Endocrinology

Get here fast: phcnotes.com/endo

 

Alpha-Glucosidase Inhibitors

acarbose=Glucobay: IND: T2DM. MOA: Delays/prevents digestion of complex carbs by inhibiting alpha-glucosidases. EVD: Lowers A1C 0.4-0.9% (relatively small effect). Max effect in ~8w. ADM: T w/ first bite of meal. AE: abdominal pain21%, Diar33%, flatulence71%. CI: IBD/IBS, past bowel obstruction. MON: LFT q3 months for 1y DOS: Start=25mg once/d. Maint=50-100mg TID. OTH: No hypoglycemia or weight gain. Tx hypoglycemia w/ glucose not sucrose.
miglitol: Not avail in Can.

 

Antithyroid

methimazole=Tapazole: IND: Hyperthyroidism. EVD: Improvement in 1-3 weeks. AE: Rash, upset stomach, heartburn, joint pain.

 

Biguanides

metformin=Glucophage=Glumetza: AVL: PO. IND: T2DM. MOA: Increases insulin sensitivity, decreases glucose production in liver, increases glucose uptake in muscle and fat, and decreases glucose absorption in small intestine. EVD: Reduces A1C by 1-1.5%. ADM: T w/ food to decrease stomach upset. AE: Diar, Naus, anorexia, metallic taste, lactic acidosisrare, anemia, photosensitivity, B12 malabsorption. CI: >80yo, CrCl<30, alcoholism, liver failure, severe CV/pulmonary disease. AUX: T w/ food. DOS: Start=500mg once/d. Max=1000mg BID. OTH: Can improve ovulation in Polycystic Ovarian Syndrome.

 

Combination Antidiabetics

Soliqua=insulin glargine100U/mL + lixisenatide33μg/mL AVL: SubQ (3mL prefilled disposable pen). IND: adults w/ T2DM inadequately controlled on basal insulin alone or in combination w/ metformin. ADM: Once/d within 1hr of first meal. Inject SubQ in abdomen, deltoid or thigh. DOS: Once/d injection. 1U of Soliqua=1U insulin glargine and 0.33μg of lixisenatide. Dose must be individualized. Max=60U/d. Not intended for pts who require <15 or >60U basal insulin/d. OTH:
Steglujan=ertugliflozin + sitagliptin: AVL: PO (tabertugliflozin/sitagliptin 5/100mg and 15/100mg tabs) IND: With metformin in pts w/ T2DM inadequately controlled w/ metformin and sitagliptin, or already controlled w/ metformin, sitagliptin and ertugliflozin, as individual drugs. AUX: Take in AM. DOS: Start=5/100mg once/d. Max=15/100mg once/d. OTH:
Xultophy=Insulin degludec+liraglutide: AVL: SubQ disposable pen3mLs/pen containing 100U/mL insulin degludec + 3.6mg/mL liraglutide. IND: T2DM. Not inidcated for T1DM or diabetic ketoacidosis. ADM: SubQ into thigh, upper arm or abdomen. Rotate site to avoid lipodystrophy. Any time of day w/ or without food, ideally same time of day. AE: Hypoglycemia, naus, diar, decreased appetitie, severe hypoglycemia<0.5%. CI: Not studied in combo w/ short acting insulins. DOS: Start=16U (16U degludec + 0.58mg liraglutide) once/d. Titrate up or down by 2U q 3-4d. Max=50U/d. Use alternate if pt insulin dose is <16U/d or >50U/d OTH: Essentially this is Tresiba+Victoza in one pen. Can be used w/ metformin and sulfonylureas.

 

Dipeptidyl Peptidase 4 Inhibitors (DPP-4I)

IND: T2DM (not as monotherapy). MOA: Inhibits DPP-4 which degrades GLP-1. EVD: A1C decreases 0.6-1%. ADM: T w/ or without food. COS: More expensive vs sulfonylureas and insulin. OTH: Typically prescribed w/ metformin. No weight gain or hypoglycemia.
alogliptin=Nesina: DI: Low potential for DIs. PK: Doesn’t inhibit CYPs. DOS: Adj for renal fxn. 25mg once/d. OTH: Kazano is a combination alogliptinmetformin.


linagliptin=Trajenta: PK: Met by 3A4. DOS: No adj for CrCl. 5mg once/d. OTH: Jentadueto is a combo=linagliptin+metformin.


saxagliptin=Onglyza: IND: Only DPP-4I not approved for monotherapy. DI: More 3A4 interactions vs sitagliptin PK: Met by 3A4/5 DOS: Adj for renal fxn. Std=2.5-5mg once/d.


sitagliptin=Januvia: DI: Low potential for 3A4 DIs vs saxagliptin. PK: Doesn’t inhibit CYPs. DOS: Adj for renal fxn. Std=100mg once/d (no titration). OTH: Janumet is a combo=sitagliptin+metformin (Avail as XR).


