Diabetes 5 Flashcards
What are examples of SGLT2 inhibitors?
dapagliflozin (Forxiga)
canagliflozin (Invokana)
empagliflozin (Jardiance)
What is the role of SGLT2?
transporter that is responsible for glucose reabsorption (90%) from the glomerular filtrate
overexpressed in those with T2DM
What is the MOA of SGLT2 inhibitors?
inhibit SGLT2, thereby decreasing the reabsorption of glucose, and increasing urinary glucose excretion
insulin-independent action
True or false: hypoglycemia occurs with SGLT2 inhibitors
false
they have no insulin stimulation
What are the effects of SGLT2 inhibitors on blood glucose?
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)
What is required for SGLT2 inhibitors to work?
functioning nephrons
hence BG lowering ability declines with decreased renal function
What is the effects of SGLT2 inhibitors on weight?
~2-3kg average weight loss
occurs through a loss of 60-80g/d glucose in urine
plateaus at 26 weeks; is sustained
What is the dosing of SGLT2 inhibitors?
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
What occurs to kidney function upon initiating an SGLT2 inhibitor?
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
What are the adverse effects of SGLT2 inhibitors?
most common:
-increased urination
-increased thirst
-mycotic genital infections (females>males, usually once)
less common/rare:
-UTIs (recently found no increased risk)
-DKA
What are the effects of SGLT2 inhibitors on lipids and blood pressure?
lipids (~5%):
-mild increase in LDL and HDL
-decrease in TGs
blood pressure:
-mild decrease in SBP and DBP (3-5mmHg and 2mmHg)
What is the management and prevention of genital mycotic infections for a patient on an SGLT2 inhibitor?
pee, rinse, wipe
What are some contraindications and precautions with SGLT2 inhibitors?
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
What are drug interactions with SGLT2 inhibitors?
concomitant use with diuretics may increase risk of hypovolemia and hypotension
Does canagliflozin increase risk of amputations?
probably not
caution in history of amputation, diabetic neuropathy, PAD, diabetic foot ulcers
Does canagliflozin increase risk of bone fracture?
no increased risk in those not at risk to begin with
caution in older adults with high fracture risk, fall risk, and hydration status
What is Fourniers gangrene?
pain, swelling, tenderness in genital region
cases reported with canagliflozin but not in mass
Which SGLT2 inhibitor is currently covered under the SK formulary for treatment of Class II and III heart failure?
dapagliflozin
Summarize the cardio renal benefits of SGLT2 inhibitors.
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
What are the premixed insulins available for T2DM?
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)
When should premix regular be injected? When should premix analogues be injected?
premix regular: 30-45 minutes before starting a meal
premix analogues: 15 minutes before or after a meal
What are the barriers to insulin?
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
What are the options when initiating insulin with a T2DM patient?
- 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 - basal and bolus insulin
- biphasic (premixed) insulin
How is basal insulin titrated in T2DM?
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
Why is it preferred to initiate with basal insulin in T2DM?
simplicity
minimization of weight gain and hypoglycemia
keeping oral meds on board helps with insulin sensitization
What is the ceiling effect of basal insulin?
0.5U/kg/d
What should we start to consider thinking that basal insulin has hit its ceiling effect?
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
How is iGlarLixi dosed?
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
How is IDegLira dosed?
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
How do we dose bolus insulin in T2DM?
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
Describe how to choose therapy for T2DM.
see slide 31 slide deck 5
Describe how to adjust or advance therapy in T2DM when A1C is not at target and/or change in clinical status.
see slide 32 slide deck 5
What should be taken into consideration when choosing a second line drug for T2DM?
clinical CV disease?
hypoglycemia
affect on weight
renal function
degree of hyperglycemia
other comorbidities (i.e. heart failure)
cost
patient preference
What is a new anti-hyperglycemic that has been approved by Health Canada in November 2022?
tirzepatide
What is the MOA of tirzepatide?
GIP and GLP1 dual agonist
-enhances secretion of insulin in response to food and reduces
glucagon (in a glucose dependent manner)
What is the indication of tirzepatide?
adults with T2DM
What are the adverse effects of tirzepatide?
nausea
diarrhea
vomiting
also dyspepsia, constipation, abdominal pain
hypo: increased risk when added to basal insulin/SU
What are the effects of tirzepatide on heart rate, blood pressure, and weight?
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
What are some storage and injection tips for terzepatide?
inject to abdomen, thigh, upper arm (rotate sites)
store in fridge: can store unrefrigerated for up to 21d
Can dapagliflozin, liraglutide, or empagliflozin be used in T1DM?
longer-term results on safety and efficacy are needed before approval beyond T2DM
What is the traditional treatment strategy in T2DM?
diagnosis–>lifestyle–>metformin–>other oral agents–>insulin
typically treat to fail
What is an alternative treatment strategy in T2DM?
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
What is the A1C target pre-pregnancy? What about during pregnancy?
pre-pregnancy: <7% (ideally <6.5% if safe)
pregnancy: <6.5% (6.1% if possible)
What are the FBG and 2hr PPG goals in pregnancy?
FBG <5.3mmol/L
2hr PPG <6.7mmol/L
What does poor controlled diabetes increase the risk of during pregnancy?
miscarriage
stillborn
malformations
When should diabetic women see an ophthalmologist during pregnancy?
before conception, 1st trimester, prn during pregnancy and within 1st year post-partum
What are some potential embryopathic meds?
ACEI/ARB
statins
What can be used for therapy of T1DM during pregnancy? What about T2DM?
T1DM: insulin
T2DM: can continue metformin, glyburide, or insulin
What is the DOC for diabetes (T1 and T2) once pregnancy occurs?
insulin
-metformin and then glyburide may be considered as
alternatives for those women unwilling to use insulin
What is first line therapy for gestational diabetes?
diet and exercise
-if dont achieve glycemic targets within 2wks–>pharmacotherapy
nutrition counseling is important
What is second line therapy for gestational diabetes?
insulin
alternatives: metformin and glyburide
When should women who experienced gestational diabetes be re-screened postpartum?
6wks to 6 months postpartum to see if glycemia is resolved
How long is breastfeeding encouraged to be done to reduce the risk of developing diabetes for both mother and child?
4 months
Does the excretion of insulin through breast milk pose a risk to the infant?
no because its degraded in the GIT before reaching systemic circulation
Why is diabetes more complicated with children?
psychological risks
eating disorders
insulin omission
need access to a dietician
smoking cessation
contraception
What is the treatment of T1DM in children?
whenever possible; intensive insulin (MDI or CSII)
What are the targets for A1C, FPG, 2hr PPG in T1 children?
A1C: <7 or 7.5% for all children <18yo
FPG: 4-8mmol/L
2hr PPG: 5-10mmol/L
What are the pharmacologic options for TD2M in children and adolescents?
metformin: 1st line
metformin and basal insulin if more marked hyperglycemia
metformin + liraglutide: FDA approved >10yrs
Which anti-hyperglycemic drugs should we limit the use of in elderly?
SU
TZD
choose DPP4i over SU
Which type of insulin is preferred for an elderly T2 diabetic?
basal
