Diabetes Drugs

Front 1

biguanides (metformin) moa

Back 1

"** Decreases hepatic glucose output (primary)
** Decreases insulin resistance in periphery (secondary
** Decreased or delayed absorption of carbohydrates "

Front 2

biguanides (metformin) efficacy

Back 2

"** DEC FPG by 50-70 mg/dl
** DEC A1C 1.5-1.7%
** DEC PPG 83 mg/dl
** DEC TG 10-20% , DEC TC 5-10% , ** DEC LDL and INC HDL (slight) "

Front 3

biguanides (metformin) ADR

Back 3

** GI effects (D/N/V, Abdominal bloating, flatulence, and metallic taste). ** Minimal ADR @ low dose ** Lactic Acidosis rare (wkness,fatig,malaise,exhaution, rapid breathing). ** Megaloblastic anemia ** No weight gain / Induce weight loss

Front 4

biguanides (metformin) drugs

Back 4

** Metformin (Glucophage 500, 800, 1000) ** Meformin (Glucophage XR) 500, 750 mg (see table for notes for more info.

Front 5

biguanides (metformin) metabolism/excretion

Back 5

** BioAvail @ 60% ** Excreted unchaged in urin ** T1/2 about 6 hours (dose 2-3 x daily, XR dosed QD wc)

Front 6

biguanides (metformin) - clinical use

Back 6

** First line treatment in T2DM + Medical nutrition therapy + exercise ** Keep dosing at 2000 mg/d ** Has favorable lipid profile (EXPT when given with insulin **Primarly lower FBG **Be ware of CIs

Front 7

biguanides (metformin) - monitoring

Back 7

** FPG ** A1C Q 3 months if > 7% ** SrCr at baseline then Q12Months or more frq if > 65 YO ** HgB, HcT, RBC @ baseline then every 12 months ** LFTs at baseline ** Check B12 and folate anemia if present

Front 8

biguanides (metformin) - ci

Back 8

"** All contraindications due to risk of lactic acidosis Major contraindication is renal
o Scr ≥1.4 Females
o Scr ≥ 1.5 Males
o Age > 80 w/ normal renal function OK ** NO in chronic hepatic dysfunction ** NO in hypoxic disease state (CHF, CHD, COPD, sev infection, Chronic R-OH) ** A/Chr Metabolic Acidosis ** Iodinated IV Radiocontrast Dye (stop metformin 48 hr after) "

Front 9

biguanides (metformin) - pt education

Back 9

"** D/C if weak, tired or dizzy and have
trouble breathing ** Can make you sick if two to four alcoholic
drinks a week **Kid problems - metformin may build up in body ** Notice a metalic taste **N/V/D ** Tell Surgeon if on Met ** If using Radiodye tell MD and hold 48 hr after test"

Front 10

THIAZOLIDINEDIONES (Glitazones, or TZDs) - moa

Back 10

"** Inc insulin sens at the muscle by ag on the peroxisome
PPARγ which results in increased glucose
uptake (primary)
** Decrease hepatic glucose output (secondary) "

Front 11

THIAZOLIDINEDIONES (Glitazones, or TZDs) - efficacy

Back 11

"** DEC FPG by 30-65 mg/dl
** DEC A1C 0.6-1.9%
** DEC PPG 40-65 mg/dl
** Pioglitazone: DEC TG 26% and INC HDL 8-14%
** Rosiglitazone: INC HDL, INC LDL 5-19% "

Front 12

THIAZOLIDINEDIONES (Glitazones, or TZDs) - adr

Back 12

**Mild to moderate edma **DO NOT USE IN CLASS 3 / 4 HF ** Weight gain (Rosi +1.2 - 3.5, Piog +2-8 kg) **Mild Anemia

Front 13

THIAZOLIDINEDIONES (Glitazones, or TZDs) - drugs

Back 13

"Pioglitazone
(Actos)
15, 30, 45 mg Rosiglitazone
(Avandia)
2, 4, 8 mg
"

