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PHAR152 > Diabetes 5 > Flashcards

Diabetes 5 Flashcards

1
Q

What are examples of SGLT2 inhibitors?

A

dapagliflozin (Forxiga)
canagliflozin (Invokana)
empagliflozin (Jardiance)

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2
Q

What is the role of SGLT2?

A

transporter that is responsible for glucose reabsorption (90%) from the glomerular filtrate
overexpressed in those with T2DM

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3
Q

What is the MOA of SGLT2 inhibitors?

A

inhibit SGLT2, thereby decreasing the reabsorption of glucose, and increasing urinary glucose excretion
insulin-independent action

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4
Q

True or false: hypoglycemia occurs with SGLT2 inhibitors

A

false
they have no insulin stimulation

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5
Q

What are the effects of SGLT2 inhibitors on blood glucose?

A

decreases A1C 0.5-0.8% as add-on agent
-meta analysis show it has similar BG lowering ability to other
agents when added to metformin
works on both FPG and PPG
begin working quickly (FPG decreases within 2 weeks)

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6
Q

What is required for SGLT2 inhibitors to work?

A

functioning nephrons
hence BG lowering ability declines with decreased renal function

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7
Q

What is the effects of SGLT2 inhibitors on weight?

A

~2-3kg average weight loss
occurs through a loss of 60-80g/d glucose in urine
plateaus at 26 weeks; is sustained

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8
Q

What is the dosing of SGLT2 inhibitors?

A

are oral, OD medications
start at low dose; effects on A1C, cardio/renal outcomes are not dose-dependent
renal: eGFR <45, no longer effective for BG (but beneficial for cardio renal protection)
-can continue empa 10mg, dapa 10mg, and cana 100mg

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9
Q

What occurs to kidney function upon initiating an SGLT2 inhibitor?

A

very early decrease in kidney function, about 5ml/min in eGFR
-this is not kidney damage, it is a hemodynamic effect that is
reversed upon dc
measure at baseline and then 2-3 weeks later
-if decrease is 20-25%: recheck at 3 months
-if the decrease is 25-30%: recheck within 7 days
-if decrease is >30%: lower dose or stop and investigate

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10
Q

What are the adverse effects of SGLT2 inhibitors?

A

most common:
-increased urination
-increased thirst
-mycotic genital infections (females>males, usually once)
less common/rare:
-UTIs (recently found no increased risk)
-DKA

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11
Q

What are the effects of SGLT2 inhibitors on lipids and blood pressure?

A

lipids (~5%):
-mild increase in LDL and HDL
-decrease in TGs
blood pressure:
-mild decrease in SBP and DBP (3-5mmHg and 2mmHg)

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12
Q

What is the management and prevention of genital mycotic infections for a patient on an SGLT2 inhibitor?

A

pee, rinse, wipe

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13
Q

What are some contraindications and precautions with SGLT2 inhibitors?

A

dehydration potential: use cautiously in patients at risk for volume depletion effects
-elderly, loop diuretics, low SBP, CKD, ACEI/ARBs
DKA risk: rare, but severe if it occurs
-increased risk in illness, long-standing T2, T1DM, major
surgery, alcohol, low carb diets, insulin omission, extreme
exercise

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14
Q

What are drug interactions with SGLT2 inhibitors?

A

concomitant use with diuretics may increase risk of hypovolemia and hypotension

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15
Q

Does canagliflozin increase risk of amputations?

A

probably not
caution in history of amputation, diabetic neuropathy, PAD, diabetic foot ulcers

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16
Q

Does canagliflozin increase risk of bone fracture?

A

no increased risk in those not at risk to begin with
caution in older adults with high fracture risk, fall risk, and hydration status

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17
Q

What is Fourniers gangrene?

A

pain, swelling, tenderness in genital region
cases reported with canagliflozin but not in mass

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18
Q

Which SGLT2 inhibitor is currently covered under the SK formulary for treatment of Class II and III heart failure?

A

dapagliflozin

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19
Q

Summarize the cardio renal benefits of SGLT2 inhibitors.

