Lecture 4 (T2DM Management) Flashcards
(131 cards)
1
Q
MOA of Metformin
A
lowers hepatic glucose production
can also enhance sensitivity
increase glucose utilization via action in the gut
2
Q
What dosing levels from metformin?
A
start slow - initiate 250-500 mg
desired 850-1000 mg BID
max dose 850 mg TID
3
Q
What is the efficacy of metformin?
A
reduce A1C to 1.5%
decrease TG and LDL
4
Q
List DI with metformin
A
Cimetidine
Dolutegravir
alcohol
contrast media
5
Q
Common AE metformin
A
GI (Diarrhea, N, general abdominal discomfort)
6
Q
Less Common AE metformin
A
metallic taste
vitamine B12 deficiency with long term use
hypoglycemia
7
Q
Precautions for Metformin
A
lactic acidosis –> caused by decrease in arterial pH
Sx weakness, malaise, myalgias, heavy labored breathing
this can be a rare SE of metformin
8
Q
Major CI of metformin R
A
renal impairment with ClCr < 60 ml/min
if 45-59 1500mg/d
if 30-44 1000mg/d
CI when <30
9
Q
Other CI of metformin
A
History of lactic acidosis
Severe liver disease
Alcohol abuse
Radiologic procedures (iodinated contrast)
Acute illness (severe infection, trauma)
Severe dehydration
10
Q
When combining with metformin if the pt has
degree of hyperglycemia, addition will have
A
BG lowering efficacy & durability
11
Q
When combining with metformin if the pt has
risk of hypoglycemia, add will have
A
risk of inducing hypoglycemia
12
Q
When combining with metformin if the pt has
weight, the add will have
A
effect of weight
13
Q
When combining with metformin if the pt has
clinical CVD, addition will have
A
effect on CV outcomes
14
Q
When combining with metformin if the pt has
comorbidities (renal,CHF,hepatic) addition will have
A
CI and S/E
15
Q
When combining with metformin if the pt has
access to treatment, agent needs to have
A
cost and coverage
16
Q
MOA of Sulfonylureas
A
they enhance the secretion of insulin by binding to SU receptors on the beta cells of the pancreas
This leads to closing of K+ channels and opening of calcium channels which stimulates insulin secretion
they stimulate both basal and meal-stimulated insulin release
17
Q
List some of the 2 gen of SUs
A
glyburide
gliclazide
glimepiride
18
Q
When is glyburide CI? R
A
<60 ml/min
19
Q
What is the CI for gliclazide? R
A
> 30 ml
Caution with 30-60
20
Q
Efficacy of SUs
A
reduce A1C –> 1 to 1.5%
works quickly
21
Q
Common AE of SU
A
hypoglycemia
weight gain
22
Q
Uncommon AE of SUs
A
nausea, rash, photosensitivity
23
Q
CI of SUs
A
pregnancy and breastfeeding
CI for both hepatic and renal impairment
24
Q
DI of SUs
A
Sulfonamides, salicylates, warfarin
alcohol
cimetidine
clarithromycin
fluconazole
NSAIDs
beta-blockers
MAOIs
25
Drugs in Meglitinides
repaglinide
26
MOA of meglitinides
binds to a site adjacent to the SU receptor, resulting in stimulation of the secretion of insulin from the pancreas
27
Efficacy of meglitinides
lowers A1C 1-1.5%
works primarily to decrease PPG
28
AE of repaglinide
hypoglycemia
weight gain
similar to SU but less SE
29
DI of repaglinide
increase 3A4 inhibitors (cyclosporine, grapefruit)
increase 2C8 (gemfibrozil, clopidogrel)
decrease 3A4 inducers (carbamazepine)
30
What drugs are alpha-glucosidase inhibitors?
acarbose
31
MOA of acarbose
α-Glucosidase enzymes in the small intestine are responsible for the breakdown of polysaccharides into absorbable glucose
Acarbose inhibits these enzymes, hence there is a delay in the rate of digestion of CHO’s and glucose absorption
32
Efficacy of acarbose
reduce AC1 0.5-0.8%
reduce PPG levels
33
Main AE of acarbose
flatulence and diarrhea
34
Other AE of acarbose
bloating, abdominal pain
hypoglycemia
35
DI of Acarbose
digestive enzyme preparations
may decrease digoxin effect
36
What pts to be cautious with acarbose?