Front 14

THIAZOLIDINEDIONES (Glitazones, or TZDs) - metabolism/excretion

Back 14

** Onset and duration poorly correlated w/ half-life b/c of MOA. Onset 3 weeks, Max at 4-8 weeks. **Piog Metab in liv to actv metabolites by CYP2C8, 3A4 and 15 to 30 % excreted in urin, rest in feces **Rosi Metab in liv to inact metab 2C8, 2C9, and 2/3 in urin and 1/3 in feces

Front 15

THIAZOLIDINEDIONES (Glitazones, or TZDs) - clinical use

Back 15

** 2nd / 3rd line after met - no hypogly ** Monotherapy / combo w/ met / SFU / INS. ** Decr insulin Req and improv cont ** Usually in combo w/ MET or SFU monotherapy **Can be used in decreased renal funct ** PIOG is preferred

Front 16

THIAZOLIDINEDIONES (Glitazones, or TZDs) - monitoring

Back 16

FPG, A1C Q3Months if > 7%, Weight, Edema, S/sx of HF (peri edema, SOB, fatigue), S/sx of hepatotoxity (unexp nausea, vomiting, ab pain) LFTs at baseline then measure periodically. **Do not start if LFTs > 2.5 x ULN ** F/U if ALT > 1 -2.5 x ULN ** DC if ALT > 3x ULN

Front 17

THIAZOLIDINEDIONES (Glitazones, or TZDs) - ci

Back 17

"**Active liver disease or serum ALT levels > 2.5 x upper limit of normal
** Patients with New York Heart Association Class 3 or 4 heart failure due to fluid
retention and edema.
** Use cautiously in patients with edema or heart failure. "

Front 18

THIAZOLIDINEDIONES (Glitazones, or TZDs) - pt education

Back 18

"** Medications in this group don't cause blood sugar to drop too low. But if you take
other diabetes medications along with pioglitazone or rosiglitazone, your blood
sugar might drop too low.
** This drug may cause weight gain.
** This drug may cause swelling in the legs or ankles. Tell your doctor if this occurs.
** Report any signs of heart failure (shortness of breath, edema, fatigue). "

Front 19

Sulfonylureas (SFU) - moa

Back 19

"** Stimulate insulin secretion from the beta-cells of pancreas
** Decrease insulin resistance
** Decrease hepatic glucose output (HGO) "

Front 20

Sulfonylureas (SFU) - efficacy

Back 20

"** DEC FPG by 50-70 mg/dL
** DEC A1C 1.5-1.7%
** DEC PPG 92 mg/dL "

Front 21

Sulfonylureas (SFU) - adr

Back 21

"** Hypoglycemia
** Weight gain (5-10 lbs) "

Front 22

Sulfonylureas (SFU) - drugs

Back 22

"Glyburide
(Diabeta, Micronase
1.25, 2.5, 5 mg)
(Glynase Pres Tab
1.5, 3, 6 mg)
Glipizide
(Glucotrol 5, 10 mg)
(Glucotrol XL
2.5, 5, 10 mg)
Glimepiride
(Amaryl 1, 2, 4 mg) "

Front 23

Sulfonylureas (SFU) - metabolism / excretion

Back 23

"** Some accumulate as unchanged drug or active metabolites in renal failure.
o Glyburide metabolites are active
** Some are metabolized to inactive or mildly active compounds: glipizide, glimepiride "

Front 24

Sulfonylureas (SFU) - clinical use

Back 24

** 2nd line after MET - LEAST expensive. ** Avoid glburide in frail elderly ** Glip / Glim preferred agents **Dosing - start low, go slow for 1 to 2 weeks until max dose is achieved. Exceeding max dose will increase ADRs but will not decrease blood [ ] further. **Predisposed to Hypogly: The elderly, and R-OH-ics.

