Diabetes Lecture 3 Flashcards
Oral Agents
Biguanides Sulfonylureas Meglitinides TZD’s Alpha glucosidase inhibitors Incretin Mimetics DPP-IV inhibitors GLP-1 agonists Amylin mimetics Sodium glucose co-transporters
Biguanides MOA
Inhibits hepatic glucose production and increases insulin sensitivity to peripheral tissues
Biguanides Drugs
Glucophage, Riomet, Glucophage XL, Glumetza (Metformin)
Biguanides Place in Therapy and Dose
1st line (monotherapy or with other agents or insulin) especially for type 2 1000mg BID (titrate the dose)
Biguanides A1C
1.5-2%
Biguanides Side Effects
GI (diarrhea)…take with meals
Lactic acidosis (rare)
Vitamin B12 deficiency (very frequent)
Weight loss
Biguanides Absolute CI
Cr ≥ 1.4 (women) or Cr ≥ 1.5 (men)
Biguanides Precaution
> 80 years old
Liver disease and excessive alcohol intake (more than 2 drinks per day)
Acute CHF, infection, surgery
Sulfonylureas Drugs
1st Generation: Rarely used due to increased side effects, NOT USED ANYMORE
2nd Generation
Amaryl (glimepiride)
Glucotrol, Glucotrol XL (glipizide)
Micronase (glyburide)
Sulfonylureas MOA
Increases insulin production from the beta cells in the pancreas
Sulfonylureas Places in Therapy
Monotherapy or conjunction with basal insulin or other oral agents
Sulfonylureas A1C and Dose
A1C= 1-2%
Typically dosed once or twice daily
Skip dose is patient is not going to be eating a meal
If renal insufficiency is noted use Glipizide
Sulfonylureas Side Effects and Precautions
Hypoglycemia
Weight gain- using more insulin
Precautions= Sulfa Allergy
Meglitinides Drugs
Starlix (nateglinide)
Prandin (repaglinide)
Meglitinides MOA
Increases insulin production from the beta cells in the pancreas (binds to a different receptor than the sulfonylureas)
Meglitinides Place in Therapy
Monotherapy or conjunction with other oral agents
Note: After 3-5 years there is a reduction in the benefit seen due to loss of beta cell function
Meglitinides A1C and dose
A1C Reduction: 0.5-2%
Dose:
Shorter half lives than sulfonylureas
Take right before a meal (3 times a day)
Meglitinides Side Effects
Less hypoglycemia than sulfonylureas
Less weight gain than sulfonylureas
TZD’s Drugs
Avandia (rosiglitizone)
Actos (pioglitizone)
TZD’s MOA
Increases insulin-dependent glucose disposal and decreases hepatic glucose output by decreasing insulin resistance in the periphery and in the liver
TZD’s Place in Therapy
Monotherapy or conjunction with other oral agents or insulin
TZD’s Side Effects
Weight gain
Edema
Increase ovulation in women(metformin can do this too)
Hepatic dysfunction
Avandia: Increases likelihood of an MI and has negative lipid effects NO LONGER IN US
Actos: Positive effects on lipids but increased risk of bladder cancer
TZD’s A1C and Dose
A1C Reduction: 0.5-1 %
Dose:
Takes several weeks to see an effect (up to 8 weeks)
TZD’s CI
Stage 3 or 4 heart failure
TZD’s Precaution
Do not initiate in patients with active liver disease or ALT > 2.5x normal
Monitor LFTs in all patients at baseline, every 2 months for 12 months, and then periodically; d/c drug if ALT > 3x ULN
Alpha Glucosidase Inhibitors Drugs
Glyset (miglitol)
Precose (acarbose)
Alpha Glucosidase Inhibitors MOA
inhibits enzyme that hydrolyzes complex starches and sugars into readily absorbable molecules, delaying absorption of glucose
Alpha Glucosidase Inhibitors Place in Therapy
Monotherapy or conjunction with other oral agents…especially high post-prandial glucose values
Alpha Glucosidase Inhibitors A1C and Dose
A1C- 0.5- 1%
Typically dosed with food (3 times a day)
Titrate the dose to allow for adjustment to GI effects
Alpha Glucosidase Inhibitors Side Effects
GI!!! Flatulence, diarrhea
If hypoglycemia occurs…must take simple sugars (glucose)
