14/15 - DM Injectables Flashcards
LipoAtrophy
thought to be due to insulin antibodies
or allergic-type reactions w/ destruction of FAT @ site of injection
Levemir Vial / 300-Unit Flexpen
Dosed / Onset / Duration
MoA
Long-Acting Insulin Detemir
Dose QD or BID
BID benefits patients with elevated PRE-Dinner BG
Onset = 1 hour, relatively FLAT peak
monomers are 98-99% albumin bound, delays the distribution into target tissues.
Initiating RX:
Mixed Insulin Regimen
Premixed Insulins like 70% NPH (LA) + 30% Regular (SA)
- Estimate total insulin needed per day:
- 0.4 - 0.5 units/kg/day (same as MDI)
-
Before breakfast:
- 2/3 of total daily dose before breakfast
-
Before Dinner
- 1/3 of total daily dose before dinner
How are Insulin products CHARACTERIZED by?
All insulin products contain only ACTIVE insulin peptide
Onset
Duration of Action
Strength
Source
Analog
insulin that had AA within molecule modified for physiochemical / PK advantages
Weight Gain from Insulin
In comparison to Metformin & SulfonylUreas
Insulin > Sulfonylurea > metformin (no weight gain)
When to consider Dual Therapy for T2DM?
A1C > 9%
Lifestyle management + Metformin + ADDITIONAL AGENT
Diabetes KetoAcidosis
DKA
Criteria / Physical Findings
Typically seen in T1DM, rare in T2DM
- Glucose > 250mg/d
- Presence of serum ketones, serum pH < 7.3
- Anion gap >10, plasma bicarb <18 meq/I
- S/S of:
- polyuria / polydipsia / N&V / Coma
- dehydration, hypotention + tachycardia
- fruity breath from ketones
- MORE Respirations
Insulin Sensitivity Factor
ISF
(correction Factor)
“1800 Rule” for RAPID-Acting Insulin
“1500 Rule”** for **short-acting insulin
- Determines how much
- Glucose is lowered by 1 unit of insulin
- Based on ALL THE UNITS of insulin that person takes in 1 day
- Ex. Used 54 units / day
- 1800 / 54 units = 33.33
- BG will be lowered by ~33mg/dL
- for every 1 unit of humalog
- BG will be lowered by ~33mg/dL
- 1800 / 54 units = 33.33
Insulin Release Kinetics
2 Phase Kinetics - difficult to replicate when dosing insulin
Acute 1st Phase - lasts a few minutes (0-10), high peak
Sustained Second Phase - SECRETION, persists for the duration of the high-glucose stimulus (10-80+)
When to consider Injectable Therapy?
A1C > 10%
BG > 300mg/dl
or patient is markedly symptomatic
Fast-Acting Analog
Aspart (Fiasp) / Novo Nordisk
Dosed / Onset / Duration
Newly approved formulation of Novolog
+ niacinamide -> increase speed of initial absorption
+ L-arginine to boost stability
Dosed at the BEGINNING OF A MEAL or within
20 MIN AFTER STARTING A MEAL
Advantages & Disadvantages
of MDI Insulin Regimen
Basal = LA (Lantus or Levemir)
Bolus = RA (LAG - Humalog/Novolog)
-
Adv:
- __Offers FLEXIBILITY in meal size & timing
- best MIMICS endogeneous insulin production
- Disadv:
- Required multiple injections
- have to test BG often
Insulin Therapy for
T1DM vs T2DM
T1DM
- almost NO insulin secretion*
- will be dependent on insulin for the rest of their lives*
T2DM** - **lower A1C >2%
most effective in lowering hyperglycemia,
Initiate AFTER optimized ORAL therapy or failure to achieve target goals
Types of Premixed Insulins
•Humalog Mix 50/50
•Humalog Mix 75/25
•NovoLog Mix 70/30
•Humulin 70/30
•Novolin 70/30
Types of Short-Acting (Regular) Insulins
+ Concentrated Regular Insulin
Considered Bolus / R = Regular
Humulin R
Humulin R U-500
Novoin R
Sliding Scale Insulin
SSI
Reactive, not PROACTIVE
NOT RECOMMENDED TYPICALLY, only seen in Hospital care
- Does not provide physiologic insulin needs:
- “Chasing” of BG
- supplementation / correction scale
Types of Long-Acting Insulins
Glargine (Lantus)
Detemir (Levemir)
- can not be mixed*
- considered Basal*
Resolving GDM
gestational diabetes
Insulin -> reduction in fetal moridities
similar efficacy among VARIOUS insulin regimens
TARGET A1C = 6-6.5%
A1C target is *LOWER* due to INCREASED RBC turnover
FPG <95 mg/dl
1hr PPG < 140mg/dl or 2hr PPG < 120mg/dl
HHS
Hyperglycemic Hyperosmolar State
Similar to DKA except patients are
NOT acidotic
Fluid Deficit is GREAT
common in T2DM, mortality rate is 50%
Treatment is the SAME as DKA
Insulin to Carbohydrate Ratio
ICR
“Rule of 500”
T1DM on average = 1unit:10g
T2DM on average = 1unit:15g
-
Divide 500 by the TDD of Insulin
- Ex. TDD = 54 units
- 500 / 54units = ~10g
- therefore - 1 unit of insulin per 10g of carbs
- 500 / 54units = ~10g
- Ex. TDD = 54 units
-
Each person has their OWN ICR
- used to figure out meal BOLUS
Premixed Insulin Regimen Effects
of PM=EVENING- Short-Acting (Bolus) insulin
major action time & effect reflected?