 

Glucagon-Like Peptide-1 (GLP-1) Agonists

AVL: SubQ. Often as add on to metformin, sulfonylurea, or LAIA. IND: T2DM. MOA: Binds to GLP-1 receptor which will increase glucose dependent insulin secretion and suppresses glucagon secretion during hyperglycemia. Increase GLP-1 activity 5-fold. EVD: Weight loss=1.5-2.8kg. Lowers A1C more than DPP4Is but more Naus at initiation. ADM: Inject 60min before breakfast or supper. AE: Hypoglycemia, Naus, Vom, Diar, increased HR, injection site rxn, acute pancreatitisrare. CI: CrCl<30. PRG: CI. DI: Causes delayed gastric emptying. DOS: Titrate dose q1-2w.
albiglutide=Eperzan: DOS: Once/w injections.


dulaglutide=Trulicity: DOS: No adj for CrCl. Start=0.75mg SubQ once/w. Maint=1.5mg SubQ once/w.


exenatide=Byetta=Bydureon: DOS: Adj for CrCl. Solution: Start=5μg SubQ BID Max=10μg BID SubQ. Suspension: 2mg/w.


liraglutide=Victoza: DOS: No adj for CrCl. Start=0.6mg SubQ once/d. Maint=1.2-1.8mg SubQ once/d without regard for meals.


 

Insulins

AVL: SubQ, IV. IND: T1DM and T2DM. EVD: Reduces A1C 1.5-2.5%. ADM: Inject in abdomen 5cm away from umbilicus, upper arm, anterior/lateral thigh, buttocks. Alcohol before not recommended (will sting). AE: Lipodystrophies, weight gain, hypoglycemia. DOS: T1DM: Typical=0.3-0.5 U/kg/d. “500 rule”: Take 500 and divide by units used/d. If 50 units used/d then 500/50=10. This means 1U of insulin covers 10g of carbs. Use “450 rule” if using R insulin instead of RAIA. T2DM: Insulin naïve=0.1-0.5 U/kg once daily. Maint~0.5-1.5 u/kg*d. Basal insulin should be ~50% of total insulin. Adjust 1 insulin at a time by 1-2U. OTH: Stability: 28d at room temp. Schedule II (available without Rx).
RAPID-ACTING INSULIN ANALOGUE (RAIA)
ADM: Inject <15min before meal. DOS: 1U~10-15g carbs. OTH: Clear liquid. Can mix w/ NPH if used immediately.


insulin aspart=NovoRapid: AVL: Avail vial, cartridge. PRG: Safe. LAC: Safe. PK: Onset=10-15min. Peak=1-1.5h. Duration=4-5h.


insulin glulisine=Apidra: AVL: Vial, cartridge, disposable. LAC: Safe. PK: Onset=10-15min. Peak=1-1.5h. Duration=4-5h.


insulin lispro=Humalog: AVL: Vial, cartridge, disposable. Avail as 200U/mL. PRG: Safe. LAC: Safe. PK: Onset=10-15min. Peak=1-1.5h. Duration=4-5h.


SHORT-ACTING/REGULAR (R)
ADM: Inject 30-45min before meal. OTH: Clear liquid. Can mix with all except long/extra acting


regular insulin=Humulin R=Novolin ge Toronto: AVL: Vial, cartridge. PRG: Safe. LAC: Safe. PK: Onset=0.5-1h. Peak=2-4h. Duration=5-7h. Abdomen site gives faster F.
INTERMEDIATE-ACTING/NHP (N)
ADM: If mixing draw up R first. Shake before giving. OTH: Cloudy liquid. Can mix with R and RAIA.


NPH insulin=Humulin N=Novolin-ge NPH: AVL: Vial, cartridge, Humulin Pen. PRG: Safe. LAC: Safe. PK: Onset=1-2h. Peak=4-10h. Duration=12-18h. DOS: Often given at HS +/- am dose.


