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Journal Reading

Penyaji :
Scholastyka Febrylla
Pembimbing :
dr. I Ketut Sujana, Sp.PD

Kepaniteraan Klinik Ilmu Penyakit Dalam


Rumah Sakit Universitas Tanjungpura
Fakultas Kedokteran Universitas Tanjungpura
2016

long-term
cardiovascu
lar
safety???
antihyperglyce
mic agents

Backgrou
Sitagliptin: dipeptidyl nd

peptidase 4 (DPP-4)
inhibitor
suppressing glucagon
DPP-4 inhibitors:
levels
no increase or
decrease in the
increasing
suppressing glucagon
levels and
increasing
endogenous insulin number of major
Good
glycemicendogenous insulin
adverse
secretion
secretion
control among
cardiovascular
patients
events
with type 2
possible risk of
diabetes
hospitalization for

heart failure (24 to


25%)

diabetes-related
microvascular
complications

SAFE?
??

Method
randomized, double-blind, placebo-controlled,
event-driven trial
673
sites 38 countries
suppressing
glucagon
levels and increasing endogenous insulin
secretion Study population:
type 2 diabetes
established cardiovascular disease (CAD, ICD, or
atherosclerotic PAD)
at least 50 years of age
glycated hemoglobin level of 6.5 to 8.0%
treated with stable doses of one or two oral
antihyperglycemic agents (metformin, pioglitazone, or
sulfonylurea) or insulin (with or without metformin)

Method
Excluded if:
had taken a DPP-4 inhibitor, glucagon-like peptide-1
receptor agonist, or thiazolidinedione (other than
pioglitazone) during the preceding 3 months;
had a history of two or more episodes of severe
(defined as requiring third party assistance)
suppressing hypoglycemia
glucagon
during the
preceding 12
months;
levels and increasing
endogenous
insulin
secretion estimated glomerular filtration rate (eGFR) was less than
30 ml per minute per 1.73 m2

14,671 patients, added either sitagliptin or


placebo to the existing therapy (1:1 ratio)
Median follow up: 3 years

Method
Primary composite cardiovascular outcome:
the first confirmed event of cardiovascular death,
nonfatal myocardial infarction, nonfatal stroke, or
hospitalization for unstable angina.
suppressing
glucagon composite cardiovascular outcome:
Secondary
levels and increasing endogenous insulin
the first confirmed event of cardiovascular death,
secretion

nonfatal myocardial infarction, or nonfatal stroke

Occurrence of the individual components of the


primary composite cardiovascular outcome.
Fatal and nonfatal myocardial infarction
Fatal and nonfatal stroke
Death from any cause
Hospitalization for heart failure.

Method
Additional prespecified outcome:
changes in the glycated hemoglobin level and the
eGFR
initiation of additional antihyperglycemic agents or
suppressing long-term
glucagon insulin therapy
frequency
of severe insulin
hypoglycemia.
levels andincreasing
endogenous
secretion

Results
Study Patients
Glycemic Control
\

Primary Cardiovascular Outcome


Secondary Cardiovascular
Outcome
Hospitalization for Heart Failure
Death from Any Cause

Results

(Glycemic Control)

suppressing glucagon
levels and increasing endogenous insulin
secretion

Sitagliptin group:
Fewer additional antihyperglycemic agents
Less likely to start long-term insulin therapy

overall leastsquares mean


difference of
0.29%

Results
(Primary CV
Outcome)

suppressing glucagon
levels and increasing endogenous insulin
secretion

Results
(Secondary CV
Outcome)

suppressing glucagon
levels and increasing endogenous insulin
secretion

Results

(Hospitalization for
HF)

suppressing glucagon
levels and increasing endogenous insulin
secretion

Results

(Death from Any


Cause)

suppressing glucagon
levels and increasing endogenous insulin
secretion

Conclusio
Sitagliptin may be used in a diverse
n

group of patients with type 2 diabetes


who are at high cardiovascular risk
without increasing rates of cardiovascular
complications.
suppressing
glucagon
levels and increasing endogenous insulin
secretion

Longer duration?
More complicated coexisting illness?

The addition of sitagliptin to


usual care did not have a significant
effect on
rates of major adverse
cardiovascular events or
hospitalization for heart failure.