from metform and beyond: the latest in diabetes therapies
TRANSCRIPT
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