodinated contrast in kidney impairment or unstable patients; restart after 48 h if kidney function is stable. Rare lactic acidosis. |
| SGLT2 inhibitors (-gliflozin) | empagliflozin, dapagliflozin, canagliflozin | Glucose leaves in urine. Protect heart and kidneys. Genital yeast infections, UTIs, dehydration, low BP, euglycemic DKA (DKA with near-normal glucose). Hold ~3 days before surgery and when acutely ill or not eating. |
| GLP-1 receptor agonists | semaglutide (injection or tablet), dulaglutide, liraglutide; tirzepatide (GIP/GLP-1) | Weekly or daily injection. Weight loss; heart benefit. Nausea, vomiting, diarrhea; pancreatitis (severe abdominal pain → stop, report); gallbladder disease. Slow stomach emptying: tell the anesthesia team (aspiration risk). Not with personal or family history of medullary thyroid cancer or MEN2. Oral semaglutide: empty stomach, ≤4 oz water, wait 30 min. |
| DPP-4 inhibitors (-gliptin) | sitagliptin, linagliptin | Modest effect; weight-neutral; low hypoglycemia. Joint pain, pancreatitis. Don't combine with a GLP-1 RA. |
| Sulfonylureas | glipizide, glimepiride, glyburide | Force insulin release: hypoglycemia (especially older adults: avoid glyburide), weight gain. Take with breakfast; don't skip meals. |
| Thiazolidinediones (-glitazone) | pioglitazone | Fluid retention, heart failure (avoid in HF), weight gain, fractures. Monitor liver tests. |
| Alpha-glucosidase inhibitors | acarbose | Take with the first bite; gas, bloating. Treat lows with glucose (table sugar won't be absorbed well). |
Targets (individualized)
| A1C | <7% for many adults (less strict, e.g. <8%, for frail or older adults) |
| Before meals | 80–130 mg/dL |
| 1–2 h after meals | <180 mg/dL |
| Hypoglycemia | Level 1 <70 · Level 2 <54 · Level 3: needs help from another person |
Nursing points
- Before contrast scans: check metformin and kidney function.
- Before surgery: ask about SGLT2 inhibitors and GLP-1 RAs (both may need holding per protocol).
- Teach foot care, eye exams yearly, kidney checks (urine albumin), BP and cholesterol control.
- Watch for hypoglycemia when combining sulfonylureas or insulin with other agents.
Memory hook
-gliflozin → glucose flows out in urine (think infections and fluid loss). -gliptin → gentle "tip" of glucose control. -glutide → glut-ted feeling: full stomach, nausea, weight loss.