Front 25

Sulfonylureas (SFU) - monitoring

Back 25

"** S/Sx of hypoglycemia ** Fasting serum glucose levels ** A1C Q3Months if > 7%. **Hypogly - shaking, palpitations, sweating, dizziness, anxiousness,
hunger, impaired vision, weakness, fatigue, headache, irritability"

Front 26

Sulfonylureas (SFU) - ci

Back 26

"** Use drugs cautiously in elderly and those with decreased renal function for those
agents with active metabolites **DRUG INTERACTIONS: ** Beta-blockers: Beta-blockers may enhance the hypoglycemic effect of glyburide and
mask tachycardia as an initial symptom of hypoglycemia. "

Front 27

Sulfonylureas (SFU) - pt education

Back 27

"** This drug may cause your blood sugar to go too low.
** Eat regularly scheduled meals.
** Emphasize importance of following prescribed diet, exercise, and medical regimen.
** Suggest drug be taken with food if GI upset occurs.
** Provide pt w/ instruction on how to monitor blood glucose, urine glucose, and ketone
levels
** S/sx hypo and hyperglycemia and what to do if these occur. S/Sx of hyperglycemia "

Front 28

Meglitinides (Glinides) - moa

Back 28

** Stimulates insulin secretion from β-cells of pancreas

Front 29

Meglitinides (Glinides) - efficacy

Back 29

"** DEC FPG by 61 mg/dl
** DEC A1C 1.7%
** DEC PPG 48 mg/dl (mainly used for this) "

Front 30

Meglitinides (Glinides) - adr

Back 30

"** Hypoglycemia (take only with meals)
** Weight gain "

Front 31

Meglitinides (Glinides) - drugs

Back 31

"Repaglinide
(Prandin)
0.5, 1, 2 mg
Nateglinide
(Starlix)
60, 120 mg "

Front 32

Meglitinides (Glinides) - metabolism/excretion

Back 32

"** Very short-acting compared to the sulfonylureas (onset 1 hour; duration 4 hours)
** Predominantly metabolized by the liver to inactive products (92%); 8% excreted
unchanged by the kidneys
** Metabolism inhibited by CYP3A4 drugs "

Front 33

Meglitinides (Glinides) - clinical use

Back 33

"** 3rd
or 4th
line agent. May be used in combination with metformin or thiazolidinediones. **Short acting and targets PPG levels **use in pts who have high PPG and close to normal FPG **given w/c good for pts with irregular eating habits ** If not response by SFU move to Meglit"

Front 34

Meglitinides (Glinides) - monitoring

Back 34

"** Post-prandial glucose levels
** S/Sx of hypoglycemia
** Fasting serum glucose levels
** A1C q 3 months "

Front 35

Meglitinides (Glinides) - ci

Back 35

none

Front 36

Meglitinides (Glinides) - pt education

Back 36

"** Emphasize importance of following prescribed diet, exercise, and medical regimen.
** S/sx hypo and hyperglycemia and what to do if these occur.
** Tell patient to take drug before meals, usually 15 minutes before start of meal;
however, time can vary from immediately preceding meal to up to 30 minutes before
meal.
** Tell patient that if a meal is skipped or an extra meal added, he should skip the dose
or add an extra dose of drug for that meal. "

Front 37

Alpha-GLUCOSIDASE INHIBITORS - moa

Back 37

"** Delays absorption of complex carbohydrates (CHO) and slows glucose absorption from
the gut into the blood "

Front 38

Alpha-GLUCOSIDASE INHIBITORS - efficacy

Back 38

"** DEC FPG 20-30 mg/dl
** DEC A1C by 0.5-1%
** DEC PPG by 25-50 mg/dl "

Front 39

Alpha-GLUCOSIDASE INHIBITORS - adr

Back 39

"Dose-dependent flatulence, cramps, abdominal distention, and diarrhea due to
fermentation of CHOs in the colon. "

Front 40

Alpha-GLUCOSIDASE INHIBITORS - drugs

Back 40

Acarbose / Miglitol (Don't worry too much about them, RARELY USED!!!!!)

