From Metformin and Beyond: The Latest in Diabetes Therapies

Mansur E. Shomali, MD, CMAssociate Director, Diabetes & Endocrine Center, Union Memorial Hospital

Program Director, Union Memorial Hospital Training Program in Endocrinology, Diabetes & Metabolism

Clinical Assistant Professor of Medicine, University of Maryland School of Medicine

1500 b.c. Ebers papyrus

1922 Banting & Best

1993 DCCT published

2001 Leuven study

10,000 1,000 100 10 1

number of years ago (log scale)

Diabetes increases risk of M.I. or stroke by 4 X

22 million patients with Diabetes

300,000 die each year

Diabetes decreases life expectancy by about 10 years

What is the clinical evidence that treating diabetes can improve health and prolong life?

"It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity…”

-Dickens, C.

…for clinical trials in diabetes…”

-Shomali, M.

Hyperglycemia is bad for you.

Hypoglycemia is bad for you.

UKPDS Group. Lancet. 1998;352:837-853.

Effect of Glycemic Control in UKPDS

Any diabetes related*

MI

Stroke

PVD

Microvascular

40.9

14.7

5.6

1.1

8.6

46

17.4

5

1.6

11.4

0.029

0.052

0.52

0.15

0.0099

11

16

–

–

25

(rate/1000 pt yrs)

*Combined microvascular and macrovascular events

Intensive

%Decrease

(rate/1000 pt yrs) P

Conventional

Endpoints

The Steno Diabetes Study

reduce dietary fat

regular exercise

smoking cessation

A1C <6.5%

BP <130/80

t. chol <175

trig <150

aspirin

dietary supplement (vit E, vit C, folate, chromium)

ACE-I regardless of BP

Gaude P et al. N Engl J Med 348:383–393, 2003

The Steno Diabetes Study

PROactive Study

Dormandy JA et al. Lancet 366 Oct 2005

PROactive Study

Dormandy JA et al. Lancet 366 Oct 2005

pioglitazone placebo

A1C -0.8 -0.3

Trig -11.4 -1.8

HDL +19 +10

sBP -3 mmHg 0 mmHg

Nissen S and Wolski K. N Engl J Med 2007;356:2457-2471

Myocardial Infarctions and Cardiovascular Deaths in Rosiglitazone Trials

Nissen S and Wolski K. N Engl J Med 2007;356:2457-2471

Myocardial Infarctions and Cardiovascular Deaths in Rosiglitazone Trials

ACCORD (Action to Control Cardiovascular Risk in Diabetes)

10,000 patients

5,000 < 6%

5,000 7-7.9%

Deaths per 1000 patients per year

14

11

A1C

ENHANCE Trial

ezetimibe/simvastatin (Vitorin) vs

simvastatin alone

carotid intima-media thickness

Fehse F et al. Diabetes 2004

Exenetide and beta cell responses

Kolterman OG et al J Clin Endocrinol Metab 2003

Exenetide and beta cell responses