Major action is between Supper & Bedtime
Effect is reflected in the Bedtime BG levels
Types of Ultra Long-Acting Insulin
Glargine
( Toujeo U-300 )
Degludec
(Tresiba U-100 / U-200)
Sick Day Management
MUST FOR T1DM
-
Continue insulin therapy 50-100% of basic insulin dose
- even when NOT eating
- or presence of N/V
-
Test BG & Ketone MORE frequently
- Q3-4
- may need to supplement insulin
-
FLUID REPLACEMENT
- very important
- jello / chicken broth / soup
Treatment of DKA
FLUID REPLACEMENT
Insulin supplement
Potassium Replacement
DM for Special Populations
Older Adults (Elderly)
-
Need to consider risks
- hypoglycemia
- comorbiditiesm, microvascular disease + CVD
- dexterity / self-care
- Nutrition
- Social support / mental status / life expectency
- FALLS RISK
- Decline in renal function needs to be considered
3 Primary Physiological Actions
of Insulin
INCREASE glucose disposal
- Decrease* hepatic glucose production
- Supresses* ketogenesis
Intermediate-Acting Insulin / NPH
Humulin N / Novolin N
Dosed / Onset / Duration
DOSED BID
Onset = 1-3 hours
LONG Duration = 12-16 hours
Prominent Peak = 8 HOURS (4-10 hours)
–> risk of hypoglycemia @ time of PEAK
Weight GAIN
Major factor in limiting insulin adjustments
Basal Insulin / (Ultra) Long-Acting Insulin
Glargine / Detemir / Degludec
Dosed / Onset / Duration
Onset & Duration VARIES
between each formulation
MIMICS normal pancreatic basal insulin secretion
Peakless, predictable effects
Reduced risk of nocturnal hypoglycemia
Switching Insulin Products
NPH –> Basal
(Intermediate Acting, -N) –> (Long Acting, Lantus/levemir)
Basal –> NPH
don’t need to know these specifics
QD NPH -> QD Basal (LA)
same dose 1 to 1
BID NPH -> QD Basal (LA)
initiate w/ 80% of TDD
LipoHYPERtrophy
Injection site complication
caused by Many injections into SAME SITE
thick / rubbery scar
avoid by ROTATING INJECTION SITES
use larger injection zone >1cm frome ach
do not reuse needles
Initiating RX:
Basal + Bolus Regimen
(MDI = multiple dose insulin, Regimen)
LA (Lantus or Levemir) + RA (LAG - Humalog/Novolog)
- Start insulin based on WEIGHT
- 0.4 - 0.5 units/kg/day
- BOLUS (LAG)
-
20% of starting dose (calculated above) @ each meal
- 20% x Dose TID-AC
-
20% of starting dose (calculated above) @ each meal
-
Basal (NPH - glargine/detemir/degludec)
- 40% of starting dose @ bedtime
- 40% x Dose QHS
- 40% of starting dose @ bedtime
Premixed Insulin Regimen Effects
of AM-_Intermediate-Acting (Basal)_ insulin
major action time & effect reflected?
