pc5 1.6 pharmacology of oral diabetes

biguanide, TZD

what meds reduce glucose uptake in the muscle

alpha glucosidase inhibitors

what meds work by absorbing glucose in the GI

SGLT2 inhibitors

what meds reabsorb glucose in the kidneys

DPP4 inhibitors, biguanide, TZD, GLP1 agonists

what meds increase hepatic glucose production

sulfonylureas, melitinides, DPP4 i , GLP 1 agonist

what meds target impaired insulin secretion

decrease hepatic gluconeogenesis, decrease glucose absorption, potential blunting of glucagon effects, increase insulin sensitivity

MOA of biguanides

metformin

what is a biguanide

no

does metformin stimulate insulin secretion

1-2%

how much does metformin lower A1c by

start low and go slow, take with food, XR reduces AE, take 1-2 months to titrate to top dose

dosing considerations with metformin

GI, vitamin B12 deficiency, neuropathy, hypogycemia(rare), lactic acidosis (rare)

AE of metformin

renal dysfunction, hepatic disease, dehydration, sepsis, hypoxemia, acute HF, MI

risk factors for lactic acidosis with metformin use

hold metformin before imaging and 2 days after

if a patient has renal dysfunction, is on metformin, and is having imaging done what should be done

malaise, myalgia, respiratory distress, abdominal discomfort

symptoms of lactic acidosis

over 45

at what eGFR can metformin be given at regular dose

under 30

at what eGFR should metformin be altogether avoided

initiation not recommended, assess risks/benefits, reduce dose by 50%

if a patient has eGFR 30-45 should they be given metformin

80 or over

at what age should metformin not be started, unless normal renal function

no

is metformin first line

neutral

metformin effect on weight

potential benefit

metformin effect on MACE

neutral

metformin effect on HF

neutral with dosing considerations

metformin effect on progression of CKD

fasting

does metformin effect fasting or postprandial blood glucose

yes

does metformin come in combinations with other agents

yes

can metformin be used for prevention of T2DM

inhibit SGLT2 in kidneys, block reabsorption of glucose

MOA of SGLT2i

Canagliflozin, dapagliflozin, empaliflozin, ertugliflozin

(ertu worst of these)

what SGLT2is have good data

0.5 to 1%, up to 1.5%

how much does SGLT2is lower A1c by

canagliflozin, dapagliflozin

what SGLT2is should not be started if eGFR is under 20

empagliflozin

what SGLT2is should not be started if eGFR is under 25

ertugliflozin

what SGLT2is should not be started if eGFR is under 45

20 to 59

at what eGFR should cangliflozin be dose adjusted

100mg daily

if a patient's eGFR is 20-59 what dose should they receive of canaglifozin

20-29

at what eGFR should empagliflozin be dose adjusted

10mg daily

if a patient's eGFR is 20-29 what dose should they receive of empagliflozin

genital mycotic infections, UTIs, hypotension, dizziness, increased LDL, DKA, fournier's gangrene, bone fractures(canaglifozin)

AE of SGLT2i

surgery

SGLT2i should be discontinued before __ to avoid DKA risk

CANVAS, CREDENCE

what trials show CV/CKD effects of canagliflozin

reduce risk of major CV in adults with type 2 DM and established CVD

the CANVAS trial led to what FDA indication of canagliflozin

reduce risk ESKD, double SCr, CV death, and hospitalization for HF for patients with T2DM and diabetic nephropathy

the CREDENCE trial led to what FDA indication of canagliflozin

EMPA-REG

what trials show CV/CKD effects of empagliflozin

reduce risk of CV death in adults with T2DM and established CVD

the EMPA-REG trial led to what FDA indication of empagliflozin

DECLARE-TIMI, DAPA-CKD

what trials show CV/CKD effects of dapagliflozin

to reduce risk of hospitalization for HF in patients with T2DM and CVD

the DECLARE-TIMI trial led to what FDA indication of dapagliflozin

reduce risk of eGFR decline, ESKD, CV death and hospitalization for HF in adults with CKD

the DAPA-CKD trial led to what FDA indication of dapagliflozin

VERTIS CV

what trials show CV/CKD effects of ertugliflozin

loss(intermediate)

