New Insulin Formulations Guillermo Umpierrez, MD, FACP, FACE Professor of Medicine Emory University...

10
New Insulin Formulations Guillermo Umpierrez, MD, FACP, FACE Professor of Medicine Emory University School of Medicine Part 1

Transcript of New Insulin Formulations Guillermo Umpierrez, MD, FACP, FACE Professor of Medicine Emory University...

New Insulin Formulations

Guillermo Umpierrez, MD, FACP, FACEProfessor of Medicine

Emory University School of MedicinePart 1

BANTING-1891-1941 & BEST-1899-1978

First commercial insulin

Milestones in Insulin Development

Tattersall RB. In: Pickup JC, Williams G, eds. Textbook of Diabetes. 3rd ed. Blackwell Science: Malden, MA; 2003:1.1-1.22; Drugs@ FDA;

http://diabetes.webmd.com/news/20071018/pfizer-quits-inhaled-insulin-exubera.

1920 1930 1940 1960 1970 1980 2000 201019901950

Insulin discovered (1921)

First human treatment with bovine insulin (1922)

Protamine and protamine zinc insulins developed (1936)

NPH insulin developed (1946)

Lente (zinc) insulins developed (1952)

Synthetic human insulin developed (1965)

Recombinant human insulin developed (1979)

Insulin pump developed (1978?)

Insulin pen developed (1981)

Insulin lispro approved in US (1996)

Insulin aspart and insulin glargine approved in US (2000)

Insulin glulisine (2004)

Insulin detemir approved in US(2005)

Inhaled insulin (2006) 2014

2013

Degludec (2013)

In development:Degludec U-200Glargine U-300Pegylated LisproBiosimilars

2014

Currently Available Basal Insulins

Lucidi D, et al. Diabetes Care. 2011;34:1312-1314. Niswender K, et al. Clin Diabetes. 2009;27:60-68.

Insulin Glargine vs NPH Insulin Added to Oral Therapy: FPG and

HbA1c

Riddle M, et al. Diabetes Care 2003;26:3080−6.

0 4 8 12 16 20 246

7

8

9

Hb

A1c

(%

)

Insulin glargineNPH

756 patients previously treated with 1―2 OHAs and HbA1c >7.5%

Mean daily insulin dose Insulin glargine: 47 units

NPH: 42 units

Time (weeks)

10

7

50 4 8 12 16 20 24

FP

G (

mm

ol/l

)

Time (weeks)

6

8

9

Treat to Target Trial: Frequency of

Hypoglycemia

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

900

Glargine

NPH

24 120

800

Time (days)

700

600

500

400

300

200

100

00 48 72 96 144

Cu

mu

lati

ve n

um

ber

of

even

tsD

ocu

men

ted

PG

< 5

6 m

g/d

L (

3.1

mm

ol/

L)

Glargine

NPH

168

41% RRRP <0.003

Giugliano et al. Diabetes Research & Clinical

Practice 92 (2011) 1–10

29 trials, with 17,588 patients

HbA1c < 7% was achieved in 41.4% (95% CI, 35.6–47.4%). First insulin treatment, lower insulin and use of 2 oral drugs were predictors of response.

Hypoglycemia ranged from 0 to 4.71 events/patient/30 days

Weight gain ~1.75 kg

HbA1c < 7% was achieved in 41.4% (95% CI, 35.6–47.4%)

Product Onset, h Peak, hEffective Duration,

h

Human biphasic insulin

70% NPH/30% regular 0.5-1 Dual 10-16

Analogue biphasic insulin

75% NPL/25% lispro < 0.25 Dual 10-16

50% NPL/50% lispro < 0.25 Dual 10-16

70% aspart protamine/30% aspart < 0.25 Dual 15-18

American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. 2011:1-68.

Available Premixed/Biphasic Insulins

NPH, neutral protamine Hagedorn; NPL, neutral protamine lispro suspension.