Major action is between BREAKFAST & Supper
Effect is reflected in the Pre-SUPPER BG levels
Dosage Adjustment for
Basal + Bolus MDI Regiment
Basal = LA (Lantus or Levemir)
Morning glucose reading, PRE meal
Bolus = RA (LAG - Humalog/Novolog)
POSTPRANDIAL
What differs between Insulin Preparations
There is NO DIFFERENCE IN EFFICACY between newer & older formulations
its the PHARMACOKINETIC PROFILES that are different
HIGHER DOSE for T2DM vs T1DM
Adjusted based on BG results
MAX DOSE = Based on effectively lowering BG
Premixed Insulin Regimen Effects
of AM-Short-Acting (Bolus) insulin
major action time & effect reflected?
Major action is between BREAKFAST & LUNCH
Effect is reflected in the Pre-Lunch BG Levels
Lantus, SolaSTAR Pen
Dosed / Onset / Duration
MoA
Long-Acting Insulin Glargine
Administered ONCE A DAY & should be SAME TIME EACH DAY
no pronounced peak, 1 hour Onset
Injection of acidic solution (pH 4.0) –> precipitation of Glargine in subQ tissue (pH 7.4) –> slow dissolution of glargine from hexamers
GDM
Gestational DM
Any Degree of GLUCOSE INTOLERANCE
with onset or first recognition during pregnancy
4-5% of ALL pregnancies
Increased Risk of Macrosomia (birth weight)
& Birth Complications (spinal bifida, birth defect)
Neonatal hypoglycemia
Maternal Hypertention
Types of Rapid-Acting Insulins
Considered BOLUS
L L A G
Lispro (Humalog U-100 / U-200)
Lispro (Admelog)
Aspart (Novolog)
Glulisine (Apidra)
Inhaled AFREZZA
Concept of Basal + Bolus Insulin
LA (Lantus or Levemir) + RA (LAG - Humalog/Novolog)
-
Basal Insulin = Long Acting
- Supresses glucose production between meals & overnight
- nearly consistant levels
- covers 40-50% of daily needs
-
BOLUS INSULIN = Rapid acting
- for mealtime/prandial
- limits hyperglycemia AFTER meals
- immediate rise / peak @ 1 hour
- ~10-20% of total daily insulin req @ each meal
*
Toujeo (U-300)
Dosed / Onset / Duration
MoA
ULTRA Long-Acting Insulin Glargine
Dose = QD @ same time each day
LATE Onset: 6 hours
Duration = 36 Hours
Same maker as LANTUS & smaller volume
Disadvantages of Insulin
HYPOGLYCEMIA / WEIGHT GAIN
Pt / provider RELUCTANCE
Training requirements / Injectable
(pulmonary toxicitiy_
ICR vs ISF
(Insulin to Carb ratio) vs (Insulin Sensitivity Factor
ICR
Bolus insulin,
Determines how many grams of carbs are convered by 1 unit of insulin
Units : Carbs
ISF
Used in correction or supplementation
of insulin doses when glucose levels are too high/low BEFORE meals
___ mg/dl for every 1 unit of insulin
Premixed Insulin Regimen Effects
of PM=Evening -Intermediate-Acting (Bolus) insulin
major action time & effect reflected?
