Insulin initiation and intensification in the type 2 diabetic patient
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Insulin Initiation and Intensification in the Type 2 Diabetic Patient. Jorge De Jesus MD FACE . Disclosures.

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Insulin Initiation and Intensification in the Type 2 Diabetic Patient

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Insulin initiation and intensification in the type 2 diabetic patient

Insulin Initiation and Intensification in the Type 2 Diabetic Patient

Jorge De Jesus MD FACE


Disclosures

Disclosures

  • Dr Jorge De Jesús has received honorariums as speaker for the following pharmaceutical companies: Bristol Myers-Squibb; Merck; Eli-Lilly; Astra-Zeneca; Boehringer- Ingelheim; Janssen

  • Dr Jorge De Jesús has no conflicts of interests with any entity for the information included in this presentation

Jorge De Jesús MD FACE


What is cell dysfunction

What is -cell dysfunction?

Major defect in individuals with type 2 diabetes

Reduced ability of -cells to secrete insulin in response to hyperglycemia

DeFronzo RA, et al. Diabetes Care 1992; 15:318–354.


Insulin initiation and intensification in the type 2 diabetic patient

Why insulin therapy in type 2 diabetes?


Antihyperglycemic monotherapy maximum therapeutic effect on a1c dependent upon starting a1c

Antihyperglycemic Monotherapy Maximum Therapeutic Effect on A1C, dependent upon starting A1C

Baseline A1C

8.51

Acarbose

Nateglinide

8.3-8.52

Sitagliptin

Bromocriptine

7.73

7.8-12.54

Liraglutide

8.2-8.55

8.06

Exenatide

10.0-10.37

Pioglitazone

8.8-9.08

Repaglinide

Glimepiride

7.79

Glipizide GITS

8.3-8.810

9.7-10.111

Metformin

Insulin

0

-1.0

-1.5

-2.0

-0.5

Reduction in A1C Level (%)

1. Precose [PI]. West Haven, CT: Bayer; 2003; 2. Hanefeld M et al. Diabetes Care. 2000;23:202–207; 3. Sitagliptin PI, Merck & Co, Inc, Whitehouse Station, NJ, 2010;1-23; 4. Kerr et al. Ann Pharm. 2010;44:1777-1785; 5. Blonde et al. DiabObesMetab. 2009;11(S3):26-34; 6. Nelson P, et al. Diabetes TechnolTher. 2007;9:317–326; 7. Aronoff S, et al. Diabetes Care. 2000;23:1605–1611; 8. Lebovitz HE, et al. J ClinEndocrinolMetab. 2001;86:280–288; 9. Goldberg RB et al. Diabetes Care. 1996;19(8):849-856; 10. Simonson DC et al. Diabetes Care. 1997;20(4):597-606; 11. Garber AJ, et al. Am J Med. 1997;102:491–497.


Insulin initiation and intensification in the type 2 diabetic patient

Insulin

  • Remains the most powerful tool we have to control blood glucose

  • Dosing potential and A1C reduction only limited by risk of hypoglycemia

    • Patients with type 2 diabetes are at lower risk for hypoglycemia than type 1 patients

Nathan DM, et al. Diabetes Care. 2006;29:1963-1972.


Insulin initiation and intensification in the type 2 diabetic patient

When To Start Insulin in T2DM

  • When combination oral/injectable agents become inadequate

  • Have poor AM or daytime glycemic control

  • Unacceptable side effects of oral/injectable agents

  • Patient wants more flexibility

  • Special circumstances (i.e. steroids, infection, pregnancy)

  • Patients with hepatic or renal disease


Normal insulin secretion

Normal Insulin Secretion

75

Bolus or Meal Response

Dawn Phenomenon

Basal or Background

50

Plasma Insulin (U/mL)

Decrease at Night

25

0

4:00

8:00

12:00

16:00

20:00

24:00

4:00

8:00

Time (hrs)

Polonsky W. Diabetes Educ. 2007;33(suppl 3):241S–244S.


Treat to target study insulin glargine vs nph insulin added to oral therapy

Treat to Target StudyInsulin Glargine vs. NPH Insulin Added to Oral Therapy

  • 9

Insulin glargine

NPH insulin

  • 8

Mean A1C(%)

  • 7

Target A1C (%)

60% reach target A1C < 7%

  • 6

  • 0

  • 4

  • 8

  • 12

  • 16

  • 20

  • 24

Weeks

Riddle MC, et al. Diabetes. 2002;51(suppl 2):A113.


