...

371

4 5

50%

60

50%

4.8 . 471
$
2012

Tsunami of Diabetes Anticipated to Hit the United

States
John Anderson, MD, warned of an epidemic "this
tsunami of diabetes" that will hit the United States,
and questioned whether doctors and researchers are
ready to meet the challenge. The incidence of diabetes is
expected to increase from 14%

to 23% by 2025.
439 million people

By 2030, an estimated
worldwide will be affected by diabetes, and the cost of
caring for these people is rising at a rate of about 8% per
year, totaling around $245

billion in 2012.

 2
&
Met
TZD
GLP-1
GLP-1

SGLT-2 I

GLP-1

SU
Glinides
GLP-1

Met
GLP-1
DPP-4 I

TZD

Met
TZD
GLP-1

UKPDS

DCCT / EDIC*

ACCORD

ADVANCE

VADT

UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854, Holman RR et al. N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med
1993;329;977. Nathan DM et al. N Engl J Med. 2005;353:2643. Gerstein HC et al. N Engl J Med. 2008;358:2545. Patel A et al. N Engl J Med 2008;358:2560.
Duckworth W et al. N Engl J Med 2009;360:129. (erratum: Moritz T. N Engl J Med 2009;361:1024)

(ALL-CAUSE)


67 28,5 Kg/m2 &
10
.
2.


.

117 mg/dl
OGTT.
OGTT: 0: 108 mg/dl
120: 210 mg/dl

HbA1c: 7,0%
eGFR: 85 mL/min

:
.
.
. 1
. 2
. LADA

:
. HbA1c < 7.0%
. HbA1c < 6.5%
. HbA1c < 5.9%
. GLP-1 analogs HbA1c < 6.5%
. SU HbA1c < 6.5%

3 (-.-)
:


, ,
(TC, HDL, LDL, TG,
FFA)




(UKPDS)


Association between first-line monotherapy
with sulfonylurea versus metformin and risk
of all-cause mortality.
Jenkins, Jones et al. EASD meeting 2013

Evaluation of risk of all-cause mortality for 92.498 patients

exposed to first-line diabetes monotherapy with either
sulfonylureas or metformin (2000-2012).
76,811 pts on metformin & 15,687 pts on sulfonylureas.
Mortality was significantly increased in patients prescribed
sulfonylureas as first-line, glucose lowering monotherapy,
compared with metformin monotherapy. Whilst residual
confounding and confounding by indication may remain, this
study indicates that treatment with first-line monotherapy with
sulfonylureas should be reconsidered.

69 27,5 Kg/m2 &

(
) &
2 3 2/.
2
78 .
3-4
.
SMBG :
FPG: 110-143 mg/dl
PPG: 160-240 mg/dl
HbA1c: 7.4%, eGFR: 74 mL/min

To
:
.

.
. TZD
. SU
. 1

(TC, HDL,
LDL, TG)

R. Moses, S. Kalra et al. A Randomized Controlled Trial of the Efficacy and Safety of Saxagliptin as Addon Therapy in
Patients With Type 2 Diabetes and Inadequate Glycemic Control on Metformin Plus a Sulfonylurea, Diabetes, Obesity &
Metabolism, 13 November 2013

FPG

HbA1c

PPG

% HbA1c<7.0%


DPP4-I &

Primary

TECOS (Sitagliptin vs. placebo)
CAROLINA (Linagliptin vs. placebo)
CARMELINA (Linagliptin vs. placebo)


57 35,8 Kg/m2
A :
OEM 6
2.
ACE-I, -Blocker, ASA, Statin &
Metformin 850 mg X 3.
2

lifestyle modification.
17

.
,
.
:
HbA1c: 8.9%, eGFR: 65 mL/min
SMBG:
FPG 180 mg/dl & PPG 260 mg/dl

O HbA1c 8.9%
7.0% ( 1.9%). To
:
. Met + SU
. Met + Insulin
. Met + GLP-1 + Pio
. Met + DPP4-I
. Insulin (Basal/Bolus)


