1. diabetes

Up date therapy DIABETES
MELITUS
Fokus januvia
Dr. Yoseph Chandra, MKes,
GEJALA, TANDA, DAN
PENATALAKSANAANYA

1. Epidemiology and Economic
Burden of Type 2 Diabetes

Diabetes: A Healthcare “Tsunami”
IDF Diabetes Atlas, 2015
Approximately
55% of total
diabetes
patients –
Western Pacific
and South East
Asia

Diabetes—a growing global epidemic
Diabetes* worldwide prevalence estimates, 2030: >550 million1
• All cases of diabetes, including type 1 and type 2 diabetes, and impaired glucose tolerance (IGT), in patients aged 20-79 years.
1. International Diabetes Federation. IDF Diabetes Atlas, 5th ed. Brussels, Belgium: International Diabetes Federation, 2011.
Of all cases
of diabetes,
90% are type 2
diabetes2
2030 prevalence1:
South East Asia: 121 million
Indonesia: 7,2 → 11,8 million
Diabetes* worldwide prevalence, 2011: ~360 million1
2030 prevalence estimates : >550 million1

2. Risk of Morbidity & Mortality
in Type 2 Diabetes

Type 2 diabetes significantly increases
risk of complications1,2
1. International Diabetes Federation. Time to Act. 2001. http://www.idf.org/webdata/docs/Diabetes%20and%20CVD.pdf. Accessed February 28, 2012.
2. Seaquist ER. Diabetes. 2010;59:4-5.

Komplikasi Diabetes Melitus pada
mata : Retinopati diabetik
NORMAL RETINOPATI

• Jelas merupakan penyakit
orang usia lanjut
• 75 % terjadi  65 th,
meningkat tajam
• Penyebab kematian
& kecacatan

Erection Hardness Score (EHS)
Adapted from: Goldstein I, et al. N Engl J Med. 1998;338:1397-1404.
Severe ED Moderate ED Mild ED No ED
Penis
membesar tapi
tidak keras
Penis keras,
tetapi tidak
cukup untuk
penetrasi
Cukup keras
untuk
penetrasi, tapi
tidak
maksimal
Sepenuh nya
keras &
tegang
Penis
membesar tapi
tidak keras
Penis keras,
tetapi tidak
cukup untuk
penetrasi
Cukup keras
untuk
penetrasi, tapi
tidak
maksimal
Sepenuh nya
keras &
tegang

Type 2 diabetes—CVD is a leading cause of death
Emerging Risk Factors Collaboration.
N Engl J Med. 2011;364(9):829-841.

3. Current Treatment & Multiple
Challenge of Type 2 Diabetes

Type 2 diabetes—increasingly challenging to control over
time
1. UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854-865. 2. Campbell W. Br J Cardiol. 2000;7(10):625-631. 3. Khatib OMN, ed. EMRO Technical
Publications Series 32. World Health Organization; 2006.

Type 2 diabetes—approximately one-half of patients
are uncontrolled
Wong ND, et al. Persistent undertreatment of cardiovascular risk factors among subjects with type 2 diabetes in the United States 2005-2006. Presented at: American
Diabetes Association 70th Scientific Sessions; June 25-29, 2010; Orlando, FL.

Achieving Type 2 Diabetes Goals Remains
a Challenge
36
aData from NHANES 1999–2010 included 2403 adults with type 2 diabetes; 531 adults were included from NHANES 2009-2010.
bBased on 254 adults from NHANES 2009-2010. Goals defined as A1C <7%; BP <130/80 mmHg; LDL-C ≤100 mg/dL; BMI <30 kg/m2.
T2D=type 2 diabetes; BP=blood pressure; LDL-C=low-density lipoprotein cholesterol; BMI=body mass index;
NHANES=National Health and Nutrition Examination Survey.
Wong ND et al. Diab Vasc Dis Res. 2013;10:505-513.
55%
A1C <7.0%
8%
A1C, BP, LDL-C,
and BMI goalsb
Percentage of Adults With T2D Achieving Treatment Goals
From 2009 to 2010a

Greater Challenge in low and middle countries1
37
1. Gomes MB, et al. Presented at 53rd EASD, 11-15 Sep 2017, Lisbon, Portugal
Note: Data are from a sub-cohort of patients (n = 6534) who had available data for all three parameters.
HbA1c, glycated haemoglobin; LDL-C, low-density lipoprotein cholesterol;
SBP, systolic blood pressure.
17.6%
A1C <7.0%
6.7%
A1C, BP, and LDL-C
In T2DM patient starting 2nd line treatment, Less than
30% achieve LDLD-C and SBP target1

38
Very poor glycaemic control
• Indonesian HbA1c is the highest
compare with other participant
countries in DISCOVER study,
even after initiating second line of
therapy (mean+SD = 9.2+2%)1,
almost 70% patient >8%).2
1. Wahono DS et al. 2nd ICE on IMERI, 7 November 2017, Jakarta, Indonesia
2. Ji L et al. 53rd EASD, 11–15 September 2017, Lisbon, Portugal.