IBD or GI conditions
37
CI with acarbose R
<25 ml/min or severe liver disease
38
What drugs are in thiazolidinediones?
rosiglitazone
pioglitazone
39
MOA of thiazolidinediones
bind to PPAR-y receptors which are primarily found in adipose tissue
enhance insulin sensitivity at muscle, liver, and fat tissues
40
Efficacy of thiazolidinediones
lower A1C 1-1.5%
TG - P decrease, ros is neutral
LDL - P neutral, ros is increase
HDL - both increase
41
DI of thiazolidinediones
anything metabolized by CYP 2C8
increase with inhibitors (TMP)
decrease with inducers (rifampicin)
42
What is the caution with thiazolidinediones? R
<60m/min
mainly metabolized by liver (liver disease)
43
AE of thiazolidinediones
peripheral edema
new-onset/worsening of HF
weight gain
increase distal fractures in postmenopausal women
44
Rare AE of thiazolidinediones
Macular edema: report any blurred vision, loss of sight
Anemia: not very common; long-term side effect
Pio: possible ↑ bladder cancer risk?...dont use if history of
Rosi: possible ↑ MI
45
Cardiovascular safety of TZDs
there was a study that showed that there is an increase risk of MI
but there was another study that disproved it
because of this all new diabetes meds require a CV outcome trial to show that these meds are not bad for the heart
46
List the examples of GLP-1 receptor agonists
semaglutide
exenatide (daily and weekly)
liraglutide
dulaglutide
lixisenatide
47
List the examples of DPP-4 inhibitors
linagliptin
sitagliptin
saxagliptin
48
MOA of DPP4 inhibitors
block the enzyme DPP4 which rapidly hydrolyzes incretins, thus enhancing the action of endogenous incretins
49
Efficacy of DPP4 inhibitors
decrease A1C 0.7
50
Dosing for Sitagliptin (normal and renal adjustment)
100 mg Once daily
30-44 --> 50 mg Once daily
<30 --> 25 mg Once daily
51
Dosing for saxagliptin (normal and renal adj.)
5 mg Once daily
30-44 --> 2.5 mg Once daily
<30 --> use with caution
52
CI for saxagliptin
avoid in ESRD, dialysis
53
Dosing for linagliptin (normal and renal adj.)
5 mg Once daily
no dose adjustment needed
54
Dosing for alogliptin (normal and renal adj.)
25 mg Once daily
30-44 --> 12.5 mg Once daily
<30 --> 6.25 mg Once daily
55
Most common AE of DPP4i
overall, well tolerated meds
no hypo on their own
weight neutral
headache
nasopharyngitis
URTI
56
Rare AE of DPP4i
hypersensitivity rxn
bullous pemphigoid
joint pain
pancreatitis
57
Cautions with DPP4i
history of pancreatitis
58
DI for DPP4i
combined SU or insulin --> increase hypoglycemia
avoid GLP1RA (similar MOA)
59
DI for saxagliptin
clearance is reduced / enhanced with strong CYP 3A4 inhibitors and inducers
60
DI for linagliptin
clearance is enhanced with strong 3A4 inducers
61
MOA of GLP1RA
stimulate insulin secretion in a glucose-dependent manner
lowers glucagon, slow gastric emptying
increase satiety
62
Storage requirements for GLP1RAs
in the fridge for most of the time
at home most can be out of the fridge for 2-4 wks
semaglutide --> always room temp
63
Which GLP1RAs are short acting?
