25 mg meals w/1st bite of. food, titrate Q 4 8 weeks; adjust based on 1 postprandial glucose; 100 mg TID max

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1 Table Selected Non-Insulin Antihyperglycemic Agents Class Drug (Brand) Dosing Comments -Glucosidase inhibitors Acarbose a (Precose) 25 mg meals w/1st bite of MOA: Enzyme inhibitor, delays hydrolysis of complex 25, 50, 100 mg tabs Miglitol (Glyset) 25, 50, 100 mg tabs food, titrate Q 4 8 weeks; adjust based on 1 postprandial glucose; 100 mg TID max carbohydrates % decrease in A 1C Contraindications: Renal dysfunction (Scr 2 mg/dl); inflammatory bowel disease; GI obstruction AEs: Flatulence, diarrhea, abdominal pain, may avoid through slow titration; acarbose ~14% have AST/ALT monitor Q 3 months Dosing requirements may decrease compliance Biguanide Metformin a (glucoph age, glucophage XL) IR 500 mg BID; increase by 500 mg Q week up to 2550 mg/day (850 mg Decrease hepatic glucose production and intestina glucose absorption; increases insulin sensitivity 500, 850, 1,000 mg tabs; 500, 750, 1,000 mg XR tabs TID) XR 500 1,000 mg/day max 2,500 mg/day; if not controlled with max dose, split BID 1 2% decrease in A 1C Contraindicated in renal dysfunction (Scr 1.5 mg/dl males, 1.4 mg/dl females); acute/chronic acidosis; discontinue in AKI or if patient to receive contrast (Reinitiate after 48 hours,

2 and normal serum creatinine concentrations are achieved.) Considered weight neutral typically causes weight loss AEs: Abdominal pain, cramping, flatulence; GI effects worse with IR vs. XR; take w/food and titrate slowly, B 12 deficiency Lactic acidosis (rare) Signs or symptoms of lactic acidosis include acidosis, nausea, vomiting, increased respiratory rate, abdominal pain, shock, and tachycardia. Precautions I. Age 80 years or older II. High risk of cardiovascular event or hypoxic state III. Hepatic impairment Congestive heart failure (especially if prone to exacerbations) Bile acid sequestrant Colesevelam (Welchol) 3.75 g/packet granules for suspension, 625 mg tabs Combination therapy: 3.75 g QD, g BID MOA: Unknown, may decrease glucose absorption and hepatic glucoseproduction and increase GLP % decrease in A 1C AEs: Constipation Separate from other meds binding may decrease absorption

3 Large tablet size/pill burden LDL decrease 15 19%; increases triglycerides D 2 agonist Bromocriptine(Cycl 0.8 mg QAM; titrate by 0.8 mg Q MOA: Unknown, believed to reset circadian rhythm oset) 0.8 mg tabs week up to 4.8 mg/day and reverse insulin resistance % decrease in A 1C Contraindicated with, agonists, azole antifungals; risk of serotonin syndrome with serotonergic agents; caution with psychiatric history Extensive hepatic metabolism AEs: Increased CNS effects including dizziness, HA, fatigue, drowsiness; hypotension, syncope; GI upset take with food DPP-IV inhibitors (Dipeptidyl peptidase-4 inhibitors) Linagliptin (Tradjenta) 5 mg tabs 5 mg QD; no renal adjustments MOA: Inhibits enzymeresponsible for metabolism of incretin hormones and increased [GLP-1], [GIP] % decrease in A 1C Saxagliptin (Onglyza) 2.5, 5 mg tabs mg QD; CrCl <50 ml/min: 2.5 mg QD AEs: Headache, peripheral edema, hemorrhagic pancreatitis

4 Sitagliptin (Januvia) 25, 50, 100 mg tabs 100 mg QD; CrCl ml/min: 50 mg QD; Weight neutral Linagliptin, saxagliptin CYP3A4 substrates; CrCl <30 ml/min: 25 mg QD decrease saxagliptin to 2.5 mg QD w/strong 3A4 inhibitor GLP-1 agonists Liraglutide (Victoza) 6 mg/ml soln; 3 ml 0.6 mg SQ QD x 1 week, then 1.2 mg SQ QD; may titrate to 1.8 mg QD MOA: GLP-1 analog, increases glucose-dependent insulin secretion, decreasesglucagon secretion, pen delays gastric emptying and increases satiety Exenatide (Byetta) 250 g/ml soln; 2.4 ml = 60 IR doses; (Bydureon) 2 mg soln = 1 XR dose IR 5 g BID within 60 min of meal; 10 g BID after 1 month if needed; XR 2 mg Q week CrCl <30 ml/min not recommended % decrease in A 1C ; % decrease in A 1C XR exenatide Weight loss Contraindications: Multiple endocrine neoplasia syndrome type 2; family history of medullary thyroid carcinoma AEs: N/V/D, dose-related, decreases with exposure, hemorrhagic pancreatitis, injection side irritation Meglitinides Nateglinide a (Starlix 120 mg TID MOA: Stimulates glucose-dependent insulin release ) 60, 120 mg tabs Repaglinide (Prandi n) 0.5, 1, 2 mg tabs Initial: 0.5 mg (untreated or A 1C <8%); 1 2 mg (prior treatment or A 1C >8%); max 4 mg/dose (16 mg/day) % decrease in A 1C Weight gain ( insulin secretion) CrCl ml/min: 0.5 Take within min of meal; skip dose if skip meal

