Basal-Bolus Insulin Therapy

Veronica Brady, PhD, FNP-BC, BC-ADM, CDEECHO

January 18 2018

Terminology No longer using the term “diabetic.” Diabetes does not define people. People with diabetes are individuals with

diabetes, not “diabetics.” “Diabetic” will continue to be used related to

complications, e.g., “diabetic retinopathy.”

ADA, Diabetes Care,2016;

Objectives Review insulin therapy

Older Newer Latest

Discuss starting Insulin Discuss adjusting Insulin

The Case of AB (Diagnosis) AB is a 34 year old male who presents to the

office with complains of worsening vison, nocturia, nightmares, and extreme thirst. MH is non-contributory SH-tonsillectomy, appendectomy FH is significant for DM in his father and paternal

grandmother, CAD in father with stents at age 54, HTN in his mother

SH is significant for smoking ½ ppdx20 years, occasional ETOH, +marijuana. He is single and works in a packing warehouse.

The Case of AB cont Vitals-weight 234#, BMI 35, BP 149/87, P89 A1c in office today 9.3% PE-

HEENT-WNL Cardio-RRR Lungs-CTA Abdomen-obese LE-trace edema, ++DP pulses, Feet-+sensation to 10gram monofilament

The Case of AB (year 1) AB returns to your office 3 months after

diagnosis. He has been to DSME classes. He states that he has attempted to change his eating habits (less fatty foods, fewer sweets, etc.) and tried to exercise (he walks “a lot” at work and lifts heavy boxes).

He weight today is 230#, BP: 140/90 Labs: chol-204mg/dL, LDL 112mg/dL, Cr-1.3,

microalb-10, TSH 2.5, A1c-8%

The Case of AB (year 3) It has been 3 years since diagnosis . You

have seen AB in clinic every 3-4 months in the interim since his first visit. In that time you have increased his Metformin to 1gm BID, started glimiperide 4mg BID and put him on max dose of Invokana 300mg/d. He is also on a statin and an ACE.

He has managed to lose 12# and keep it off. He reports mild nausea, urinary frequency and some numbness and tingling of his feet.

The Case of AB (year 3) Labs: chol-157mg/dL, LDL 95mg/dL, urine

microalb-25, A1c-8.8% PE: unremarkable

"There are two times to start insulin for type 2 diabetes," "The first is any time blood sugar is significantly out of control and a patient has symptoms,“."In these cases, the need for insulin may be short-term. “The second time is when type 2 diabetes has progressed over many years and the pancreas can no longer make enough insulin to respond to other diabetes medications."

Alaleh Mazhari, DO Loyola University Health System

InsulinA peptide hormone composed of 51 amino acids secreted by pancreatic beta cells

Synthesized as preproinsulin, then cleaved to proinsulin and stored in secretory granules, which is then cleaved into C-peptide and insulin in the secretory granules

Insulins Rapid Acting Short Acting Intermediate Acting Long Acting Ultra Long Acting

What is the “Best Practice” for Managing Diabetes with Insulin?

Anticipatory, physiologic insulin dosingprescribed as a basal/ bolus insulin regimen

giving the right type of insulin, in the right amount, at the right time, to meet the insulin needs of the patient

Wesorick, et al.

Normal Insulin SecretionBasal: continuous insulin to compensate for liver glucose

Bolus: surge for food 1st phase: rapid rise in serum insulin levels inhibits

glucagon release and therefore inhibits glycogenolysis 2nd phase: to maintain normoglycemia postprandially

Components of Physiologic Insulin Regimen

Basal insulin (detemir, glargine, NPH,degludec) Circulates between feedings Restrains glucose production, and catabolism of stored fuels Defends against ketoacidosis About 50% of daily insulin requirement

Nutritional insulin (aspart, glulisine, lispro, regular) Mimics rapid secretion of insulin in response to feeding Promotes assimilation of ingested nutrients Moderates post-prandial hyperglycemia

OLDER INSULINS

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Rapid Acting InsulinLispro/Humalog Glulisine/ApidraAspart/Novolog