LONG-ACTING INSULIN ANALOGUE (LAIA)
DOS: When switching from NPH decrease dose 20%. OTH: Clear liquid. Don’t mix.


insulin determir (D)=Levemir: AVL: Avail cartridge. LAC: Safe. PK: Onset=1-3.5h. Peak=none. Duration=16-24h. DOS: Once/d or BID. OTH: Neutral pH.


insulin glargine (G)=Lantus=Toujeo: AVL: Vial, cartridge, disposable. LAC: Safe. PK: Onset=1.5-4h. Peak=none. Duration=24h. DOS: Once/d or BID. OTH: Acidic pH (increased pain) to form microprecipitates which slows release.


ULTRA-LONG ACTING
insulin degludec=Tresiba: AVL: SubQ (3mL prefilled pens100 or 200U/mL). IND: T!DM (>2yo), Adults w/ T2DM. ADM: : Can inject in thigh, upper arm, or abdominal wall. Rotate sites. AE: Hypoglycemia, weight gain, lipodystrophy (rotate sites). DI: pioglitazone. PK: t1/2=25h. DOS: Once/d at any time of day (individualized dose). Start (insulin naïve)=10U once/d.
OTH: Can be used w/ PO antidiabetics and short or rapid insulin. 1U of degludec=1U of glargine. Refridgerate. Stable at room temp for 8w. Keep cap on to protect from light.


PREMIXED (R/N)
AVL: Humulin (30/70) Novolin GE (30/70), (40/60), (50/50). DOS: Inject once/d-TID but not HS. OTH: Can only mix in syringe (not pen).


 

Meglitinides

IND: T2DM as monotherapy if metformin and sulfonylurea not tolerated. Often used for people who skip/shift meals. MOA: Stimulates β cells to release insulin (shorter duration vs SUs). EVD: Possibly more effective for pc glucose levels vs SUs. ADM: Skip dose if skipping meal DI: gemfibrozil. 3A4. DOS: No dose adj for Cr Cl.
repaglinide=Gluconorm: ADM: T 0-30min before meals. DOS: 0.5mg BID-QID.


 

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors

AVL: PO. As monotherapy or w/ metformin. IND: T2DM. MOA: Blocks/reduces glucose reuptake in proximal tubule (part of the nephron in the kidneys). This is where 90% of reabsorption happens so glucose is urinated out. AE: UTI, candidiasis, increased urination, increased K, increased BUN/SCr, increased LDL, decreased BP, hypovolemia. Possible DKA, fracture risk. CI: CrCl<45. OTH: Some weight loss. No hypoglycemia.
canagliflozin=Invokana: AVL: PO. DI: UGT1A9/2B4. DOS: Adj for CrCl. 100 or 300mg once/d. OTH: Invonkamet=canagliflozin+metformin.


dapagliflozin=Forxiga: AVL: PO. CI: CrCl<60mL/min. DOS: Adj for CrCl. 5 or 10mg once/d. OTH: Xigduo=dapagliflozin+metformin.


empagliflozin=Jardiance: AVL: PO. EVD: Showed CV benefits in T2DM with CV disease. CI: CrCl<45mL/min. DOS: Adj for CrCl. 10-25mg once/d. OTH: Synjardy=empagliflozin+metformin.


ertugliflozin=Steglatro: AVL: PO (tab5, 15mg) IND: T2DM when metformin isn’t tolerated or with metformin +/- sitagliptin for better glycemic control. Shouldn’t be used for T1DM or w/ insulin. ADM: T in am w/ or without food. AE: Genital/urinary tract infections (especially females), increased urination, volume depletion leading to hypotension, diabetic ketoacidosis, lower limb amputation, kidney impairment/injury. CI: eGFR<45mL/min/1.73m2. Shouldn't start if eGFR=45-60mL/min/1.73m2.
DI: Can have additive volume depletion effect w/ diuretics (particularly w/ loops) . MON: Kidney function must be assessed before and periodically after. DOS: Start=5mg once/d. If necessary increase to Max=15mg once/d. No dose adj if eGFR >60mL/min/1.73m2. OTH: 4th SGLT2 to come out. Segluromet=Steglatro+metformin. Steglujan=Steglatro+sitagliptin.


