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Diabetes Update

Division of Endocrinology

Department of Medicine

Wayne State University Medical School

Detroit, Michigan

Part 2 of 3

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Why the Interest in Incretins ?

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The Incretin Defect in Type 2 Diabetes

Insulin Resistance

Incretin“Defect”

Relative Insulin Deficiency

HyperglycemiaType 2 Diabetes

Incretin effect accounts for up to 70% of the insulin response to oral glucose intake1

1. Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004;287(2):E199-E206.

GLP-1 secreted upon the ingestion of food

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Lifestyle + MET + PIO + SFU

Lifestyle + MET + PIO + SFU

“If hypoglycemia is particularly

undesirable…” and/or “promotion of

weight loss is a consideration…”

“If hypoglycemia is particularly

undesirable…” and/or “promotion of

weight loss is a consideration…”

ADA/EASD Consensus Statement Includes a GLP-1 Receptor Agonist

STEP 1 At diagnosis: Lifestyle + MET

STEP 2 Tier 1: Well-validated core therapies*

STEP 3 Lifestyle + MET + intensive insulin

OR

If A1C ≥7%If A1C ≥7%

MET, metformin PIO, pioglitazone SFU, sulfonylurea

*Validation based on clinical trials and clinical judgment.†Insufficient clinical use to be confident regarding safety. Adapted from Nathan DM, et al. Diabetes Care. 2009.

Lifestyle + MET + basal insulin

Lifestyle + MET + basal insulin

Lifestyle + MET + SFU

Lifestyle + MET + SFU

Lifestyle + MET + basal insulin

Lifestyle + MET + basal insulin

Tier 2: Less well-validated therapies*

Lifestyle + MET + PIO

Lifestyle + MET + PIO

Lifestyle + MET +GLP-1 receptor

agonist†

Lifestyle + MET +GLP-1 receptor

agonist†

EXUBERAEXUBERA®®

(insulin human [rDNA origin])(insulin human [rDNA origin])Inhalation PowderInhalation Powder

Liraglutide (Victoza)Liraglutide (Victoza)and Exenatide (Byetta)and Exenatide (Byetta)

Newer GLP 1 analogue.Newer GLP 1 analogue.

Indicated in monotherapy or in combination with Indicated in monotherapy or in combination with metformin, SU, TZD, or combination therapy.metformin, SU, TZD, or combination therapy.

Dosed once or twice daily Dosed once or twice daily

Uses the convenient pen.Uses the convenient pen.

Maintains weight loss and glycemic control.Maintains weight loss and glycemic control.

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Why Insulin in Type 2 DiabetesWhy Insulin in Type 2 Diabetes??

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Mimicking Physiology: Mimicking Physiology: Basal and Prandial InsulinBasal and Prandial Insulin

Breakfast Lunch Dinner

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Pla

sma

Insu

lin

Time

Basal1/day

Prandial Insulin 3/day

Plus