Type 2 diabetes—increased HbA1c elevates
risk of complications
Diabetes-related
complications included:
● Fatal or nonfatal myocardial
infarction, stroke, or
microvascular disease
● Amputation or death from
peripheral vascular disease
● Heart failure
● Cataract extraction
Stratton IM, et al. BMJ. 2000;321:405-412.

Type 2 diabetes—poor glycemic control and CV risk
factors significantly increase cost of care
Gilmer TP, et al. Diabetes Care.
1997;20(12):1847-1853.

Type 2 diabetes—many therapies are associated with
weight gain over time1,2
1. Inzucchi SE, et al. ADA/EASD Position Statement. Diabetes Care. 2012;35:1-16. Epub 20 April 2012. 2. Mitri J, Hamdy O. Expert Opin Drug Saf. 2009;8(5):573-584.

Type 2 diabetes—visceral adipose tissue (VAT) is a
major cardiovascular risk factor
1. Carr DB, et al. Diabetes. 2004;53(8):2087-2094. 2. Eeg-Olofsson K, et al. Diabetologia. 2009;52(1):65-73. 3. De Koning L, et al. Eur Heart J. 2007;28(7):850-856.
3
3

The importance of reducing
HbA1c, weight, blood
pressure, and lipids

Type 2 diabetes—controlling multiple
parameters is essential
Incremental reductions sustained
over time in HbA1c and other
parameters can benefit the
physical health of patients with
type 2 diabetes1-5
1. Stratton IM, et al. BMJ. 2000;321:405-412. 2. Pi-Sunyer FX. Postgrad Med. 2009;121(5):94-107. 3. Williamson DF, et al. Diabetes Care. 2000;23(10):1499-1504. 4. Patel
A. Lancet. 2007;370(9590):829-840. 5. Pyǒrälä K, et al. Diabetes Care. 1997;20(4):614-620.

Type 2 diabetes—guidelines recommend managing
multiple parameters1-5
ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes; ESC=Task Force on Diabetes and Cardiovascular Diseases of the European Society of
Cardiology; AACE=American Association of Clinical Endocrinologists; CDA=Canadian Diabetes Association; WHO=World Health Organization.
1. Guidelines for the prevention, management and care of diabetes mellitus. Cairo, Egypt, World Health Organization, 2006. 2. The Task Force on Diabetes and Cardiovascular
Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007;28:88-136.
3. American Diabetes Association. Diabetes Care. 2012;35(suppl 1):S4-S10. 4. Handelsman Y, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical
Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17(suppl 2):1-53. 5. Canadian Diabetes Association Clinical Practice Guidelines Expert
Committee. Can J Diabetes. 2008;32(suppl 1):S1-S201. 6. Inzucchi SE, et al. ADA/EASD Position Statement. Diabetes Care. 2012;35:1-16.
Although the EASD and ADA Guidelines each set forth specific HbA1C target goals, an ADA/EASD Joint Position
Statement on management of hyperglycemia (2012) recommends that treatment targets be individualized.6

Type 2 diabetes—LOWERING HbA1c reduces risk for macro-
and microvascular complications
Stratton IM et al. BMJ. 2000;321:405-412.

Type 2 diabetes—WEIGHT LOSS is associated with
decreased mortality
Author/Editor: David F. Williamson. Copyright 2000 American Diabetes Association. From Diabetes Care, Vol. 23, 2000; 1499-1504.
Reproduced by permission of The American Diabetes Association.
Prospective analysis with a 12-year mortality follow-up (1959-1972) of 4,970 overweight people with diabetes.
Weight loss of 1 to 9 lbs
is associated with
decreased mortality rates

Type 2 diabetes—lowering BLOOD PRESURE reduces risk of
complications
Patel A et al; for the ADVANCE Collaborative Group. Lancet. 2007;370(9590):829-840.
P= 0.027
(95% CI 2 to 32%)
P= 0.020
(95% CI 41 to 453)
P= 0.42
(95% CI -10 to 20%)
P< 0.0001
(95% CI 15 to -27%)
P= 0.10
(95% CI -1 to 10%)

