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.

 

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