exenatide
lixisenatide
64
Which GLP1RAs are long acting?
liraglutide
exenatide
liraglutide
semaglutide
65
What is the formulation of oral semaglutide?
po bioavailable, when co formulated with SNAC
but only 1% makes the journey
66
Renal dosing considerations for dulaglutide
<15
67
Renal dosing considerations for liraglutide
<15
68
Renal dosing considerations for semaglutide SC
<15
69
Renal dosing considerations for semaglutide PO
<30
70
Renal dosing considerations for exenatide QW
CI <30
caution in 30-50
71
Renal dosing considerations for exenatide
CI <30
caution in 30-50
72
Renal dosing considerations for lixisenatide
CI < 30
limited data
73
Efficacy of GLP1RAs
decreases A1C about 1-1.5%
longer are more potent than short acting
works on both FPG and PPG
74
Common AE for GLP1RAs
N/V/D (nausea)
75
Some tips to minimize nausea for GLP1RAs
tell pt what to expect
stop eating when full
eat smaller portions and eat slowly
consider end of day dosing
stay hydrated and drink cold water when nauseous
76
Rare AE of GLP1RAs
acute gallstone disease
acute pancreatitis
increase cancer risk
retinopathy
77
GLP1RAs affect on weight
weight loss
amount various
was not due N/V/D
78
DI with GLP1RAs
since these drugs decrease gastric emptying
oral contraceptives
antibiotics
narrow TI drugs
79
T/F
GLP1RAs help with glucose but not CV or renal
False it has been shown to help all of those and HF
80
MOA SGLT2 Inhibitors
tends to be overexpressed in those with T2DM
responsible for glucose reabsorption from the kidneys
81
Effects on BG for SGLT2i
decrease A1C by 0.5-0.8% as an add on agents
works on both FPG and PPG
82
What is the limiting factor for SGLT2i?
they work in the kidneys so the pt. will have to have functioning nephrons to work
83
What are the effects on weight for SGLT2i?
~2-3kg weight loss
84
Dosing for SGLT2i
the lower dose works also just as well as the higher (very little benefit for more)
85
What is the renal dosing for SGLT2i?
if renal is <45, it will not be very beneficial
but some will stay on because they have a renal protection
86
What is a caution with SGLT2i and renal?
there will be a lower of eGFR of about 5 after the start of this medication
87
Most common AE for SGLT2i?
increase urination
increase thirst
can cause mycotic genital infections (will have once)
88
What is the management and prevention of genital mycotic infections?
recommended to pee, rinse and then wipe
89
What are some rare AE for SGLT2i?
DKA (caused by dehydration)
can happen without low blood sugar
90
Other effects on levels with SGLT2i?
mild increase in LDL and HDL
decrease in TGs
mild decrease in BP (SBP/DBP)
91
DI with SGLT2i
watch for diuretics
92
What are some rare AE for canagliflozin?
Might be amputation (with other risk)
might be increase risk of bone fracture (also other risks)
fournier's gangrene
93
What is fournier's gangrene?
very rare condition that involves pain, swelling, tenderness in genital region
94
What is the link between Empagliflozin?
decrease CVD
has CV protection
superior for MACE
95
List the SGLT2i
dapagliflozin
canagliflozin
empagliflozin
96
What is the link between SLGT2i with renal disease?
helps with decrease ERSD
decrease in renal or CV death
renal protective (not just for DM can work for normal pt too)
97
What is the link between SLGT2i with heart failure?
decrease in hospitalization (both DM or not)
Cardiac protection
decrease hHF or CV death
98
What is the link between SLGT2i with secondary prevention?
Empa and Cana decrease MACE
99
What is the link between SLGT2i with primary prevention?
Dapa did not decrease MACE but others did make a difference
100
Does T1DM or T2DM use mixed insulin more often?
T2DM tends to use mixed more often
101
What are some barriers to insulin for the pt?