The need for a pathway that acts
independently of insulin in
type 2 diabetes

The Ominous Octet
Islet b-cell
Impaired
Insulin Secretion
Neurotransmitter
Dysfunction
Decreased Glucose
Uptake
Islet a-cell
Increased
Glucagon Secretion
Increased
Lipolysis
Increased Glucose
Reabsorption
Increased
HGP
Decreased
Incretin Effect

Insulin-dependent pathways: organs and tissues
1. DeFronzo RA. Med Clin N Am. 2004;88(4): 787-835. 2. Guyton AC. Textbook of Medical Physiology. 7th ed. Philadelphia, PA: WB Saunders Company; 1986. 3. Uldry
M, Thorens B. Eur J Physiol. 2004;447(5):480-489. 4. Guyton AC. Textbook of Medical Physiology. 11th ed. Philadelphia, PA: WB Saunders Company; 2006. 5. Drucker
DJ, Nauck MA. Lancet. 2006;368(9548):1696-1705. 6. Schirra J, et al. Gut. 2006;55(2):243-251.
Glucose levels are managed in the body partly by insulin-dependent
pathways involving multiple organs and tissues1-6
SU, DPP4
inh, Glinid
Metformin,
TZD
Metformin,
TZD
Metformin,
TZD
DPP4 inh

An insulin-independent pathway—renal SGLT21,2
1. Rajesh R, et al. Int J Pharma Sci Res. 2010;1(2):139-147. 2. Marsenic O. Am J Kidney Dis. 2009;53(5):875‐883.

The role of the renal SGLT
pathway in glucose balance

In normal renal glucose handling, 90% of glucose is
reabsorbed by SGLT21–4
SGLT, sodium-glucose co-transporter 2.
Adapted from: 1. Wright EM. Am J Physiol Renal Physiol 2001;280:F10–18; 2. Lee YJ, et al. Kidney Int Suppl 2007;106:S27–35; 3. Hummel CS, et al. Am J Physiol Cell Physiol 2011;300:C14–21;
4. Marsenic O. Am J Kidney Dis 2009;53:875–83.
Remaining
glucose is
reabsorbed by
SGLT1 (10%)
Majority of glucose
is reabsorbed by
SGLT2 (90%)
Proximal tubule
Minimal to
no glucose
excretion
SGLT2
Glucose
Glucose
filtration

FORXIGA inhibits SGLT2 and removes excess glucose
in the urine independently of insulin
*Increases urinary volume by only ~1 additional void/day (~375 mL/day) in a 12-week study of healthy subjects and patients with Type 2 diabetes.
FORXIGA®. Summary of product characteristics, 2015.
Reduced glucose
reabsorption
SGLT2
Increased urinary
excretion of excess
glucose (~70 g/day,
corresponding to
280 kcal/day*1)
Proximal tubule
Glucose
filtration
FORXIGA
SGLT2
Glucose
FORXIGA
• By inhibiting SGLT2, FORXIGA removes glucose and associated calories
• FORXIGA is >1400-times more selective for SGLT2 versus SGLT1
Increased urinary
excretion of excess
glucose (~70 g/day,
corresponding to
280 kcal/day*)

FORXIGA lowers HbA1c with the additional benefits of
weight loss and blood pressure reduction1
FORXIGA is not indicated for the management of obesity or high blood pressure.1 Weight change was a secondary endpoint in clinical trials.1,3
*Increases urinary volume by only ~1 additional void/day (~375 mL/day) in a 12-week study of healthy subjects and patients with Type 2 diabetes.1
1. FORXIGA®. Summary of product characteristics, 2014;
2. Calories per hour.com. Available at: http://www.caloriesperhour.com/tutorial_pound.php. Last accessed August 2014;
Glycaemic control
FORXIGA:1
• Acts independently of
insulin mechanisms to
reduce HbA1c via the
kidney
• Has a low propensity for
hypoglycaemia
Weight loss
• Urinary excretion of ~70 g
glucose/day with
FORXIGA corresponds to
loss of 280 Kcal/day*1
(1 g glucose = ~4 Kcal)
• 1 lb of body fat equates to
~3500 calories2
• FORXIGA can result in
loss of 1 lb of body fat in
under 2 weeks
Blood pressure reduction
• FORXIGA increases
diuresis and is associated
with significant reductions
in systolic blood pressure1