Alpha Glucosidase Inhibitors CI
GI disorders
Conditions that would risk bowel perforation
DPP-IV Inhibitors Drugs
Januvia (sitagliptin)
Onglyza (saxagliptin)
Tradjenta (linagliptin)
Nesina (alogliptin)
DPP-IV Inhibitors Place in Therapy
Type 2 DM and used in addition with other oral agents
DPP-IV Inhibitors A1C and Dose
A1C- 0.4-0.85% Dose: All gliptin’s are dosed once daily orally Sitagliptin, saxagliptin and alogliptin Require renal dose adjustments
DPP-IV Inhibitors Side Effects and Precautions
Side Effects:
Headache
URI
Weight loss/weight neutral
Precautions:
Pancreatitis has been reported
GLP-1 Analogs Drugs
Byetta (exenatide)
Bydureon (XR exenatide)
Victoza (liraglutide)
GLP-1 Analogs Place in Therapy
Adjunctive therapy in patients with type 2 diabetes who are taking metformin, a sulfonylurea, TZD or a combination of the above but have not achieved adequate glycemic control
GLP-1 Analogs A1C and Dose
A1C= 1-1.5%
Dose:
Inject in abdomen, thigh, or upper arm
Exenatide
Twice daily injection (1 hour before meals and no closer than 6 hours from next dose)
Need to dose adjust for renal impairment.
XR Exenatide
Once weekly injection.
Liraglutide
Once daily injection. Do not need to time with meals
GLP-1 Analogs Side Effects and Precautions
Side Effects:
GI upset
Some hypoglycemia (if combined with sulfonylurea)
Some weight reduction
Precaution:
Take antibiotics and birth control pills at least 1 hour prior to injecting
GLP-1 Analogs Storage and Black Box Warning
Storage:
Keep refrigerated, keep away from light, discard after 30 days
Black Box Warning:
Liraglutide: Thyroid carcinoma (found in rats)
Amylin Analog Drug
Symlin (pramlintide)
Amylin Analog Place in Therapy
Adjunct therapy in type 1 or type 2
Amylin Analog Dose
Dose: Inject in abdomen, thigh, or upper arm Immediately prior to major meals (3 times a day) Type 1: Initial, 15 mcg SQ Maintenance, titrate at 15 mcg increments to 30 and then to 60 mcg SQ as tolerated…if 30mcg is not tolerated D/C Type 2: Initial, 60 mcg SQ Maintenance, 120 mcg SQ as tolerated
Amylin Analog A1C
0.3-0.6%
Amylin Analog Side Effects
GI (nausea, vomiting, anorexia)
Headache
Some weight loss (at least weight neutral)
Risk of hypoglycemia when administered with insulin
Slows gastric emptying thus avoid other agents that do the same
Take other medications either 1 hour before or 2 hours after injection
Patients that should be excluded from Amylin Analog
Poor compliance with current insulin regimen
Poor compliance with monitoring blood glucose
A1C > 9%
Recurrent severe hypoglycemia in the past 6 months
Hypoglycemia unawareness
Confirmed gastroparesis diagnosis
Use of drugs that stimulate gastric motility
Pediatric patients
Sodium Glucose Co-Transporters Inhibitors (SGLT-2)
SGLT-1 and SGLT-2 receptors in kidneys
SGLT-2: Responsible for glucose reabsorption
DM pts have more SGLT-2 receptors
Leads to 200-300 k/cal per day lost by inhibiting SGLT-2
Random Facts about SGLT-2
Mainly dosed once daily and does require renal dose adjustment.
Reduction in A1C (~1% reduction compared to placebo)
Reduction in FPG
Reduction in weight by about 4-7 pounds
Slightly increase LDL
Modestly lower BP
ADE: Polyuria, thirst, nasopharengitis, UTI’s, genital infections
What medicines work on the brain
dopamine agonists
pramlintide
What medicines work on the liver
Metformin
TZD’s
What medicines work on the GI
GLP-1 agonists
alpha glucosidase inhibitors
pramlintide
What medicines work on the muscle/fat
Metformin
TZD’s
What medicines work on the kidney
SGLT2 inhibitors
What medicines work on the pancreas
insulin, GLP-1 agonists, DPP-4 inhibitors, sulfonylureas, pramlintide (alpha cells only) meglitinides
