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