Effects of Dapagliflozin, an SGLT2

Inhibitor, on HbA1c, Body Weight,

and Hypoglycemia Risk in Patients
With Type 2 Diabetes Inadequately
Controlled on Pioglitazone
Monotherapy

Annis Rakhmawati
Pembimbing: dr R. Bowo Pramono, SpPDKEMD

Identitas Jurnal
Judul : Effects of Dapagliflozin, an SGLT2
Inhibitor, on HbA1c, Body Weight, and
Hypoglycemia Risk in Patients With Type 2
Diabetes Inadequately Controlled on
Pioglitazone Monotherapy
Penulis : Julio rosenstock et al
Publikasi
2012

: Diabetes care, volume 35, july

INTRODUCTION
SGLT2 inhibitor hiperglycemia
induce mild osmotic diuresis and
urinary excretion of glucose caloric
elimination weight loss
Dapagliflozin, an SGLT2 inhibitor,
improved glycemic control in T2DM as
monotherapy & in combination with
metformin, SU, or insulin, but not yet with
a thiazolidinedione (TZD)

 Pioglitazone lowers glucose by

enhancing insulin sensitivity.
Safety concerns of fluid retention,
weight gain, CHF, bone fractures,
bladder cancer has limited its use as
second line therapy when metformin
is not tolerated or as triple oral
therapy

 Dapagliflozin glucosuria diuresis

& caloric loss concern of weight
gain & fluid retention/edema.
The aim to examine the safety and
efficacy of dapagliflozin as SGLT2
inhibitor, added on to pioglitazone in
T2DM inadequately controlled on
pioglitazone.

Subjects
Inclusion Criteria
18 y.o with fasting C-peptide 1.0 ng/mL and BMI
45.0
29 July 2008 and 4 July 2009. The study tookplace
at 105 sites in Argentina, Canada,India, Mexico,
Peru, Philippines, Taiwan,and US

Exclusion Criteria:

aspartate or alanine aminotransferase 2.5 times

total bilirubin 2.0 mg/dL,
Cr 2.0mg/dL
urine albumin/creatinine ratio 1,800 mg/g,
creatinine clearance 50 mL/min,
CHF cf III and IV

Methods
randomized, double blind, placebocontrolled, parallel group to examine
the safety & efficacy of dapagliflozin
added on to pioglitazone in T2DM
inadequately controlled on pioglitazone

 Treatment-naive patients or those

receiving metformin, SU, or TZD entered a
10-week pioglitazone dose-optimization
period with only pioglitazone.
They were randomized, along with patients
previously receiving pioglitazone 30 mg,
to 48 weeks of double-blind dapagliflozin
5mg (n = 141) or 10mg (n = 140) or
placebo (n = 139) every day plus openlabel pioglitazone.

 Primary end point changes from

baseline in HbA1c, FPG, PPG, body
weight at week 24 using ANCOVA
model

Result

Discussion
In this study, the addition of
dapagliflozin to pioglitazone lowered
HbA1c and weight gain in T2DM
inadequately controlled on
pioglitazone alone.
Dapagliflozin acts in the kidney by
inhibiting the reabsorption of glucose
FPG , PPG

 The glucosuria induced by SGLT-2

inhibition suspected leading to
hypoglycemia, UTIs, and genital
infections.
Hypoglycemia events were rare in
this study.

 Consistent with previous reports

genital infections were higher in patients
on dapagliflozin than on placebo.
None of these genital infections were
serious, and all responded to
antimicrobial treatment.
Dapagliflozin, acting as a mild diuretic,
mitigate the fluid retaining effects of
pioglitazone

Conclusion
The direct removal of glucose by
dapagliflozin complements the
insulin-sensitizing action of
pioglitazone

Critical Appraisal
Are the results Valid
1. Was the assignment of patients to treatments randomized? And
was the randomization list concealed? yes
2. Was follow-up of patients sufficiently long and complete? yes
3. Were patients analyzed in the groups which they were randomized?
yes
4. Were patients and clinicians kept blind to treatment? yes
5. Were the groups treated equally, apart from the experimental
treatment? yes
6. Were the groups similar at the start of the trial? yes

Are the valid results of this

randomized study important?
1. What is the magnitude of the treatment effect?
No data
2. How precise is this estimate of the treatment
effect? No data

Are these valid, important

results applicable to our
patient?

1. Is our patient so different from those in the

study that its results cannot apply? No
2. Is the treatment feasible in our setting? Yes
3. What are our patients potential benefits and
harms form the therapy?
Benefit: potential combination that balances
well the benefits and risks of therapy for T2DM.
Harm : Has not been proved as gold standard
therapy

Thank you