Treat to target study cumulative incidence of hypoglycemia n 756 pg 72 mg dl 4 0 mmol l

Treat to Target Study: Cumulative Incidence of Hypoglycemia (N=756) PG 72 mg/dL ( 4.0 mmol/L)

NPH insulin

Insulin glargine

Insulin Glargine vs. NPH in Overweight Patients with T2DM

Cumulative Hypoglycemic Events

NPH, Neutral protamineHagedorn; PG, plasma glucose.

Riddle MC, et al. Diabetes Care. 2003;26:3080-3086.


Insulin initiation and intensification in the type 2 diabetic patient

Detemir + OAD

NPH + OAD

Risk of Hypoglycemia with Detemir

p < 0.001

18

16

14

12

Hypoglycemic events per patient per year

10

8

p < 0.001

6

4

2

0

Overall

Nocturnal*

* Any episode between 11 pm and 6 am

Please see full prescribing information.

Insulin detemir [package insert]. Bagsvaerd, Denmark; Novo Nordisk; 2009. NPH insulin [package insert]. Bagsvaerd, Denmark; Novo Nordisk; 2009. Hermansen K et al. Diabetes Care. 2006;29:1269-1274.


Insulin detemir vs nph weight profile

Insulin Detemir vs. NPH Weight Profile

3

Insulin detemir

*p<0.05, insulin detemir vs NPH insulin

NPH insulin

2.5

2

*

*

*

*

*

*

*

*

*

*

*

*

1.5

1

Weight change (kg)

0.5

0

Studies in type 2 diabetes

-0.5

-1

Hermansen

Standl

Vague

De Leeuw

Pieber

Pieber

Home

Home

Russell-Jones

Hermansen

Rašlová

Haak


Insulin initiation and intensification in the type 2 diabetic patient

  • Long-acting insulin analogs are superior to NPH insulin because they provide a fairly flat response for approximately 24 hours and pro-vide better reproducibility and consistency both between subjects and within subjects, with a corresponding reduction in the risk of hypoglycemia.

  • Rapid-acting insulin analogs are superior to Regular because they are more predictable.


24 hour insulin secretion and replacement

24-Hour Insulin Secretion and Replacement

Aspart

Lispro

Glulisine

Regular

50

Insulin

(µU/mL)

25

Total Daily Dose (TDD)

~50% Bolus Insulin

~50% Basal Insulin

0

Breakfast Lunch Dinner

Detemir Glargine

NPH

Riddle MC et al. The American Journal of Medicine. 2005;118(5A):14S–20S. Tanaka M. et al. The Journal of International Medical Research. 2010;38:674–68.


Example starting multiple daily injections in 100 kg person with moderate insulin resistance

Example: Starting Multiple Daily Injections in 100-kg Person with Moderate Insulin Resistance

  • Starting dose = 0.5 x wt in kg

    • 0.5 x 100 kg = 50 units

  • Basal dose = 50% of starting dose at bedtime

    • 50% of 50 units = 25 units at bedtime

  • Total bolus dose = 50% of starting dose evenly distributed1/3 at each meal

    • 25 units ÷ by 3 meals = 8 units before meals (TID)


Meal insulin rapid acting analogs lispro aspart glulisine vs regular

Meal Insulin Rapid-Acting Analogs (Lispro, Aspart, Glulisine) vs Regular

Timing of

food absorbed

Analog insulin

10

8

6

Insulin

Activity

4

Regular Human Insulin

2

0

1

2

3

4

5

6

7

8

9

10

11

12

0

Hours

Howey DC, et al. Diabetes. 1994;43:396–402.


Barriers to insulin initiation

Barriers to insulin initiation

Patients refusal

Insulin costs

Fear of Hypoglycemia

Myths

Medical Inertia

Patient education is time consuming

Sometimes we transmit our concerns to patients even with non-verbal communication


Insulin initiation and intensification in the type 2 diabetic patient

Es mejorprenderunavelitaquemaldecir la oscuridad

Gracias

Agradecer al Dr Harry Jimemnez por la ayuda en algunos visuales de esta presentacion


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