 

Sulfonylureas (SUs)

IND: 2nd line for T2DM as monotherapy or combo. MOA: Stimulates β cells to secrete endogenous insulin (both basal and from meals). Also increases insulin sensitivity. EVD: Max effect at half of max dose. Lowers A1C by 1-1.5%. ADM: T w/ or before meal. Don’t take without. AE: Hypoglycemia2-30%, weight gain (1.6kg), alcohol induced flushing, low Na, rash. CI: T1DM, ketoacidosis. DI: Alcohol can cause flushing, changes in glucose, and tachycardia. DOS: Titrate dose q1-2w. OTH: Not CI if sulfa allergy but monitor (Theoretically not related). Body becomes less sensitive after long term use.
FIRST GENERATION
EVD:Typically not used due to PKs and DI.
chlorpropamide=Diabinese: AVL: PO. AE: Alcohol associated flushing, hyponatremia. PK: t1/2=36h. Duration=24-72h. DOS: Adj for CrCl. 100-500mg once/d.


tolbutamide=Orinase: AVL: PO. PK: t1/2=4.5-6.5h. Duration=6-12h. DOS: No adj for CrCl. 500-3000mg/d divided once-TID.


SECOND GENERATION
gliclazide=Diamicron: AVL: PO. Long-acting form=Diamicron MR. PK: t1/2=10h. Duration=12-24h. F=97%. One 80mg IR tab=30mg MR tab. DOS: Long-acting=30-120mg once/d. IR: 40-320mg divided Once-BID.


glimepiride=Amaryl: AVL: PO. PK: t1/2=5h. Duration=24h. DOS: Adj for CrCl. 1-4mg once daily.


glyburide=Diabeta=Euglucon: EVD: Only SU not CI in P + L but insulin preferred. ADM: AE: Higher risk of hypoglycemia vs other SUs (especially elderly/renal impairment). On BEERS list (avoid in elderly). PK: t1/2=10h. Duration=18-24h. COS: Cheap. DOS: Adj for CrCl. 2.5-20mg/d divided once/d or BID if >10mg. Max=10mg BID


 

Synthetic T4

levothyroxine=Synthroid=Eltroxin: AVL: PO (tab , IV, IM). IND: Replaces hormones produced by the thyroid. ADM: T in am 30-60min before food. Interacts with meds/ions so space 4hrs apart. AE: Increased HR, tremor, anxiety, D, exacerbation CVD. Hypothyroidism/low dose can cause hair loss. Warning: Prescribed in micrograms not miligrams. DI: Li decreases release of T3 and T4. PK: t1/2=6-7d. F=40-80% (can change w/ brand). PB=99%. Peak=2-4h. MON: (levels q4w when first starting). DOS: Start=25-50ug. Then adj accoding to bloodwork. Elderly typically require 20-30% lower dose.

 

Thiazolidinediones (TZDs)

IND: T2DM. MOA: Enhances insulin sensitivity by changing gene expression. EVD: Longer glycemic control vs metformin or glyburide. Lowers TGs, increases HDL. Mild BP lowering. Takes 6-12w for full glycemic effect. ADM: AE: Weight gain, edema, can increase LDL, HF, edema, fractures. Low risk of hypoglycemia as monotherapy. CI: HF, liver disease. MON: LFTs. OTH: Aka glitazones. Need written consent to prescribe. May cause ovulation in anovulatory women.
pioglitazone=Actos: AVL: PO. Warning: Possible risk of bladder cancer. DOS: 15-45mg once/d.


rosiglitazone=Avandia: AE: Possible increased MI risk. Possible 2-3X fracture risk increase. DOS: 4-8mg/d divided once-BID. OTH: Avandamet=rosiglitazone+metformin.


 

AVL: IND: MOA: EVD: ADM: AE: CI/Warning: PRG: LAC: DI: PK: COS: AUX: MON: DOS: OTH:
AVL: IND: MOA: EVD: ADM: AE: CI/Warning: PRG: LAC: DI: PK: COS: AUX: MON: DOS: OTH:


AVL: IND: MOA: EVD: ADM: AE: CI/Warning: PRG: LAC: DI: PK: COS: AUX: MON: DOS: OTH:


AVL: IND: MOA: EVD: ADM: AE: CI/Warning: PRG: LAC: DI: PK: COS: AUX: MON: DOS: OTH:


AVL: IND: MOA: EVD: ADM: AE: CI/Warning: PRG: LAC: DI: PK: COS: AUX: MON: DOS: OTH:


AVL: IND: MOA: EVD: ADM: AE: CI/Warning: PRG: LAC: DI: PK: COS: AUX: MON: DOS: OTH: