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Injectables in Diabetes

Fadi Al-Khayer, MD, FACE

Connecticut Endocrinology Center

Storrs Mansfield, CT

In the United States, approximately 30 million persons have

diabetes or approximately 7 % of the US people.

Nearly 1.9 million Americans develop diabetes every year, or

approximately 5205 every day.

Individuals with type 2 diabetes may have the disease and

remain undiagnosed for over 10 years.

Worldwide, the number of people with diabetes is expected to

rise to more than 400 million by year 2025.

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The American Diabetes Association (ADA) Standards for

Glycemic Control in Diabetes Mellitus

Parameter Normal Goal Additional action

suggested

Fasting or preprandial

glucose (capillary

whole blood)

< 100 80-120 <80 or >140 mg/dL

Bedtime glucose

(capillary whole

blood)

<120 100-140 <100 or >160 mg/dL

Hemoglobin A1c (%) <6% <7% >8%

The American College of Endocrinology Targets for

Glycemic Control

Target

Fasting glucose (capillary

whole blood)

< 110 mg/dL

Postprandial glucose

(capillary whole blood)

< 140 mg/dL

Hemoglobin A1c < 6.5 %

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Exercise is crucial!

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How good is the control of

diabetes?

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A1C Is a Combination of Both Fasting and Mealtime Glucose Measurements

Monnier L, et al. Diabetes Care. 2003;26:881-885.

•At A1C ranges of 7.3% to 9.2%,

overall glycemia is impacted

similarly by fasting blood

glucose (FBG) and

postprandial glucose (PPG)

•As A1C approaches goal,

elevated PPG contributes more

to the elevation in A1C

Diabetes is not that easy to

treat!

Relationship of A1C to Risk of

Microvascular Complications

Adapted with permission from Skyler JS. Endocrinol Metab Clin North Am. 1996;25:243

Retinopathy

Nephropathy

Neuropathy

Microalbuminuria

Rela

tiv

e R

isk

A1C (%)

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13

11

9

7

5

3

1

6 7 8 9 10 11 12

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The Pathogenesis of Type 2 Diabetes

An Imbalance of Beta-Cell Workload and Beta-Cell Response

Decreased Beta-Cell Response

Insulin resistance

Obesity

Food intake

Gastric Emptying – Rate of nutrient absorption

Glucagon secretion

Hepatic glucose output

Insulin secretion in

response to elevated

glucose

First-phase

insulin response

Increased

Beta-Cell

Workload

Hyperglycemia

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Barriers to Injectables, patients

Injection Technique

Inconvenience

Embarrassment

Frequency of injections

Type of injections

Injection Anxiety

FEAR OF PAIN

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Barriers to Injectables,

Physicians

Patients education time

Concern with angering or losing patients

Concern with patient's compliance

FEAR OF PAIN

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Fear of Pain

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Fear of Pain

Was quite overestimated by physicians

rather than patients!

In one study, only 12% of patients were

afraid of injectables

Vs 48% of physicians who had this fear!

Remember, insulin is one of the most

UNPOPULAR medicines among

physicians! 21

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Injections are quite easy!

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Patients may surprise you!

In a survey of 797 patients with diabetes

80% of insulin naive patients were open to

taking insulin

20% opposed the idea

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Injectable medicines in

diabetes

Insulins (Basal, rapid, mixed)

GLP 1 Analogues (Byetta, Victoza,

Bydureon)

Amylin Analogues (Symlin)

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Different Insulin Preparations Currently Available in the United States

Insulin Type Onset (hr) Duration (hr) Peak (hr)

Short acting (regular insulin, R) 0.5-1.0 6-8 2-4

Rapid acting analogues

Lispro (Humalog®)

Aspart (NovoLog®)

Glulisine (Apidra®)

0.05-0.15

0.05-0.15

0.05-0.15

3-5

3-5

3-5

1-2

1-2

1-2

Intermediate acting

NPH

Lente

1-3

1-3

13-18

13-20

5-7

4-8

Long acting

Ultralente

Glargine (Lantus®)