More complexity
Sense of failure
Fear of hypo
Needle phobia
Fear/denial of disease progression
“my aunt went on insulin and lost her foot”
102
What are some barriers to insulin for the HCPs?
More complexity
Fear of hypo
Patient’s cognitive ability to handle it
103
What are the benefits to premixed insulins?
less injections
easier to understand
104
What are the three major options for T2DM starting insulin?
Basal insulin + antihyperglycemic
Basal and bolus
biphasic (premixed) insulin
105
What is the benefit to only initiated with basal?
simplicity
minimization of weight gain and hypoglycemia
keeping oral meds on board helps with insulin sensitization
106
Define overbasilization
basal insulin has a ceiling effect
they over take insulin and it stops helping as much
need to switch to have both basal and bolus
107
What happens if basal insulin / oral/SC pharmacotherapy is not doing the trick?
evaluate/add another antihyperglycemics
basal insulin/GLP1RAs combo products
go to basal and bolus
108
If patients are willing to do MDI, start by introducing 1 prandial insulin at a time, explain the process
Start with largest meal; 2-4U
Titrate by 1-2U/week until FPG and PPG at target
As insulin gets added, consider removing secretagogues
Monitor for effectiveness (BG targets) as well as hypoglycemia
109
List some factors that are used to choose a second line drug after metformin
Clinical CV disease?
Hypoglycemia
Affect on weight
Renal function
Degree of hyperglycemia
Other comorbidities (i.e. heart failure)
Cost
Patient preference
110
MOA of Tirzepatide
a GIP and GLP1 dual agonist
It enhances the secretion of insulin in response to food (increase in BG) and reduces glucagon (in a glucose dependent manner)
111
Common AE for Tirzepatide
GI (N/D/V)
dyspepsia, constipation and abdominal pain
hypo
112
Efficacy of Tirzepatide
Decrease A1C between 1.8-2.5%
113
Affect on Weight with Tirzepatide
average was losing around 25.8 lb
114
DI of Tirzepatide
gastric emptying --> BC or similar medication
115
CI for Tirzepatide
GLP1RAs
116
What is the new thinking of treatment strategy?
instead of treating to fail
try to be preemptive and help with things early before it gets really bad
117
Should we use antiglycemic agents in T1DM?
no as they might be beneficial but it does not outway the risks (mainly hypo)
118
When is preconception care essential?
for women with pre-existing DB to optimize pregnancy outcomes
119
What are the A1C goals for the different stages of pregnancy?
pre <7
during <6.5
120
What are some increase risks with poorly controlled DB and pregnancy?
risk of miscarriage, stillborn and malformations
121
What is the disease monitored for during pregnancy for a DB?
retinopathy
HTN
CKD
122
What meds can you still take for T2DM and pregnancy?
metformin, glyburide or insulin
123
What meds should you stop take for T2DM and pregnancy?
ACEi /ARB
Statins
124
What drugs are used for gestational DB?
insulin is the drug of choice
but can use metformin and glyburide
125
What is the first line tx for GDM?
diet and exercise (for about 2 wks)
if it is not working after 2 wks then they go on meds
126
What makes DB in children more complicated?
Psychological risks
Eating disorders
Insulin omission
Need access to a dietician
Smoking cessation
Contraception
127
What is the targets for T1DM?
A1C targets of <7 or 7.5% for all children <18 yo
FPG - 4-8 mmol/L
2hr PPG - 5-10 mmol/L
more relaxed as worried about hypo is higher
128
When a child/adolescent is diagnosised with T2DM, what is the plan?
the whole family is talked to, as it is more a situation more than just the child
129
What is first line for T2DM in adolescents?
metformin
or metformin + basal insulin
or metformin + liraglutide
130
What is needed to be considered for T2DM in elderly?
higher risk of hypo
limited use of SUs, TZDs
DPP4i over SU
when using insulin, use basal analogues
more relaxed targets
131
What is the A1C targets based on for the elderly?
mainly the level of independent