Onset: 15 minutesPeak: 30-90 minutesDuration:3-5 hours

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Short Acting Insulin Regular

Onset: 1 hr Peak: 2-4 hrs Duration: 4-12 hrs

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Intermediate Acting InsulinNPH

Onset: 1.5-4 hrsPeak: 4-12 hrsDuration: up to 24 hrs

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Long Acting InsulinDetemir/LevemirOnset: 0.8-2 hrsPeak: 3.2-9.3 hrsDuration: up to 24 hrs

Glargine/Lantus Onset: 1-2 hrsPeak: peaklessDuration: 24 hrs

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Premixed insulin at breakfast and supper

Humulin 70/30 70% Isophane Suspension (intermediate acting insulin) 30% Regular

Vial: 28 days once in use, Pen: 10 days once in use

Novolin 70/30Relion 70/30

70% Isophane Suspension (intermediate acting insulin) 30% Regular

28 days once in use

Humulin 50/50 50% Isophane Suspension (intermediate acting insulin) 50% Regular

28 days once in use

Humalog Mix 75/25 75% Lispro Protamine Suspension (NPL) (intermediate acting) 25% lispro

Vial: 28 days once in use; Pen 10 days once in use

Humalog Mix 50/50 50% Lispro Protamine Suspension (NPL) (intermediate acting) 50% lispro

Novolog Mix 7030 70% Aspart Protamine Suspension (intermediate acting) 30% aspart

Vial: 28 days once in use; Pen 14 days once in use

Combination Insulins

NEWER INSULINS

RAPID ACTING

Inhaled Insulin Stimulates glucose uptake by skeletal muscle and fat:

inhibits hepatic glucose output

Inhaled Insulin

Onset & peak duration of action Peak 53 minutesDuration 160 minutes

Main Benefits Less hypoglycemia

Common adverse effects Hypoglycemia, cough, throat pain or irritation

Cautious Use Acute bronchospasm reported in patients with asthma and COPD using inhaled insulin

Contraindications Contraindicated in patients with chronic lung disease, smoker, DKA, hypersensitivity to regular human insulin

Afrezza

Afrezza Considerations:

Lung function-no smoking (none within 6 months) Set doses—not possible to get 3 units Amount of insulin needed for each meal Must be at room temp for 10 minutes before use

Humalog U-200 Generic Name- lispro U-200 Brand Name: Humalog U-200 Manufacturer: Eli Lilly Form: analog Delivery: pre-filled pen (600 units) Storage: in use 28 days—do not refridgerate Onset: 15 minutes Peak: 30-90 minutes Duration: 3-5 hours

INTERMEDIATE ACTING

U-500 pens Generic Name-regular U-500 Brand Name: Humulin R U-500 Manufacturer: Eli Lilly Form: human Delivery: 3 ml pen fill (1500 units) Storage- in use do not refrigerate—28 days Onset: 30 minutes Peak: 8 hours Duration: up to 24 hours

U-500 pens Considerations:

Indicated for patients requiring more than 200 units of insulin/day.

Administer 2-3 times a day 30 minutes before meals

Do not mix with other insulins

U-500 Insulin Pharmacologic profile similar to NPH

Useful in patients with: Obesity Immune-mediated insulin resistance Genetic abnormalities of the insulin receptor

U-500 Insulin Pharmacologic profile similar to NPH

Useful in patients with: Obesity Immune-mediated insulin resistance Genetic abnormalities of the insulin receptor

LONG ACTING

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

19 20 21 22 23 24

x B L D x

Long-Acting InsulinBasaglar (biosimilar Lantus)

Onset: 1-2 hrsPeak: peaklessDuration: 24 hrs

Basaglar Generic Name-glargine Brand Name: Basaglar Manufacturer: Eli Lilly Form: analog Delivery: 3 ml pen fill Storage-pen in use 28 days Onset: one hour Peak: no peak Duration: 24 hours

