Tx of T2DM - Oral Agents Flashcards
What are the outcomes of large diabetes prevention studies based on lifestyle changes and meds?
- studies have shown that the biggest impact on preventing DM is lifestyle changes: increase exercise, decrease calories and fat, and losing weight
- Da Qing Study
- Finnish DM Prevention Study: 58% RRR incidence of DM
- DM Prevention Program: 58% RRR
- Toranomon Study
- Indian DPP
- studies show that meds can also prevent DM but not as effectively as lifestyle changes: TRIPOD, STOP-NIDDM, DPP, DREAM
given a pt at risk for DM, apply the lifestyle change outcomes to reduce or prevent profession to DM
- counsel of weight loss (5-10%)
- increase physical activity (at least 150 min/week)
Given a pt at risk for DM, select the medication to reduce or prevent progression to DM based on the outcomes of the prevention studies
metformin
ADA criteria for the use of metformin for prevention of DM in a pt at high risk for DM/preDM
- ADA recommends considering metformin for those at the highest risk:
- IFG + IGT plus other risk factors:
- A1c > 6%
- HTN
- positive family hx
- obese
- <60
- low HDL
- high TG
State the outcomes of the DCCT on the development or progression of microvascular diabetes complications
this study proved normalizing blood glucose could prevent or delay progression of diabetic complications
- in the primary prevention group:
- 76% RRR in the development of retinopathy
- 34% reduction in nephropathy
- 60% reduction in neuropathy
- secondary prevention group:
- 54% RRR in retinopathy
- 43% reduction in nephropathy
state the outcome of the UKPDS concerning the reduction of microvascular complications
- drug therapy group vs. diet group to control blood glucose
- outcome: 25% reduction in microvascular complications
glycemic goals of therapy for a nonpregnant adult with T2DM
- a1c
- preprandial blood glucose
- A1c: <7%
- BG: 80-130
identify pts who may safely achieve an A1c of < or equal to 6.5%
- those with a short duration of DM
- long life expectancy
- no significant cardiovascular dz
identify the pts who need less stringent A1c goals
- people who are at risk for severe hypoglycemia
- have a limited life expectancy
- have advanced complications and/or severe co-morbid diseases
- have had DM for many years and have trouble achieving <7% despite use of multiple glucose lowering meds
What are patient risk factors for the development of prediabetes/diabetes
- impaired fasting glucose
- impaired glucose tolerance test
- A1c > 5.7-6.4%
- BMI > 30
- < 60 yo
- women w/ hx of gestational DM
given a pt w/ prediabetes, choose a tx plan to reduce their risk for developing DM
- lifestyle changes are tx of choice
- if meds needed: metformin
- tx other cardiovascular risk factors: BP, lipids, smoking
- monitor for development of DM annually
Place in therapy for metformin in the tx of T2D
if lifestyle changes fail to achieve glycemic goals and have not achieved an A1c <7.5% then metformin is the drug of choice
expected clinical effect of metformin on the patient’s blood glucose control
- lowers fasting plasma glucose concentrations by about 55 mg/dl
- reduces A1c by 1-2%
- no hypoglycemia
- no weight gain
contraindications to metformin
- renal function
- unstable CHF
- liver dz
- alcohol abuse
- pregnancy/lactation
renal function guidelines for metformin use
- DO NOT use in CKD stages 4 and 5
- do not initiate therapy at stage 3B but may continue use at 1000mg max dose
- avoid initiating therapy at stage 3A if expected to become unstable but may continue use at 2000mg max
- CKD stages 1 and 2: max dose 2550 mg
initial dose of metformin
500 mg once or twice daily (Letassy said she starts w/ once daily)
titration dose of metformin
- start at 500 mg daily
- dose should be increased at the rate of 1 tab weekly
- up to a max dose of 2500 mg per day
*her example:
500mg daily x 1 week; increase to 500 mg BID x 1 month; then add 500 mg where needed
MoA of metformin
- decreases hepatic glucose production from gluconeogenesis and glycogenolysis
- increases glucose uptake in the muscle by increasing movement of glucose transporters to the cell membrane and by increasing their sensitivity to insulin and glucose
ADRs of metformin
GI are MC
- early satiety and anorexia
- nausea w/ or w/o vomiting, anorexia, diarrhea, bloating, and abdominal discomfort
what needs to be monitored when taking metformin?
- B12 concentrations
- some pts may need replacement
what is the expected clinical effect of the sulfonylureas (SU) and meglitinides on the pts BG control?