A

dose doesnt seem to matter
secondary CV prevention in those with ASCVD: empa and cana decreased MACE
primary CV prevention: dapa did not decrease MACE
in patients with HF: they decrease hHF or CV death
in patients with CKD: they decrease cardio renal outcomes

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20
Q

What are the premixed insulins available for T2DM?

A

premixed regular insulin-NPH (cloudy)
-30% regular/70% NPH (Humulin 30/70)
-30% regular/70% NPH (Novolin 30/70)
-40% regular/60% NPH (Novolin 40/60)
-50% regular/50% NPH (Novolin 50/50)
premixed insulin analogues (cloudy)
-30% aspart/70% aspart protamine crystals (NovoMix 30)
-25% lispro/75% lispro protamine (Humalog Mix25)
-50% lispro/50% lispro protamine (Humalog Mix50)

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21
Q

When should premix regular be injected? When should premix analogues be injected?

A

premix regular: 30-45 minutes before starting a meal
premix analogues: 15 minutes before or after a meal

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22
Q

What are the barriers to insulin?

A

from patient perspective:
-more complexity
-sense of failure
-fear of hypo
-needle phobia
-fear/denial of disease progression
from HCP perspective:
-more complexity
-fear of hypo
-patients cognitive ability to handle it

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23
Q

What are the options when initiating insulin with a T2DM patient?

A
  1. basal insulin + antihyperglycemic medications
    -usually initiated as 10U at bedtime
    -can start at 5U if lean/frail/concerns about hypo
    -if long-acting can start in AM if prefer
  2. basal and bolus insulin
  3. biphasic (premixed) insulin
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24
Q

How is basal insulin titrated in T2DM?

A

1U hs or 1-2U q2-3d days (slower titration for Toujeo and Tresiba) until FBG 4-7mmol/L
do not increase if >2 hypo episodes in 1 week, or nocturnal hypo

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25
Q

Why is it preferred to initiate with basal insulin in T2DM?

A

simplicity
minimization of weight gain and hypoglycemia
keeping oral meds on board helps with insulin sensitization

26
Q

What is the ceiling effect of basal insulin?

A

0.5U/kg/d

27
Q

What should we start to consider thinking that basal insulin has hit its ceiling effect?

A

T2 patient requires > 0.5U/kg/d
A1C high despite FBG being at target
2hr PPG > 3mmol/L higher than pre-meal reading
bedtime BG >3mmol/L higher than AM FBG

28
Q

How is iGlarLixi dosed?

A

uncontrolled A1C on:
-<30U/d basal insulin or GLP1RA treatment–>15U starting
->30 to <60U/d basal insulin–>30U starting
titration: 15U–>30U–>60U (maximum doses)
-weekly based on FPG

29
Q

How is IDegLira dosed?

A

uncontrolled A1C on:
->16U to <50U/d basal insulin or <1.8mg/d liraglutide–>16U
titration: 16U–>50U (maximum dose)
-every 3-4 days based on FPG

30
Q

How do we dose bolus insulin in T2DM?

A

if patient willing to do 2 injections/d, BID split-mixed insulin is an option
if patient willing to do MDI, start by introducing 1 prandial insulin at a time:
1. start with largest meal; 2-4U
2. titrate by 1-2U/week until FPG and PPG at target
3. as insulin gets added, consider removing secretagogues
4. monitor for effectiveness (BG targets) and hypo

31
Q

Describe how to choose therapy for T2DM.

A

see slide 31 slide deck 5

32
Q

Describe how to adjust or advance therapy in T2DM when A1C is not at target and/or change in clinical status.

A

see slide 32 slide deck 5

33
Q

What should be taken into consideration when choosing a second line drug for T2DM?

A

clinical CV disease?
hypoglycemia
affect on weight
renal function
degree of hyperglycemia
other comorbidities (i.e. heart failure)
cost
patient preference

34
Q

What is a new anti-hyperglycemic that has been approved by Health Canada in November 2022?

A

tirzepatide

35
Q

What is the MOA of tirzepatide?