Ultra Long Acting InsulinGlargine U-300/Toujeo

Onset: 6 hrsPeak: peaklessDuration: 36 hrs

Toujeo Generic Name: glargine U-300 Brand Name: Toujeo Manufacturer: Sanofi Form: Analog Delivery: (450unit) prefilled pen Storage-pen in use good for 42 days Onset: 6 hours Peak: No peak Duration: 36 hours Maximum single injection: 80 units

Comparison of U-100 & U-300 insulin glargine

U-100 U-300

Ultra Long Acting InsulinDegludec/Tresiba

Onset: ½-1.5 hrsPeak: peaklessDuration: 42 hrs

Tresiba Generic Name: degludec Brand Name: Tresiba Manufacturer: Novo Nordisk Form: Analog Delivery: prefilled pen u-100 (300) u-200 (600) Storage: in use room temperature up to 48 days Onset: one hour Peak: No peak Duration: 42 hours Maximum single dose: 160 units

WHAT’S THE LATEST?

Insulin + GLP-1 Soliqua 100/33 (glargine 100/lixisenatide

33mcg per ml) Using <60units of basal or lixisenatide If <30 units/day --start with 15 units

(15glargine/5mcg lixisenatide); 30-60 units/day—start 30 units Max dose 60 units (60G/20 lixisenatide) One hour prior to 1st meal Supplied in 3ml prefilled pens

Insulin + GLP-1 Xultophy 100/3.6 (100 units degludec/3.6

mg liraglutide Using less than 50 units basal or liraglutide < 1.8 Starting dose 16 units (16 units degludec/0.58mg Max dose 50 units (50 units degludec/1.8mg

liraglutide Independent of food Supplied in 3ml prefilled pens

Fiasp Generic Name- fast acting insulin aspart Brand Name- Fiasp Manufacturer- Novonordisk Form- analog Delivery- 3ml pre-filled pen, 10 mL vials Storage-open in use 28 days-room temperature Onset- 2.5 minutes (dose dependent) Peak- 63 minutes (dose dependent) Duration- 5-7 hours (dose dependent)

STARTING INSULIN & ADJUSTING INSULIN

Who Should be on Insulin?

Type 1 diabetes at any age Uncontrolled hyperglycemia on oral agents Presentation with decompensated diabetes Pregnant women with hyperglycemia Critical illness – e.g. myocardial infarction, sepsis No oral access Oral agents contraindicated

e.g. NPO, renal or hepatic disease

How much insulin to start?New start: Usual starting total daily dose: 0.3-0.6 units/ kg

larger dose if: steroid therapy, massive obesity smaller dose if: renal failure, hepatic failure,

malnourished, type 1 diabetes

Half basal, half prandial/bolus ± correctional

The Case of AB (cont) 37 yo male. 222#, BMI- 33, BP 150/90, A1c

8.8%

It’s time for insulin– What to do?

The Case of AB (year 10) He is now 44 years old. He has regained

the weight he previously lost plus an additional 20#--254# (BMI 38). He is not checking BG often, but no feelings of lows. His A1c is 10%.

He states he is taking insulin as prescribed, but BG remains elevated What to do now?

If noninsulin monotherapy at maximal tolerated dose does not achieve or maintain the A1C target over 3 months, add a second oral agent, a GLP-1 receptor agonist, or insulin.

Use a patient-centered approach to treatment. Don’t delay insulin initiation in patients not

achieving glycemic goals.

Pharmacological Therapy For T2DM

American Diabetes Association Standards of Medical Care in Diabetes. Approaches to glycemic treatment. Diabetes Care 2016; 39 (Suppl. 1): S52-S59

ADA, Diabetes Care,2016;

Glycemic goals for some older adults might be relaxed but hyperglycemia leading to symptoms or risk of acute hyperglycemic complications should be avoided in all patients.

Hypoglycemia should be avoided in older adults with diabetes. It should be screened for and managed by adjusting glycemic targets and pharmacologic interventions.

Recommendations: Older Adults

American Diabetes Association Standards of Medical Care in Diabetes. Older adults. Diabetes Care 2016; 39 (Suppl. 1): S81-S85

Questions?