Managing Type 2 Diabetes: Moving beyond Metformin and ...
Transcript of Managing Type 2 Diabetes: Moving beyond Metformin and ...
Managing Type 2 Diabetes:
Moving beyond Metformin and
Glipizide
TANYA MUNGER DNP, FNP-BC, AP-PMN, CCHP
Disclosures
Speakers Bureau for Novo Nordisk
Speakers Bureau for Dexcom
Presentation will include brand name medications and technology
No off label discussions
Presentation will include medications in clinical trial
Diabetes Management Goals
A1c <6.5%-8%: depending on age, duration of Dx, and co-morbid
conditions
Reducing CV risk
Weight reduction
Minimizing hypoglycemia
Limitations of A1c
1. May underestimate or overestimate an individual’s average glucose (example: A1C of 7% could represent a range between 123 -185 mg/dL)
2. Does not indicate the extent or timing of hypoglycemia or hyperglycemia
3. Does not reveal glycemic variability
4. Limited utility for insulin dosing decisions
5. Unreliable in patients with hemolytic anemia, hemoglobinopathies, or iron deficiency
6. Underestimates in those with end stage kidney disease or during pregnancy
Nathan DM et al. Diabetes Care. 2008;31(8):1473-1478
A1c% mg/dL 95% CI
5 97 76-120
6 126 100-152
7 154 123-185
8 183 147-217
9 212 170-249
10 240 193-282
11 269 217-314
12 298 240-347
Oral Agents and Non Insulin
Injectables
– Biguanides
– Dopamine-2 agonists
– Bile acid sequestrants
– GLP-1 receptor agonists
– Amylinomimetics
– Sulfonylureas
– Thiazolidinediones
– Meglitinides
– Alpha-glucosidase
inhibitors
– DPP-4 inhibitors
– SGLT-2 inhibitors
Biguanides-Metformin (Glucophage)
Anticipated A1c reduction: 1-2%
Targets insulin resistance
Reduces hepatic glucose production and intestinal glucose absorption
Fasting and post prandial
Hypoglycemic risk: minimal
GI side effects-titrate slowly
Weight neutral/weight loss
Biguanides-Metformin
(Glucophage)
Consider discontinuation eGFR <45, absolute discontinuation eGFR <30
Rare risk of lactic acidosis
Long term use associated with B12 deficiency due to altered absorption
90% excreted via kidneys
Discontinue before iodine contrast imaging, restart after 48 hrs
500-1000 mg BID, max 2550 mg/day (extended release intended for once
daily use)
Sulfonylurea
(Glipizide, Glyburide, Glimepiride)
A1c reduction: 1-2%
Fasting & Postprandial
Increases insulin release from beta cells
Hypoglycemic risk: moderate/severe
Less effective in elderly or those with long duration of DM due to failing beta cell function
Weight gain
Sulfonylurea Dosing
Glyburide
• 1.25-20 mg/day qd-BID
• Max 20 mg/day
• Take with meals
Glimeperide
• 1-4 mg/day
• Max 8 mg/day
• Take with first main meal
Glipizide
• 2.5-20 mg qd-BID Max
• Max 40 mg/day or 20 mg/day ER
• 30 min before meals
• do not crush/chew
• Extended release preparations are
intended for once daily use
DDP4 Inhibitors(Januvia, Onlyza, Nessina, Tradjenta)
Works on hormones in the gut, increasing insulin production
Inhibits DPP-4 enzyme in the GI tract that breaks down GLP-1
resulting in ↑ endogenous GLP-1
Prolonged endogenous GLP-1 action: decrease liver glucose
production, enhances insulin & amylin secretion in pancreas
Weight neutral
A1c lowering: 0.5-0.8%
Post prandial benefits
Nasopharyngitis, URI
DPP4 Inhibitor Dosing
Sitagliptin (Januvia®)
25 mg, 50 mg, and 100 mg
Once-daily dosing
Saxagliptin (Onglyza® )
2.5 mg and 5 mg
Once-daily dosing
Linagliptin (Tradjenta®)
Once-daily dosing
5 mg
Alogliptin (Nesina®)
Once-daily dosing
6.25mg, 12.5mg,25 mg
Cardiovascular Risk Reduction &
Weight Reduction
GLP-1 Receptor Agonists:Exenatide (Bydureon/Byetta), Liraglutide (Victoza),
Dulaglutide (Trulicity), Semaglutide (Ozempic,
Rybelsus)
Ozempic, Trulicity, Rybelsus, Victoza, Byetta, Bydureon
Weight reduction
CV risk reduction
A1c reduction: 1-2%
SE: nausea, fullness, bloating, constipation
Contraindicated in pts with Hx of MTC and pancreatitis
No renal or hepatic dose adjustments
GLP-1 Receptor Agonist Dosing
Liraglutide (Victoza®) • 0.6 mg, 1.2 mg, & 1.8 mg • Once-daily
dosing
Exenatide (Bydureon®) • 2 mg • Once-weekly dosing; (Byetta®) 5 & 10 mcg/BID (short acting)