Pioglitazone

Placebo

post-PROactive (6 PROactive + postPROactive (3 years)

years)
PROactive (9 years)
50%
40%

30%
20%
*

10%
0%

n=2.605

n=2.633

n=1.820

n=1.779

n=2.605

n=2.633

The improved cardiovascular outcome seen with pioglitazone during the double-blind
period of PROactive did not persist during the observational period in the absence of
continued pioglitazone treatment.
*p<0.05 vs placebo

(TC, HDL, LDL, TG)
,


(animal models)
EF 72h GLP-1

PCI

Triple Therapy for New-Onset Diabetes:

A Paradigm Shift
Newly diagnosed type 2 diabetes patients started on

therapeutic agents simultaneously (metformin,

pioglitazone, and exenatide) had greater and more
durable reductions in HbA1c, less hypoglycemia, and
less weight gain than those treated with conventional
therapy, according to a clinical trial by Muhammad
Abdul-Ghani, MD, from the University of Texas Health
Science Center at San Antonio that generated
excitement.


Initial triple combination therapy is more effective
and safer than stepwise add on conventional
therapy in newly diagnosed type 2 DM
Background and aims
To compare the efficacy and safety of initiating therapy in new onset
T2DM with triple therapy (metformin/pioglitazone/exenatide) versus
metformin followed by sequential addition of sulfonylurea and basal
insulin.
Materials and methods
144 newly diagnosed T2DM (age = 451 y; BMI=360.5; HbA1c =
8.60.1%; diabetes duration = 5.60.5 mo) were randomized to receive
metformin (10002000 mg/d) plus pioglitazone (1545 mg/d) plus
exenatide (510 g BID) (Triple Therapy, n=71) or escalating dose of
metformin (10002000 mg/d) followed by sequential addition of
sulfonylurea (glipizide, 20 mg/d) and basal insulin to maintain HbA1c <
6.5 (Conventional Therapy, n = 73).
R.A. DeFronzo, C. Puckett, J. Adams, E. Cersosimo, C. Triplitt, M. Abdul-Ghani;
Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.


Results
In subjects receiving Triple Therapy, HbA1c decreased
from 8.6 to 6.1% at 6 mo and to 5.9% at month 24. In
the Conventional Therapy arm, HbA1c declined to
6.3% at 6 mo and subsequently increased to 6.6% at
mont 24. More subjects in the conventional arm failed
to achieve the treatment HbA1c goal <6.5% (35 vs
16%, respectively, p<0.0001). Moreover, as the Box
plot below demonstrates, >90% of subjects receiving
the triple therapy maintained HbA1c <7.0% at 2 years
compared to <75% of subjects in the conventional
therapy arm. Despite significantly lower HbA1c,
subjects in Triple Therapy arm experienced a 13.6fold lower rate of hypoglycemia compared to
subjects receiving Conventional Therapy. Lastly,
subjects in the Triple Therapy arm experienced mean
weight loss of 1.2 kg compared to mean weight gain
of 3.6 kg (p=0.02) in subjects in the Conventional
Therapy arm.


Initial triple combination therapy is more effective and safer than
stepwise add on conventional therapy in newly diagnosed type 2
diabetes mellitus

Conclusion
The present results demonstrate that antidiabetic therapy targeting the
core metabolic pathophysiologic disturbances (insulin resistance and
beta cell dysfunction) responsible for hyperglycemia is more effective
and safer than therapy simply aimed at lowering the plasma glucose
concentration without correcting the underlying metabolic abnormalities
present in T2DM.

R.A. DeFronzo, C. Puckett, J. Adams, E. Cersosimo, C. Triplitt, M. Abdul-Ghani;

Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

EXSCEL (Exenetide once weekly vs. placebo)

FREEDOM-CVO (Exenatide vs. placebo)
LEADER (Liraglutide vs. placebo)
ELIXA (Lixisenatide vs. placebo)

(
)
- (?)
IGF (?)

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