- fasting BG to drop 60-70 mg/dl
- A1c reduction of 1-2%
contraindications to SUs and meglitinides
- T1D
- DM d/t pancreatic resection
- hx of adverse rxns to SUs or sulfa drugs
- stress: emotional, severe infection, trauma, major surgery
- significant renal or hepatic dz
- those predisposed to significant hypoglycemia
MoA of SUs and meglitinides
-stimulate beta cells to release more insulin
ADRs associated w/ SUs and meglitinides
- GI: nausea, heartburn
- Derm: rash and puritis; sulfa structure and hypersensitivity
- hypoglycemia
what is the expected clinical effect of pioglitozone on the pts BG control?
- average decrease in A1c is 1.5% (in pts w/ a baseline of 9%) and is seen after 12-14 weeks
- average decrease in A1c when added to another agent: 0.8-1.3%
(the numbers don’t agree with this but the packet says it’s more effected when used in combo)
contraindications to the use of pioglitazone
- Class III and IV CHF (it precipitates heart failure)
- anemia
- impaired liver function
- T1D
- pregnancy
MoA of pioglitazone
- interact w/ a nuclear receptor (peroxisome proliferator activated receptor gamma)
- when activated, it binds w/ response elements on DNA, altering transcription of many genes that regulate carb and lipid metabolism
- results: increase in gene expression of glucose transporters
- decreases insulin resistance in peripheral tissue
- decreases hepatic glucose production
ADRs associated w/ pioglitazone
- weight gain**
- edema
- anemia (dilutional effect)
- heart failure and exacerbation of CHF
- skeletal effects: decrease in bone density and increased risk of fx
- increased risk of heart dz
- macular edema (rare)
- increase in serum transaminases
what is the expected clinical effect of the DPP-4 inhibitors (januvia) on the pts BG control?
0.6-0.8% drop in A1c
contraindications to the use of DPP-4 inhibitors
- T1D
- DKA
- caution in: risk of heart failure, hx of pancreatitis, and CrCl < 45
given a pts renal function and Januvia use, select the max daily dose
- max daily dose: 100 mg daily
- moderate renal insufficiency (CrCl 30-<50): 50mg daily
- severe renal insufficiency (CrCl < 30) or w/ ESRD requiring dialysis: 25mg daily
MoA of DPP-4 inhibitors
- they inactivate DPP-4
- DPP-4 is an enzyme that deactivates GLP-1
- GLP-1 functions to slow gastric emptying and stimulates the pancreas to produce insulin in response to a meal
ADRs of DPP-4 inhibitors
- stuffy/runny nose
- sore throat
- URI
- HA
- serious hypersensitivity rxns
what is the expected clinical effect of the SGLT2 inhibitors (invokana, farxiga, jardiance) on the pts BG control?
- A1c decrease of about 1%
- some weight loss d/t increased excretion of glucose
contraindications of SGLT2 inhibitors
- do not use in pts w/ severe renal imapirment (eGFR < 45) ESRD, or on dialysis
- T1D
MoA of SGLT2 inhibitors
- inhibit sodium glucose transporters in the proximal tubules of the nephron
- this inhibition prevents the reabsorption of flitered glucose in the kidney
- glucose passes through the nephron and out into the urine
ADRs associated w/ SGLT2 inhibitors
- increased risk of yeast infections and UTIs
- risk of hyperkalemia
- increase in LDL
- hypotension
- increased risk of acute renal failure
- decline in hgb and hct
- euglycemic DKA ***
risk factors for euglycemia DKA d/t SGLT2 inhibitors
- major illness
- reduced fluid and food intake
- reduced insulin dose
- type 2 DM
**the packet doesn’t specifically state the risk factors, this is just what I interpreted them as
symptoms of euglycemia DKA d/t SGLT2 inhibitors
- mild elevation of glucose (<200)
- high anion gap metabolic acidosis
- elevated blood or urine ketones
- most pts have T2D
given a child w/ T2D, select the most appropriate therapy
- Insulin therapy indications:
- ketosis or DKA
- unclear if T1 or T2
- unusual cases like a random BG >250 or A1c >9%
- all other cases:
1. lifestyle changes: nutrition interventions and physical activity
2. metformin - confirm T2
- start low (500mg) d/t GI side effects
- monitor for glycemic deterioration
- add insulin if needed
3. test A1c every 3 months - target = <7%
- intensify tx if needed