Effect is reflected in the NEXT MORNING BG Reading
Tresiba (U-100/U-200)
Dosed / Onset / Duration
MoA
ULTRA Long-Acting Insulin Degludec
Duration ~42 hours
Onset = 90 minutes
no peak, lower risk of hypogllycemia
Allows for flexibility in dosing, especially with a MISS
slow release from subQ depot
Rapid - Acting Insulin
Lispro / Aspart / Glulisine
Dosed / Onset / Duration
Compared to Regular/Short-Acting,
ACTION is faster / PEAK is HIGHER / dissapears faster
Convenient, take immediately prior to means
Onset = 15 Minutes
Duration = 3-5 Hours
Resolution & Prevention
of DKA
- Resolution:
- Patient is clinically stable
- BG < 200mg/dl
- Serum bicarbonate > 18 meq/l
- Venus pH >7.3
-
Prevention:
- educate patient about precipitating factors
- sick day management
Options after Initiating Basal Insulin
A1C not Contolled
3
Combination Injectable Therapy
- Add 1 Rapid-Acting Insulin before largest meal
-
4 units or 0.1 units/kg
- (or 10% basal dose)
-
4 units or 0.1 units/kg
- Add GLP-1 RA
- possibly not tolerated for A1C target
-
Change to premixed insulin BID (b4 breakfast + supper
- 2/3 AM –> 1/3PM
Advantages of Pre-MIXED Insulin
Increase Glucose Disposal
- Decrease hepatic glucose production*
- Supressess Ketogenesis*
Mixing with other formulation in the same syringe prior to injection
is NOT RECOMMENDED
Dawn Effect
AE of Insulin
Elevated FBG due to
early morning CORTISOL & EPInephrine Release
Toujeo (U-300)
Other stuff
ULTRA Long-Acting Insulin Glargine
INITIATION in T1DM, glucose lowering effect may take up to 5 days & first few doses may NOT be sufficient to cover needs
After switch, temporary RISE in FPG in first WEEKS of therapy
Titrate no more frequently than q3-4 days, to minimize hypoglycemia risk
DM for Special Populations
Children & Adolescents
-
METFORMIN is the ONLY FDA approved ORAL agent
- 10-16 years of age
- unfortunately, monotherapy is POOR in many adolescents
- Sulfonylureas are also commonly used
- INSULIN continues to be the standard of care
-
when glycemic goals cant be reached with
- metformin/sulfonylureas
S/Sx of hypoglycemia
Shaking / Sweating / weakness fatigue
Fast Heartbeat / Anxious / Dizziness / Irritable
Impaired VISION / HEADACHE / HUNGER
Somogyi Phenomenon
AE of INSULIN
Nocturnal hypoglycemia followed by REBOUND HYPERglycemia
Treating GDM
Gestational Diabetes
Lifestyle modification is ESSENTIAL
restrict calories / carbs / small meals many times thru day
INSULIN is preffered medication, does not cross placenta
metformin + glyburide may be used but –> crosses placenta
Advantages of Insulin
NEARLY Universal Response
Theoretically Unlimited Efficacy
- Decrease microvascular risk*
- (UKPDS)*
Basaglar KwikPen
First approved “FOLLOW-ON” insulin
LONG-acting Glargine
biologically similar to LANTUS, same protein sequence & effects
Humulin R U-500
Used for who? / Testing / onset+duration
CONCENTRATED human insulin, for those who require >200 units of insulin /day
need proper training / special syringe
BID/TID 30 min prior to meal
onset = ~15 min
peak = 4-8 hours
duration = ~21 hours
Regular (Short-Acting) Insulin
Humulin-R / Novolin-R
Dosed / Onset / Duration
- inconvenient administration*: 20-40 minutes PRIOR to meals
- Slow Onset =* 30-60 min
LONG duration = 5-8 hours
peak is @ 2-4 hours
multiple-injection regimen, potential for late PP-hypoglycemia
- caution with PP-exercise*,
- SLOW to correct hyperglycemia*
Hypoglycemia
Glucose Level / 2 categories of Symptoms
Glucose < 70mg/dl
2-3x HIGHER RISK when needed to intensively regimen dose
Adrenergic ( epi secretion )
sweating / tremor / tacyCardia / anxiety / hunger
Neuroglycemic ( CNS dysfunction )
dizziness / headache / blunted mental activity / loss of fine motor skill / confusion / abnormal behaviro / convulsion / loss of conciousness
Insulin Storage & Disposal
Avoid Heat / Light / Freezing
Store UNOPENED products in FRIDGE
Pen can be kept at room temperature, keep storage in fridge
check exp date & appearance
Types of Fast-Acting Insulin
ASPART
(Fiasp)
Novo Nordisk
new formulation of Novolog
Afrezza
Rapid-Acting Insulin
Human Insulin INHALATION powder
Oral inhalation @ beginning of each meal
- many NEGATIVES:*
- need to Assess Lung Function + Spirometry (FEV1)*
- Contraindicated in pts w/ Chronic Lung Disease*
Types of Intermediate-Acting Insulin / NPH
(NPH = isophane Insulin, neural protamine Hagedorn) N = NPH
Only one that can be MIXED,
also considered BASAL
Humulin N
Novolin N
Initiation of Injectable Therapy
Initiate BASAL INSULIN
start: 10 U/day or 0.1-0.2U/kg/day
* adjust 10-15% or 2-4 units QD/BID to reach FBG target*
usually with Metformin +/- *noninsulin agent*
Adverse Effects
of Insulin
hypoglycemia / weight GAIN
LipoAtrophy & LipoHYPERtrophy
Somogyi Phenomenon
Dawn Effect