Front 41

Alpha-GLUCOSIDASE INHIBITORS - clinical use

Back 41

"**TARGETS PPG 4th
or 5th
line agent. Targets PPG. Least effective in lowering A1C (0.5-1%).
Take doses with first bite of each meal.
Monotherapy not associated with hypoglycemia
Combination with SFU, may have hypoglycemia
DO NOT MANAGE HYPOGLYCEMIA WITH COMPLEX CARBOHYDRATES!
Use oral glucose tabs or glucose gel "

Front 42

Alpha-GLUCOSIDASE INHIBITORS - monitoring

Back 42

"** Post-prandial glucose levels
** S/Sx of hypoglycemia (if used in combination with hypoglycemic agents)
** Fasting serum glucose levels
** A1C q 3 months, if >7%
** LFTs q 3 months with acarbose for 1st
year "

Front 43

Alpha-GLUCOSIDASE INHIBITORS - ci

Back 43

"** Contraindicated in cirrhosis, inflammatory bowel dz, chronic intestinal dz,
hepatic/renal dz "

Front 44

Alpha-GLUCOSIDASE INHIBITORS - pt education

Back 44

"** Taking this medication may cause stomach problems such as gas, bloating and
diarrhea that most often go away after you take the medication for awhile.
** If you take this medication with a sulfonylurea (glyburide, glipizide), then you should
use glucose tabs or gel to treat low blood sugars. "

Front 45

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS - moa

Back 45

"Slows the inactivation of incretin hormones. Concentrations of the active intact hormones are increased
by DPP-4 inhibitors, thereby increasing and prolonging the action of these hormones (GLP-1, GIP) to increase insulin
secretion and decrease hepatic glucose output. "

Front 46

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS - efficacy

Back 46

"**DEC FPG by 13-25 mg/dl
**DEC A1C 0.5-0.7%
**DEC PPG 49-62 mg/dl "

Front 47

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS - adr

Back 47

"**Diarrhea, abdominal pain, nausea; URI symptoms
**Post-marketing data reported 88 cases of acute pancreatitis for sitagliptin "

Front 48

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS - drugs

Back 48

"Sitagliptin (Januvia®)
25, 50, 100 mg
*Merck;
FDA Approved 10/17/06
Saxagliptin (Onglyza®)
2.5, 5 mg
* Bristol-Myers Squibb;
FDA Approved 7/31/09 "

Front 49

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS - metabolism/excretion

Back 49

** 79% excreted unchanged in urine; metabolism minor pathway

Front 50

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS - clinical use

Back 50

"** Monotherapy or in combination with other antidiabetic agents
** A1C lowering is only about 0.5-0.8%
** Long-term safety has not been established
** Expensive!
"

Front 51

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS - monitoring

Back 51

"** Fasting serum glucose levels
** A1C q 3 months, if > 7%
** Scr at baseline and periodically thereafter
"

Front 52

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS - ci

Back 52

NO CI's except for pts with hypersensitivity for something

Front 53

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS - pt education

Back 53

** Educate on monitoring parameters.

Front 54

BILE ACID SEQUESTRANTS -moa

Back 54

"** Increased prevalence of hypertriglyceridemia and gallbladder disease in DM or
insulin resistance
** Bile acid synthesis is increased, the bile acid pool is expanded, and bile acid
excretion is increased in DM "

Front 55

BILE ACID SEQUESTRANTS -
efficacy

Back 55

"**DEC FPG 14 mg/dl
**DEC A1C by 0.5% "

Front 56

BILE ACID SEQUESTRANTS- adr

Back 56

"Constipation, Nausea, Dyspepsia, Abdominal pain
Increases triglycerides (TG) ~5% "

Front 57

BILE ACID SEQUESTRANTS- drugs

Back 57

"Colesevelam
(WelChol
®)
625 mg "

Front 58

BILE ACID SEQUESTRANTS- metabolism /excretion

Back 58

** Not absorbed therefore not metabolized systemically

Front 59

BILE ACID SEQUESTRANTS- ci

Back 59

"**May cause increases in triglyceride levels ~ 5% **Higher TG when using combination of SFU and insulin. **Smaller increase in TG are seen when in comb w/ metformin **Decrease absorption of fat soluble vitamines. **Contraindicated in patients with triglyceride levels > 500 mg/dL
**History of bowel obstruction due to constipation DRUG INTERACTIONS: Phenytoin
** Increased seizure activity
** Decreased phenytoin levels
Warfarin
** Decrease in INR
Thyroid Hormone Replacement Therapy
** Increased TSH
"