A

GIP and GLP1 dual agonist
-enhances secretion of insulin in response to food and reduces
glucagon (in a glucose dependent manner)

36
Q

What is the indication of tirzepatide?

A

adults with T2DM

37
Q

What are the adverse effects of tirzepatide?

A

nausea
diarrhea
vomiting
also dyspepsia, constipation, abdominal pain
hypo: increased risk when added to basal insulin/SU

38
Q

What are the effects of tirzepatide on heart rate, blood pressure, and weight?

A

increase in HR of 2-4 BPM
decrease in SBP (6-9mmHG) and DBP (3-4mmHg)
decrease in 25.8 lbs shown in SURPASS-4

39
Q

What are some storage and injection tips for terzepatide?

A

inject to abdomen, thigh, upper arm (rotate sites)
store in fridge: can store unrefrigerated for up to 21d

40
Q

Can dapagliflozin, liraglutide, or empagliflozin be used in T1DM?

A

longer-term results on safety and efficacy are needed before approval beyond T2DM

41
Q

What is the traditional treatment strategy in T2DM?

A

diagnosis–>lifestyle–>metformin–>other oral agents–>insulin
typically treat to fail

42
Q

What is an alternative treatment strategy in T2DM?

A

induce glycemic remission:
-thought there is reversible dysfunction early on in T2DM
-short term insulin therapy (2-5wks) to modify disease and
preserve beta-cell function
-remission does not last forever, maintenance therapy unclear

43
Q

What is the A1C target pre-pregnancy? What about during pregnancy?

A

pre-pregnancy: <7% (ideally <6.5% if safe)
pregnancy: <6.5% (6.1% if possible)

44
Q

What are the FBG and 2hr PPG goals in pregnancy?

A

FBG <5.3mmol/L
2hr PPG <6.7mmol/L

45
Q

What does poor controlled diabetes increase the risk of during pregnancy?

A

miscarriage
stillborn
malformations

46
Q

When should diabetic women see an ophthalmologist during pregnancy?

A

before conception, 1st trimester, prn during pregnancy and within 1st year post-partum

47
Q

What are some potential embryopathic meds?

A

ACEI/ARB
statins

48
Q

What can be used for therapy of T1DM during pregnancy? What about T2DM?

A

T1DM: insulin
T2DM: can continue metformin, glyburide, or insulin

49
Q

What is the DOC for diabetes (T1 and T2) once pregnancy occurs?

A

insulin
-metformin and then glyburide may be considered as
alternatives for those women unwilling to use insulin

50
Q

What is first line therapy for gestational diabetes?

A

diet and exercise
-if dont achieve glycemic targets within 2wks–>pharmacotherapy
nutrition counseling is important

51
Q

What is second line therapy for gestational diabetes?

A

insulin
alternatives: metformin and glyburide

52
Q

When should women who experienced gestational diabetes be re-screened postpartum?

A

6wks to 6 months postpartum to see if glycemia is resolved

53
Q

How long is breastfeeding encouraged to be done to reduce the risk of developing diabetes for both mother and child?

A

4 months

54
Q

Does the excretion of insulin through breast milk pose a risk to the infant?

A

no because its degraded in the GIT before reaching systemic circulation

55
Q

Why is diabetes more complicated with children?

A

psychological risks
eating disorders
insulin omission
need access to a dietician
smoking cessation
contraception

56
Q

What is the treatment of T1DM in children?

A

whenever possible; intensive insulin (MDI or CSII)

57
Q

What are the targets for A1C, FPG, 2hr PPG in T1 children?

A

A1C: <7 or 7.5% for all children <18yo
FPG: 4-8mmol/L
2hr PPG: 5-10mmol/L

58
Q

What are the pharmacologic options for TD2M in children and adolescents?

A

metformin: 1st line
metformin and basal insulin if more marked hyperglycemia
metformin + liraglutide: FDA approved >10yrs

59
Q

Which anti-hyperglycemic drugs should we limit the use of in elderly?

A

SU
TZD
choose DPP4i over SU

60
Q

Which type of insulin is preferred for an elderly T2 diabetic?

A

basal

PHAR152 (21 decks)

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