Non-Insulin Meds for DM2
First Line – Start with this.
- Biguanide (Metformin)
- MOA: inhibits gluconeogenesis
- Weight loss, decreased mortality, decreased CV events. Because of this, continue even when insulin-dependent.
- AE: GI. Take with meals.
- CI in men with Cr >1.5 or women with Cr >1.4, or GFR<30.
- Cheapest ($4/month)
Second Line – Add to Metformin if no improvement in A1C in 3 months. Can add up to two second-line meds before starting insulin. In no particular order.
- Sulfonylureas – Glimiperide, Glipizide, Glyburide
- MOA: Stimulates B cells to release insulin
- AE: hpoglycemia, weight gain
- Decreases in effectiveness as pancreas worsens.
- cheap ($10/month)
- not preferable as monotherapy
- DPP4 Inhibitors – Saxagliptin, Sitagliptin (Januvia)
- MOA: Inhibits the inactivation of incretin –> increases incretin –> enhances insulin release.
- Low risk of hypoglycemia, weight neutral
- AE: Pancreatitis
- Less potent, more expensive
- Thiazolidinediones – Pioglitazone (Actos), Rosiglitazone
- MOA: PPARγ agonist –> increases GLUT4, increases insulin sensitivity.
- Weight gain, edema
- CI in CHF (cause cause fluid retention), bladder CA (particularly pioglitazone)
- Avoid in women with osteoporosis
- GLP-1 Receptor Agonist – Exenatide (Byetta)
- MOA: incretin mimetic –> enhances insulin release.
- CI in Gastroparesis, CrCl <30, MEN2, Medullary Thyroid Cancer
- Injection, not oral
Others – Not as well tolerated, minimally effective, expensive, and not in ADA treatment algorithm.
- α-Glucosidase inhibitor – Acarbose, Miglitol – inhibit breakdown of carbs
- Meglitinides – Nateglinide, Repaglinide
- Bile Acid Sequestrants – Colesevelam
- Dopamine Agonist – Bromocriptine
- Amyline Analogue – Pramlintide – treats both DM1 and 2. Injection, not oral
- Sodium-Glucose Cotransporter 2 Inhibitor (SGLT2 Inhibitors) – Canagliflozin, Dapagliflozin, Empagliflozin – newest drugs. INcrease urine glucose excretion. Because you get sugary urine, fungus and bacteria more likely to grow, and you can get yeast infections and UTIs, even in men.