Oral hypoglycemics Jennifer R Marks, MD

Oral hypoglycemics Factors to consider: Cost Availability Side effects Tolerability Risk Accessory benefits

metformin Metformin is the preferred initial pharmacologic agent for the treatment of type 2 diabetes. A Once initiated, metformin should be continued as long as it is tolerated and not contraindicated; other agents, including insulin, should be added to metformin. A Long-term use of metformin may be associated with biochemical vitamin B12 deficiency, and periodic measurement of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy. B https://clinical.diabetesjournals.org/content/37/1/11

SGLT-2 inhibitors

Canagliflozin (Invokana) Dapagliflozin (Farxiga) SGLT-2 inhibitors Canagliflozin (Invokana) 100 or 300mg daily with breakfast Dapagliflozin (Farxiga) 5 or 10 mg daily q AM Empagliflozin (Jardiance) 10 or 25 mg daily q AM PDR.net

SGLT-2 inhibitors Among patients with type 2 diabetes who have established ASCVD, sodium–glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide 1 (GLP-1) receptor agonists with demonstrated CVD benefit are recommended as part of the antihyperglycemic regimen. A Among patients with ASCVD at high risk of heart failure or in whom heart failure coexists, SGLT2 inhibitors are preferred. C For patients with type 2 diabetes and CKD, consider use of an SGLT2 inhibitor or GLP-1 receptor agonist shown to reduce risk of DKD progression, cardiovascular events, or both. C https://clinical.diabetesjournals.org/content/37/1/11

SGLT-2 inhibitors Renally dose adjust Increased risk amputation & fracture (canagliflozin) DKA risk GU infection including Fournier’s gangrene

GLP-1 RAs

GLP-1 RAs Dulaglutide (Trulicity) Exenatide (Byetta) weekly Exenatide (Byetta) twice daily Exenatide extended release (Bydureon) Liraglutide (Victoza) daily Lixisenatide (Adlyxin) Semaglutide (Ozempic)

GLP-1 RAs Among patients with type 2 diabetes who have established ASCVD, sodium–glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide 1 (GLP-1) receptor agonists with demonstrated CVD benefit are recommended as part of the antihyperglycemic regimen. A For patients with type 2 diabetes and CKD, consider use of an SGLT2 inhibitor or GLP-1 receptor agonist shown to reduce risk of DKD progression, cardiovascular events, or both. C In most patients who need the greater glucose-lowering effect of an injectable medication, GLP-1 receptor agonists are preferred to insulin. B

GLP-1 RAs Please note that this class is NOT actually orally administered but SQ; they get lumped together with orals since they are non-insulin products Liraglutide has best evidence for CV benefit Risk of thyroid tumors GI upset is common

DDP-4 inhibitors

DDP-4 inhibitors Sitagliptin (Januvia) Saxagliptin (Onglyza) 25, 50, or 100mg once daily Saxagliptin (Onglyza) 2.5 or 5mg once daily Linagliptin (Trajenta) 5mg once daily Alogliptin (Nesina) 6.25, 12.5, or 25mg once daily

DDP-4 inhibitors Renally dose adjust Risk of pancreatitis

Rosiglitazone (Avandia) Thiazolidinediones Rosiglitazone (Avandia) 2, 4, or 8mg daily or divided BID Pioglitazone (Actos) 15, 30, or 45mg once daily

Thiazolidinediones Weight gain CHF/fluid retention Risk of Fracture Risk of bladder cancer

sulfonylureas Glyburide (DiaBeta, Glynase, or Micronase)  1.25, 1.5, 2.5, 3, 5, 6 up to 20mg once daily with breakfast or in divided doses Glimepiride (Amaryl) 1, 2, or 4mg up to 8mg once daily with breakfast Glipizide (Glucotrol) 5 or 10mg up to 20mg BID with meals Also comes in XL form (not on LAC+USC formulary) Chlorpropamide (Diabinese)

sulfonylureas Risk of hypoglycemia Weight gain In CKD, avoid glyburide (longest half-life) & use caution with others

Oral hypoglycemics Consider initiating dual therapy in patients with newly diagnosed type 2 diabetes who have A1C ≥1.5% (12.5 mmol/mol) above their glycemic target. E

ABIM-style question Patient is a 64 yo female who has NIDDM, htn, hld, CKD. She has recently been discharged from the hospital after a STEMI complicated by CHF with an EF of 35% as well as an AKI. She currently feels well, has no angina, and is eulovemic. PE is normal (except BMI of 38) including BP 122/68, pulse 68, no JVD, RRR with no gallop, CTA bilat, no edema. Her only DM medication is MTF 500 mg BID.

You review her recent labs drawn several days ago prior to the office visit: HgbA1c 8.9 Sodium 138 Potassium 4.8 Chloride 111 CO2 19 Glucose 198 Calcium 9.8 BUN 21 Creatinine 1.66 (baseline 1.35; max1.88 with recent AKI) GFR 45 LFTs nl WBC 7.6 RBC 3 Hgb 12 Hct 36 MCV 88 RDW 14 Platelets 299 TSH 2.43

ABIM-style question Which of the following would you advise the patient in terms of managing her DM? A) Her metformin 500mg BID must be stopped B) Initiating canagliflozin may benefit her CV and renal status but must be renally dose adjusted C) Exenatide should not be offered since it will cause weight gain D) A, B, & C E) B & C

ABIM-style question Which of the following would you advise the patient in terms of managing her DM? A) Her metformin 500mg BID must be stopped B) Initiating canagliflozin may benefit her CV and renal status but must be dose adjusted C) Exenatide should not be offered since it will cause weight gain D) A, B, & C E) B & C max dose 100 mg daily & monitor renal function closely

Additional references https://www.nejm.org/doi/pdf/10.1056/NEJMoa1603827 https://www-nejm-org.libproxy1.usc.edu/doi/pdf/10.1056/NEJMoa1504720