what effect does SGLT2i have on weight

benefit for empagliflozin and canagliflozin

what effect does SGLT2i have on CV effect for MACE

benefit with cangliflozin, dapagliflozin, empagliflozin, ertufliglozin

what effect does SGLT2i have on CV on HF

benefit with canagliflozin, dapagliflozin, empagliflozin

what effect does SGLT2i have on progression of CKD

expensive, AE

cons of SGLT2i

once daily dosing, low risk of hypoglycemia, intermediate efficacy,weight loss, bp reduction

pros of SGLT2is

A1c or metformin

SGLT2i are recommended in pts with ASCVD or high ASCVD, HF, or CKD regardless of __ or __ use

increase insulin secretion, reduces postprandial glucagon, slows gastric emptying, enhances atiety

MOA of GLP-1 agonist

take 30 minutes before food/bev/other meds of the day, don't take with over 4 oz of water, slow and low dosing

Administration counseling for Rybelsus

DPP4 inhibitors

rybelsus shouldn't be combined with what

1%

how much does rybelsus reduce A1c

reduce MACE in T2DM, weight loss

what FDA indications does rybelsus have

SOUL

what trial showed reduction in MACE for rybelsus

loss

rybelsus effect on weight

benefits for non fatal MI

rybelsus effect on CV MACE

neutral

rybelsus effect on CV effect for HF

neutral

rybelsus effect on CKD progression

inhibit dipeptidyl peptidase 4 enzyme, slow inactivation of incretins, prolong GLP1/GIP

MOA of DPP4 inhibitors

alogliptin, linagliptin, saxagliptin, sitagliptin

DPP4is include what agents

0.5 to 1%

how much do DPP4is decrease A1c

once daily dosing, no dose titration, can be used in renal dysfunction, well tolerated

pros of DPP4is

linagliptin

what DPP4i doesn't need dose adjustment

alogliptin

what DPP4is need a renal dose adjustment for eGFR under 60

saxagliptin, sitagliptin

what DPP4is need a renal dose adjustment for eGFR under 45

low risk for hypoglycemia, joint pain, pancreatitis

AE of DPP4is

saxagliptin

what DPP4i has an increased risk of HF hospitalization

postprandial

do DPP4is affect fasting or postprandial glucose

cost, cyp3a4 interactions

cons of DPP4is

saxagliptin

what DPP4i is a CYP3A4 substrate

linagliptin

what DPP4i is a CYP3A4 weak to moderate inhibitors

neutral

what effect do DPP4is have on weight

neutral

what effect do DPP4is have on CV MACE

neutral or risk with saxagliptin

what effect do DPP4is have on CV HF

neutral

what effect do DPP4is have on CKD progression

stimulate PPARy, increase sensitivity to insulin, decrease hepatic glucose production

MOA OF TZDs

adipose, skeletal, smooth muscle, liver

where is PAAR present

pioglitazone

what agents are TZDs

1-2%

how much do TZDs reduce A1c

fluid retention, edema, weight gain, bone fractures, bladder cancer

AE for TZDs

NYHA class III or IV HF

(boxed warning)

contraindications to TZD

liver disease

(check LFTS before)

TZDS should be used in caution in people with what

delayed

do TZDs work immediately or is there delayed onset

cheap, good durability, may improve lipids, may reduce all cause mortality/nonfatal MI/stroke, decrease risk of recurrent stroke

positives of TZD

delayed onset, caution in liver disease, ineffective in insulin deficiency, increased risk of HF

negatives of TZD

gain

effect of TZD on weight

potential benefit

effect of TZD on CV MACE

increase risk

effect of TZD on CV HF

neutral

effect of TZD on CKD progression

stimulate insulin release from B cells, inhibit K channels on B cell, depolarize B cells and secrete insulin

MOA of sulfonyl urea

glimepiride, glipizide, glyburide

sulfonylureas include what agents

1-2

(higher when first diagnosed)

how much do sulfonylureas reduce A1c

geriatric, starting new regimen, renal insufficiency

who needs a lower dose of sulfonylurea

hypoglycemia

why should sulfonylureas be started at a lower dose