Semaglutide (Ozempic®) •0.25-1mg • Once weekly
Semaglutide (Rybelsus®) 3 mg, 7 mg, 14 mg, once daily, oral
Dulaglutide (Trulicity®) • 0.75mg & 1.5mg, 3 mg, 4.5 mg • Once-weekly dosing
Rybelsus (Semaglutide)
Oral GLP1 with special coating
Once daily
No more than 4 ounces of water
No food, beverages, or medications for 30 mins
3 mg, 7 mg, 14 mg
No adjustments for age, hepatic or renal disease
Wegovy (Semaglutide)
GLP-1 indicated for weight loss
Auto injector pens
Once weekly dosing
Dosing: 0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg
Titrate upward to 2.4 mg weekly
Sodium Glucose Transport Inhibitors
(SGLT2)
Farxiga, Jardiance, Steglatro, Invokanna
Once daily oral
Removes glucose from blood stream via kidneys/urine
A1c Reduction: 1%
BP lowering
Weight reduction
CV risk reduction
Slows progression of CKD (Farxiga)
Decreases readmission in CHF (Farxiga)
SGLT2 Inhibitor Dosing
Dapagliflozin Farxiga
5-10 mg once daily
Empagliflozin Jardiance
10-25 mg once daily
Risk of UTI and yeast infection in groin
Drink plenty of water
Keep groin area clean and dry
Invokana-increased amputation risk
Canagliflozin Invokana
100-300 mg once daily
Ertugliflozin Steglatro
5-15 mg once daily
Farxiga (Dapagliflozin)
FDA labeling for reducing CV risk, progression of CKD (pts with DM
and without) and hospital admissions fro HF
GFR for glucose management: 45
GFR for reducing progression of CKD: 25
Once on the medication can remain on until dialysis
Voucher for 30 days free
Jardiance (Empagliflozin)
FDA indicated to reduce CV risk and hospital admissions for HF
Kidney data available, CKD labeling in the future
GFR for glucose lowering: 30
GFR for HF: 20
Voucher Programs
Trulicity
Ozempic
Farxiga
Bydureon
Vouchers are for a free 30 day supply
Jardiance: 14 day free voucher
Not a coupon or co-pay card
Pharmaceutical rep needs to have contact with provider or even
clinic manager
History of Insulin
Starvation diets
400-500 calories daily
First insulin bovine-many allergies
First injection Jan 1922
Diabetes no longer a death
sentence, now a manageable
chronic condition
History of Insulin
First insulin U-20 the U-50
Biosynthetic commercially
available 1980’s
Lantus/Levemir year 2000
Insulin Therapy
Spectrum of Options
Conventional
Insulin
Therapy
Insulin
Pump
Therapy
Intensive
Insulin
Therapy
Sensor
Augmented
Pumps
ArtificialPancreas Technology
Indications for Insulin Therapy in
Type 2 Diabetes
Significant hyperglycemia at dx
Hyperglycemia despite being on effective doses of orals
Intolerance of orals due to side effects
Renal or hepatic disease
Surgery, pregnancy, hospitalization (acute injury, infection, stress)
Unable to afford oral medications
Starting Basal Insulin
Safe to start 10 units once daily (AM or PM)
Titrate upward by 2 units daily until FBS is at 150
Can increase by 5-10 units weekly as needed
Once pt reaches 50-60 units daily consider meal time coverage
Titration of Insulin
Titrate upwards by 3 units every 2-3 days until FBS at goal
FBS >180: add 6 units basal (20% TDD)
FBS 141-180 add 4units basal (10% TDD)
FBS 100-120 add 1 unit (1 unit)
FBS 80 or less subtract 2 units (10-20%)
Meal Time Insulin
May consider a GLP1 first
Discontinue sulfonylurea to avoid hypoglycemia
Continue basal insulin
Begin prandial insulin with largest meal
Start with 10% of basal dose or 5 units
If not at goal can add dose with 2nd and/or 3rd meal
Use 15 mins before eating (R is 30 mins)
Avoid complicated sliding scales
Basal Bolus With All Meals
Begin prandial insulin before each meal
50% basal & 50% prandial(TDD 0.3-0.5 units/kg)
Start 50% of TDD in 3 doses before meals
Concentrated Insulin
When daily insulin requirements are in excess of 200 units/day, the volume of U-100 injected insulin may become an issue
Physically too large for a single SC administration
Multiple injections are required to deliver a single dose
Increased injections may lead to compliance issues and poor glycemic control
Discomfort
Unpredictable absorption (rate-limiting step in insulin activity)