Front 60

BILE ACID SEQUESTRANTS- pt education

Back 60

"** Colesevelam is the first and only medication approved to reduce both glucose levels
and low density lipoprotein cholesterol levels (LDL-C).
** Forty percent of patients with type 2 diabetes also have high LDL-cholesterol.
** Use only if patient requires both LDL lowering on top of their control of diabetes.
Remember that it can increase TG, so do not use in patients with elevated TG. "

Front 61

INJECTION: INCRETIN-MIMETIC: BYETTA® (EXENATIDE) - moa

Back 61

"** Exenatide is a synth. hormone that mimics the effects of endogenous ** Like insulin and amylin, GLP-1 is secreted in response to food, however it is secreted
by the L-cells mostly in the ileum and colon, and not by the pancreas.
** Beta-cells: increases insulin secretion and increases β-cell growth/replication
(differentiation /proliferation)
** Alpha-cells: inhibits glucacon secretion
** Liver: reduces hepatic glucose output by inhibiting glucagon release
** CNS: promotes satiety
** Stomach: slows gastric emptying incretins such
as human glucagon-like-peptide 1 (GLP-1) "

Front 62

INJECTION: INCRETIN-MIMETIC: BYETTA® (EXENATIDE) - efficacy

Back 62

"** DEC A1C 0.4% – 0.86%
** DEC weight 0.9 – 2.8 kg Indications
** Type 2 diabetes as adjunct to SFU, metformin or TZD
** NOT approved for use with insulin "

Front 63

INJECTION: INCRETIN-MIMETIC: BYETTA® (EXENATIDE) - adr

Back 63

"** Doesn’t cause hypoglycemia alone, but can cause hypoglycemia when used in
combination with SFU
** Nausea 44%
** Weight loss "

Front 64

INJECTION: INCRETIN-MIMETIC: BYETTA® (EXENATIDE) - drugs

Back 64

" Dosage form and Storage
** Pre-filled pens
** 5 mcg/dose,
** 10 mcg/dose Dosage and Admin Type 2 DM
** Initial dose
** 5 mcg SQ BID within 60 minutes before morning and evening meal.
** If after 1 month, adequate glycemic control is not achieved, can
increase to 10 mcg BID
** Administered subcutaneously in thigh, abdomen or upper arm.
** If given in conjunction with metformin, dose reduction not required, but dose
of sulfonylurea should be decreased empirically "

Front 65

INJECTION: INCRETIN-MIMETIC: BYETTA® (EXENATIDE) - metabolism/excretion

Back 65

"** Peak: 2.1 hours after SQ injection
** Half-life: 2.4 hours
** Elimination by glomerular filtration
** No dosage adjustment required in mild-moderate renal impairment; clearance
reduced in renal dialysis patients
** No data in pts with acute or chronic hepatic insufficiency "

Front 66

INJECTION: INCRETIN-MIMETIC: BYETTA® (EXENATIDE) - clinical use

Back 66

"** 2nd or 3rd line treatment in type 2 patients according to updated algorithm in 2009
** Byetta would require 2 SC injections daily using a pre-filled pen
** If patients are willing to give themselves injections, consider insulin before initiating
Byetta
** Induces weight loss "

Front 67

INJECTION: INCRETIN-MIMETIC: BYETTA® (EXENATIDE) - monitoring

Back 67

"Monitoring ** A1C
** FPG
** Renal function DRUG INTERACTIONS ** Due to itseffects on gastric emptying, exenatide may reduce the rate and extent of
absorption of PO drugs.
** Caution in patients receiving medications which require rapid
absorption from the GI ** Admin of medications 1 hour prior to the use of exenatide has been
recomm by the manuf when optimal drug absorp and peak levels
are impt to therapeutic effect (such as with abx and/or PO contraceptives). "