5 mg/dose AEs: Hypoglycemia Nateglinide CYP 2C9/3A4 substrate; CI conivaptan Repaglinide CYP3A4/2C8 substrate; CI conivaptan; also metabolized via glucuronidation; CI gemfibrozil Sulfonylureas Glimepiride a (Amary l) 1, 2, 4 mg tabs 1 2 mg QAM with breakfast (or 1st meal); max 8 mg/day MOA: Stimulates pancreatic insulin release, decreases hepatic glucose production Glipizide a (Glucotrol ) 5, 10 mg tabs (Glucotrol XL) 2.5, 5, 10 mg XR tabs Glyburide a (DiaBeta) 1.25, 2.5, 5 mg tabs (Micronase) 1.5, 3, 6 mg micronized tabs IR 5 mg QD; 40 mg max; divide doses >15 mg XR 5 mg QD; 20 mg max CrCl <50 ml/min: decrease dose by 50% Regular tabs micronized tabs mg (1.5 3 mg micronized) initial; max 20 mg/day (12 mg/day micronized); max doses more effective if divided; 1 2% decrease in A 1C Weight gain ( insulin secretion) AE: Adverse effects i. Common: Hypoglycemia, weight gain ii. Less common: Rash, headache, nausea, vomiting, photosensitivity Contraindications/precautions I. Hypersensitivity to sulfonamides II. III. Patients with hypoglycemic unawareness Poor renal function (glipizide may be a better option than glyburide or glimepiride in impairment because drug or active metabolites are not renally eliminated) CrCl <50 ml/min not recc elderly patients or in those with Sulfonylureas associated w/increased CV mortality vs. diet/insulin

6 Caution in sulfonamide allergy, G6PD deficiency Glimepiride, glipizide CYP2C9 substrates, metabolites excreted in urine Secondary failure common with beta-cell destruction; pancreas unable to continue insulin production Thiazolidinediones Pioglitazone (Actos) 15, 30, 45 mg tabs mg QD; max 45 mg 4 mg QD; max 8 mg/day (better MOA: PPAR-gamma agonists; increases insulin sensitivity Rosiglitazone (Avan dia) 2, 4, 8 mg tabs results if divided) % decrease in A 1C Weight gain Fluid retention (particularly peripheral edema), worse with insulin use (manufacturer of rosiglitazone states to no longer use with insulin). Edema less responsive to diuretic therapy AEs: Edema (up to 15%), HF, HA, increases fracture risk (rosi >> pio) Pioglitazone: Increased risk of bladder cancer Rosiglitazone: Increased risk of MI Increased HDL (rosi and pio): Increased LDL (rosi)

7 Contraindications/precautions Hepatic impairment Class III/IV heart failure Existing fluid retention Amylinomimetic Pramlintide (Symlin, DM1 15 g SQ just prior to meals; MOA: Amylin analog; delays gastric emptying, SymlinPen 60, SymlinPen 120) titrate Q 3 days (if nausea tolerable) target g centrally mediated appetite suppression, decreasesglucagon secretion 1,000 g/ml; 1.5 ml (60 pen), 2.7 ml (120 pen) injectors DM2 15 g SQ just prior to meals; titrate Q 3 days (ifnausea tolerable) target g % decrease in A 1C Weight loss (secondary to decreased intake) Decrease insulin 50% at initiation to mitigate risk of hypoglycemia AEs: Severe hypoglycemia, N/V, gastroparesis, HA, Contraindications: Gastroparesis, hypoglycemic unawareness (caution w/beta blockers secondary to masking hypoglycemic symptoms) Ahmed A AlAmer PharmD : reference :- Pharmacotherapy Bedside Guide,Therapeutics updates

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