Concentrated Glargine U-300
U-300 insulin glargine offers a smaller depot surface area, leading to a
reduced rate of absorption
Provides flatter and prolonged pharmacokinetic and pharmacodynamic
profiles and more consistency compared to U100 glargine
Half-life is ~23 hours, blood glucose control beyond 24 hrs
Steady state in 4 days
Duration of action ≤36 hours
FDA approved February 25, 2015 (Toujeo®)
Degludec U-100 & U-200
Available only as FlexTouch pens
• U-200: 600 units/pen, max 160 units/inj
• U-100: 300 units/pen, max 80 units/inj
• Duration of action >42 hours
• Half-life ~25 hours
• Detectable for at least 5 days
• Steady state in 3-4 days
Humulin R U-500 Insulin
Patients on high dose, >200 units daily, 5xs potent
Onset 30 mins, duration up to 24 hrs
Time action characteristics reflecting prandial & basal activity
U-500 Kwick Pen: can deliver 300 units in a single injection, dials in 5 unit
increments, 1500 units in each pen
Still comes in vial but requires specific syringe
Walmart Insulin
Novolin N: 12 hour acting, twice daily dosing
Novolin R: meal time insulin, 30 mins before meal
Novolin 70/30 or 75/25; Split mixed, twice daily dosing
Vial: $25, Box of pens: $40
Financial Assistance
$99 per month programs for insulin
Insulin and non insulins at no cost
Lilly: lillycares.com (Humalog, Basaglar, U-500)
Novo: Novocare.com (Tresiba, Levemir, Novolog, Fiasp)
Sanofi: sanofipatientconnection.com (Lantus, Toujeo, Admelog,
Apidra)
What’s Next?
Clinical Trials
Clinicaltrials.gov
Medications in phase 3 trials
Local pharmaceutical reps can not discuss medications that are in
trial
Can only discuss FDA approved medications
Tirzepatide
GLP1/GIP dual therapy (new class/category)
Both GIP and GLP-1 are hormones secreted by the gut in response
to nutrients. They are responsible for the incretin effect, which enhances the secretion of insulin after a meal
GIP also impacts weight related mechanisms
Once weekly injectable
Dosing: 5 mg, 10 mg, 15 mg
Promising data in regards to A1c and weight reduction
Insulin Icodec
Once weekly long acting insulin
Terminal half life of 196 hours
Primary end point: Percent of time in range monitored with CGM
Secondary endpoint: A1c reduction, hypoglycemia, and adverse
events
Continuous Glucose Monitoring
Dexcom, Libre & Libre 2
No finger sticks, data sharing with HCPs remotely
Monitor BS as frequently as desired
Audible alarms (Dexcom, Libre 2)
Trending arrows showing direction of BS
Can use receiver or smart phone if compatible
Share data with family
Libre Freestyle Continuous Glucose
Sensor-Intermittent Scan
Dexcom G6 Continuous Glucose
Sensor-Real Time (iCGM)
CGM Insurance Requirements
Type 1 DM or Type 2 DM on intensive insulin therapy (MDI/pump)
Testing BS 4 times daily (Medicare dropped this 7/18/2021)
Meal time insulin and self adjusting doses or sliding scale
This must all be in you visit note and the ICD-10
Will include inhaled insulin (Afrezza)
Community Walgreens
Dexcom Prescribing
Receiver: 1 unit every 5 years
Transmitter: 1 unit every 3 months
Sensors: 3 sensors per month
Libre, Libre 2
Receiver-1 every 5 years
Sensors-2 per month
Near Future of CGM
Companion Medical InPen
Reusable pen for short acting, meal time insulin
Humalog or Novolog cartridge
Bolus calculator
Real time insulin-on-board tracking
Reminders to avoid missed meal doses
Insulin temp monitor
InPen app receives CGM data (24 hr avg/summary trends)
Auto texts with each interaction (up to 5 recipients)
InPen Insights Report
InPen Requirements
Must be able to count carbohydrates
Must be monitoring blood glucose at least 3 times daily
If able to master InPen it is a smother transition to a pump
Meet with CDE to calculate I:C ratio & ISF/Correction
Must down load application
Share Insights Report via MyChart
Summary
Consider medications that offer CV risk reduction and weight
reduction
Consider medications that slow progression of CKD
Do not hesitate to start long acting insulin 10 units daily
Consider CGM in patients who qualify