Front 68

INJECTION: INCRETIN-MIMETIC: BYETTA® (EXENATIDE) - ci

Back 68

"** Gastrointestinal disease: Not recommended to be used in patients with
gastroparesis or severe gastrointestinal disease
** Renal impairment: Use not recommended in severe renal impairment (CrCl < 30
mL/minute).
** Pancreatitis:
** Cases of acute pancreatitis (including hemorrhagic and necrotizing with
some fatalities) have been reported; monitor for unexplained severe
abdominal pain, and if pancreatitis is suspected, discontinue use.
** Do not resume unless an alternative etiology of pancreatitis is confirmed.
** Consider alternative antidiabetic therapy in patients with a history of
pancreatitis.
"

Front 69

INJECTION: INCRETIN-MIMETIC: BYETTA® (EXENATIDE) - pt education

Back 69

"** Administer Byetta injection within a 60 minute period before morning and evening
meals. Do not administer after meal.
** Consume alcohol with caution; may cause hypoglycemia.
** You may experience nausea (small, frequent meals, frequent oral care, sucking
lozenges, or chewing gum may help),
** Report persistent nausea, diarrhea, or dizziness.
** Proper use and storage of injection pen. "

Front 70

AMYLIN-MIMETIC: SYMLIN® (PRAMLINTIDE) - moa

Back 70

"** Synthetic analog of human amylin cosecreted with insulin by pancreatic beta cells
** Modulates gastric emptying, slowing the rate at which food is absorbed from the
intestine
** Prevents an increase in serum glucagon, therefore inhibiting hepatic glucose output
** Increases the feeling of satiety, suppressing one’s appetite, leading to weight loss "

Front 71

AMYLIN-MIMETIC: SYMLIN® (PRAMLINTIDE) - efficacy

Back 71

"Indications
** Type 1 diabetes as an adjunct to mealtime insulin
** Type 2 diabetes as an adjunct to mealtime insulin with or without SFU or Metformin

Efficacy
** DEC A1C 0.49 – 0.57%
** DEC weight 1.1 kg – 1.5 kg "

Front 72

AMYLIN-MIMETIC: SYMLIN® (PRAMLINTIDE) - adr

Back 72

"**Hypogly when in combo with insulin **Nausea in 1/3 to 1/2 pts. Tolerance to nausea therapy continues: lower indicence if pramlintide is graduatly tirated to recommended dosage ** Weight loss
** Abdominal pain
** Fatigue
** Headache "

Front 73

AMYLIN-MIMETIC: SYMLIN® (PRAMLINTIDE) - metabolism/excretion

Back 73

"** Half-life: 48 minutes
** 50% bound to serum albumin or blood cells
** Metabolism: has one active metabolite
** Excretion: renal "

Front 74

AMYLIN-MIMETIC: SYMLIN® (PRAMLINTIDE) - clinical use

Back 74

"** 4th
or 5th
-line treatment in type 2 patients in combination with insulin.
** 2nd
-line agent in type 1 patients
** Patient should already be receiving SC injections for insulin
** Symlin would require at least 2 more injections
** Induces weight loss "

Front 75

AMYLIN-MIMETIC: SYMLIN® (PRAMLINTIDE) - monitoring

Back 75

"** A1C
** Hypoglycemic history
** Body weight "

Front 76

AMYLIN-MIMETIC: SYMLIN® (PRAMLINTIDE) - ci

Back 76

"
Warnings and Contraindications
** Poor compliance with current insulin regimen
** Poor compliance with SMBG
** A1C > 9%
** Recurrent hypoglycemia requiring assistance in last 6 months
** Patients with hypoglycemia unawareness
** Confirmed diagnoses of gastroparesis
** Pediatric patients "

Front 77

AMYLIN-MIMETIC: SYMLIN® (PRAMLINTIDE) - pt education

Back 77

"** Administer injection immediately before meals containing >250 Kcal or >30 gm of
carbohydrate.
** This medication cannot be mixed with insulin. Use a different syringe for each
medication.
** If you experience hypoglycemic reaction, contact prescriber immediately. Always
carry quick source of sugar with you.
** Monitor glucose levels as directed by prescriber. ** Pts may xperi Nausea (small fq meals, oral care, lozenges, and chewing gum may help) ** Pts may xperi HA, fatigue, or dizziness ** Report N/V and hypogly reactions"