Detemir (Levemir®)

2-4

1.5

1.5

18-30

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Up to 24

10-14

None

None

Combinations

70/30 NovoLog® mix, 70% NPA, 30%

aspart)

75/25 Humalog® mix, 75% NPL, 25%

lispro

50/50 Humalog® mix, 50% NPL, 50%

lispro

and others

0.5-1.0

0.05-0.15

0.5-1.0

0.05-0.15

0.05-0.15

13-18

13-18

13-18

13-18

13-18

Dual

Dual

Dual

Dual

Dual

Insu

lin

Eff

ect

B D L HS

Bolus insulin

Basal insulin

Mimicking Nature The Basal-Bolus Insulin Concept

Endogenous insulin

Adapted with permission from McCall A. In: Insulin Therapy. Leahy J, Cefalu W, eds. New York, NY: Marcel

Dekker, Inc; 2002:193

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Basal Insulins

Lantus and Levemir (and degludec insulin

within one year from today)

Easy to initiate

10 units once a day

Monitor fasting glucose and increase (or

decrease) the dose by one unit every day

till the fasting glucose is between 80-120

mg/dL

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Ultra rapid acting insulin

analogues

Humalog, Novolog, and Apidra

Easiest way to initiate is WITH the largest

meal of the day

Start 4 units with the largest meal

Monitor the PPG (two hours after the

meal), and increase (or decrease) the dose

by 1 unit every day till the PPG is below

140-150 mg/dL.

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GLP1 Analogues

Byetta is twice a day (5 mcg bid then in one month

increase to 10 mcg bid)

Victoza is once a day (start 0.6 mg once a day for 1

week then increase to 1.2 mg a day then if tolerated

you can increase it to 1.8 mg a day)

Bydureon is once a week (2 mg a week, needs to be

mixed)

Interesting combination with insulin 29

Amylin, the Missing Hormone

•Neuroendocrine hormone that is deficient in

diabetes

•Colocated and cosecreted with insulin from

pancreatic beta cells

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Unger RH, Foster DW. In: Wilson JD, Foster DW, eds. Williams Textbook of Endocrinology.

8th ed. Philadelphia, PA: WB Saunders; 1992:1273-1275.

Amylin IHC staining

Insulin Immunofluorescence

Beta cell islet section

Human amylin

SYMLIN® Works in 3 Ways to Improve

Postprandial Glucose Control

•Enhances feeling of fullness at meals

•Slows inappropriately accelerated

gastric emptying

•Decreases hepatic glucose output

via suppression of postprandial

pancreatic glucagon secretion

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Please see the Important Safety Information on slides 7, 27, and 28 and

accompanying SYMLIN Prescribing Information, including the Boxed Warning

regarding insulin-induced severe hypoglycemia.

SYMLIN (pramlintide acetate) Injection:

Fine Tuning Blood Glucose Control

With an Added Benefit of Weight Loss

©2009 Amylin Pharmaceuticals, Inc.

All rights reserved. 01-08-6614-C The SYMLIN mark, SYMLIN design mark, SymlinPen mark, and SymlinPen design mark are

registered trademarks of Amylin Pharmaceuticals, Inc. SYMLIN Support Program is a service mark of Amylin

Pharmaceuticals, Inc. All other brand names are the properties of their respective owners.

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Pearls

Type 2 diabetes is a progressive and complex

disease, requires multifactorial approach to

treatment

The ADA, EASD, AACE, and ACE consensus

algorithms for type 2 diabetes include multiple

injectable treatment options

Barriers to the use of injectable therapy exist among

patients and health care professionals

it is important not to compromise patient care

because of concerns regarding use of injectable

therapy

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Practical Points

Many pharmaceutical companies have educators

that are ready to teach your staff how to initiate their

medicines

The pens are quite easy and teach and use

Utilize the education materials and 24 hour support

provided by the manufactures for patients. English

and Spanish services are typically provided

Risk of hypoglycemia, while exists with injectable

medicines, is still low

Always reduce the dose of SU by 50% when adding

an injectable medicine 36