Efficacy of FORXIGA (dapagliflozin)

Consistent Decreases in Fasting Plasma Glucose
at 24 weeks1,2,3
-35
-30
-25
-20
-15
-10
-5
0
-5.4 mg/dl
-28.8 mg/dl
-1.8 mg/dl
-28.8 mg/dl
-5.4 mg/dl
10 mg Placebo10 mg Placebo
p< 0.0001 p< 0.0001
Add On to Metformin1 Add On to Sulfonilurea2 Add On to TZD3
-23.4 mg/dl
1. Bailey CJ, et al. Lancet 2010;375:2223-33;
2. Strojek K, et al. Diabetes Obes Metab 2011;13:928-38;
3. Rosenstock J, et al. Diabetes Care, Volume 35, July 2012
FPGAdjustedmeanChangedfromBaseline
10 mg Placebo
p< 0.0001

Consistent Decreases Post Prandial Glucose after 2
hours at 24 weeks1,2
10 mg5 mg Pbo
n=141 n=140
n=139
1. Rosenstock J, et al. Diabetes Care, Volume 35, July 2012
2. Strojek et.al. Diabetes, Obesity and Metabolism 13: 928–938, 2011.
Add-on
to Pio1
Add on +
SU2
308 321.3
Forx 5 P=0.0007 vs plac
Forx 10 P<0.0001 vs plac
Both P<0.0001 vs plac

Consistent reductions in HbA1c in patients with
baseline HbA1c ≥9%
NR, not reported.
1. Katz A, et al. Diabetes 2014;63(Suppl. 1):A284. 2. Henry R, et al. 71st ADA Scientific Sessions, San Diego, 24-28 June, 2011 Abstract 307-OR
FORXIGA
Placebo
(24 weeks)
Add on to
Met XR2
-1.98
-1.44
9.05%
Add on to
metformin1
Add on to
SU1

-1.0
-0.8
-0.6
-0.4
-0.2
0.0
0.2
FORXIGA: Reductions in HbA1c were sustained over time
Data are mean change from baseline after adjustment for baseline value. Data after rescue are excluded. Analyses were obtained by longitudinal repeated measures analyses.
CI, confidence interval.
1. Bailey CJ, et al. Bailey et al. BMC Medicine 2013, 11:43.
Adjustedmeanchangefrom
baselineHbA1c(%)
Study week
+0.02%
(95% Cl,
–0.20 to –0.23%;
n=57)
–0.78%
(95% Cl,
–0.97 to –0.60%;
n=57)
FORXIGA 10 mg + metformin
(Mean baseline HbA1c 7.95%)
Placebo + metformin
(Mean baseline HbA1c 8.13%)
0 102
(n=133)
(n=132)
–0.80%
difference
8 16 24 37 6350 76 89
Primary endpoint
24 weeks
P<0.0001

Additional Benefit of FORXIGA
(Weight Reduction, BP reduction & Waist Circumference)

FORXIGA Consistent reductions in Body Weight in patients
as add on therapy at 24 weeks
-2.86
-3.33
-2.26
-1.14
-0.89
-1.36
-0.72
1.64
24-wk add-on
to Met1
24-wk Dapa
+ Met XR4
24-wk add-on
to Glim2
24-wk add-on
to Pio3
* *
*
*
Forx 10 Placebo Forx 10 Placebo Forx 10 Placebo
*p <0.001 vs. comparator
Baseline
Weight 88kg 81.1kg 81.1kg 86.3kg
24-weekadjustedfrombaselineweight(kg)
Forx 10 Placebo
1Bailey CJ, et al. Lancet 2010;375:2223–2233;; 2Strojek K, et al. Diabetes Obes Metab 2011;13:928-938; 3Rosenstock J, et al. 71st ADA Scientific Sessions, San Diego,
24–28 June, 2011 [Abstract 0986-P]; 4Henry R, et al. 71st ADA Scientific Sessions, San Diego, 24-28 June, 2011 Abstract 307-OR.

