Non-Insulin Medications for T2D

GLP-1 and GIP agonists (lowers A1C 0.5-1.5%)

Liraglutide (Victoza): Daily (max 1.8 mg)

• Saxenda for weight loss.

Dulaglutide (Trulicity): SC weekly (max 4.5 mg)

Semaglutide (Ozempic): SC weekly (max 2 mg) or PO daily (max 14 mg)

• Wegovy for weight loss.

Exenatide: SC BID (max 10 mcg BID) *not for CrCl < 30

Twincretin - Tirzepatide (Mounjaro): SC weekly (max 15 mg)

• Zepbound for weight loss.

Boxed Warning: All (except exenatide) have a risk of thyroid C-cell carcinoma.

Warnings: pancreatitis, caution with severe GI distresses (including gastroparesis), increased risk of pulmonary aspiration

SE: weight loss, N/V/D, hygoglycemia

Notes:

• Exenatide is on NIOSH list.

• Admin: Give dose within 60 min before meals (exenatide) and > 30 min before first food/drink (rybelsus).

SGLT-2 Inhibitors (lowers A1C 0.7-1%)

Dapagliflozin (Farxiga): 5 mg daily AM (max 10 mg)

Empagliflozin (Jardiance): 10 mg daily AM (max 25 mg)

Canagliflozin (Invokana): 100 mg daily before 1st meal (especially if CrCl 30-59 but max 300 mg)

Warnings: ketoacidosis (can occur w/ BG < 250), genital mycotic infections, UTI, necrotizing fasciitis of the perineum, higher risk of amputation and fractures (cana + bexa)

SE: increased urination, thirst, Mg/PO4, K+ (hyperkalemia concern with cana)

Notes:

• Recommended generally if eGFR > 20 mL/min.

• Not recommended for pts in dialysis.

Biguanide (lowers A1C 1-2%)

Metformin

Dosing: Titrate weekly to usual maintenance dose of 1,000 mg BID (max 2,000-2,550 mg/day)

• IR: 500 mg daily or BID

• ER: 500-1000 mg daily

  • ghost tablet

• Give w/ meal to lower GI upset.

Boxed Warning: lactic acidosis w/ renal impairment, contrast dye, alcohol, and hypoxia

CI: eGFR < 30 and metabolic acidosis (including DKA)

Warnings: Don’t start if eGFR 30-45 and vitamin B12 deficiency.

SE: GI effects

Notes: weight neutral and no hypoglycemia

Sulfonylureas (lowers A1C 1-2%)

CI: Sulfa allergy, T1D, DKA

Warnings: Hypoglycemia - Avoid in older adults.

SE: weight gain, nausea

Notes:

• Glipizide IR - 30 min before meals

  • Others are taken w/ first meal of the day. Hold doses if NPO.

• Glucotrol XL: ghost tablet

Meglitinides (lowers A1C 0.5-1.5%)

Warnings: Hypoglycemia

SE: weight gain, upper respiratory tract infections

Notes:

• Skip dose if meal was skipped.

• Repaglinide - 30 min before meals.

• Nateglinide - 1-30 min before meals.

DPP-4 Inhibitors

Warnings: pancreatitis, severe arthralgia, bullous pemphigoid

• Saxa- and alogliptin: risk of HF

  • Careful w/ CYP3A4 inducers.

• Alogliptin: hepatotoxicity

SE: nasopharyngitis, URTIs, HA, rash

Notes:

• Linagliptin (Tradjenta) doesn’t need renal dose adjustment.

• Weight neutral, low hypoglycemia risk

Thiazolidinediones

Boxed Warning: Cause/exacerbate HF so avoid w/ NYHA Class III/IV HF.

Warnings: edema, fracture risk, ovulation stimulation (concern: unintended pregnancy), bladder cancer risk

SE: peripheral edema, weight gain, URTIs, myalgia