FORXIGA: Additional benefit of weight loss sustained over
time1
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0
(n=400)
Mean baseline weight 88.4 kg
Glipizide + metformin
(n=401)
Mean baseline weight 87.6 kg
0 10452
Adjustedmeanchangefrom
baselineweight(kg)
+1.36 kg
(95% Cl,
0.88 to 1.84 kg;
n=211)
–3.70 kg
(95% Cl,
–4.16 to –3.24 kg;
n=234)
Study week
–5.06 kg difference
(95% Cl, –5.73 to –4.4 kg)
6 12 18 26 34 42 65 78 91
Data are adjusted mean change from baseline and 95% CI derived from a repeated measures mixed model.
1. Nauck MA, et al. Diabetes Care 2011;34:2015–22;

FORXIGA: Adjusted mean change in waist circumference
(cm) from baseline at Week 24
Baseline 104.5 Baseline 105.6
0
–0.5
–1
–1.5
–2
–2.5
–3
–3.5
Placebo + metformin
(n=91)
(n=89)
–0.99
–2.51*
Changeinwaistcircumference
(cm)(SE)
*p=0.0143.
SE, standard error.
Bolinder J, et al. J Clin Endocrinol Metab 2012;97:1020–31.

MR substudy: VAT and SAT at Week 24
–39.2
–121.4
–297.5 –306.4
-350
-300
-250
-200
-150
-100
-50
0
Meanchangefrombaseline(cm3)
MR, magnetic resonance; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.
Bolinder J, et al. J Clin Endocrinol Metab 2012;97:1020–31.
SAT volume (cm3)VAT volume (cm3)
FORXIGA 10 mg
+ metformin
Placebo
+ metformin
FORXIGA 10 mg
+ metformin
Placebo
+ metformin
P = 0.0084 P = 0.0385

• In a prespecified pooled analysis of 12 placebo-controlled studies, FORXIGA 10 mg
reduced systolic and diastolic blood pressure versus placebo at Week 241
FORXIGA: Reduction in blood pressure
-5.0
-4.0
-3.0
-2.0
-1.0
0.0
Systolic blood pressure Diastolic blood pressure
FORXIGA 10 mg Control groups Control groups
–4.4 mmHg
(n=949)
–0.9 mmHg
(n=1096)
–2.1 mmHg
(n=949)
–0.5 mmHg
(n=1096)
Meanchangein
bloodpressure(mmHg)
FORXIGA is not indicated for the management of high blood pressure. Mean seated systolic and diastolic blood pressure were based on a placebo-controlled, pooled analysis from the 24-week, short-term,
double-blind treatment period, including data after rescue. N is the number of subjects with non-missing baseline and Week 24 (last observation carried forward) values in the randomised full analysis set.
Change in blood pressure was primarily assessed as safety or exploratory efficacy endpoints in the Phase III clinical programme; therefore, the background antihypertensive medications were not controlled.
1. FORXIGA®. Summary of product characteristics. Bristol-Myers Squibb/AstraZeneca EEIG, 2012; 2. BMS/AZ data on file.
Baseline blood pressure2 126 mmHg 129 mmHg 77 mmHg 79 mmHg
FORXIGA 10 mg
P value is not obtain from citation source

Tolerability of FORXIGA (dapagliflozin)

FORXIGA: Safety and tolerability from a wide-ranging
clinical programme
System organ class
Very common
(1/10)
Common*
(1/100 to <1/10)
Uncommon†
(1/1000 to <1/100)
Infections and infestations Vulvovaginitis, balanitis and
related genital infections‡
UTIs§
Fungal infection
Metabolism and nutrition disorders Hypoglycaemia (when
used with a SU or insulin)
Volume depletion||
Thirst
Nervous system disorders Dizziness
GI disorders Constipation
Dry mouth
Musculoskeletal and connective
tissue disorders
Back pain
Renal and urinary disorders Dysuria
Polyuria¶
Nocturia
Renal impairment
Reproductive system and breast
disorders
Vulvovaginal pruritus
Pruritus genital
Investigations Haematocrit increased**
Creatinine renal clearance
decreased
Dyslipidaemia††
Blood creatinine increased
Blood urea increased
Weight decreased
Footnotes are available in the slide notes.
GI, gastrointestinal; SU, sulphonylurea; UTI, urinary tract infection.
FORXIGA®. Summary of product characteristics, 2015.
• The safety of FORXIGA 10 mg was assessed in a pooled analysis of 13 placebo-controlled studies in
>2300 patients
Adverse reactions in placebo-controlled studies of FORXIGA (24-week data regardless of glycaemic rescue)

UTIs and genital infections
• Most genital infections* and UTIs were mild to moderate in intensity, rarely led to
discontinuation of FORXIGA and were generally resolvable with
a single course of standard treatment1
• Pyelonephritis was uncommon and occurred at a similar frequency to control1
*Genital infection includes the preferred terms: Vulvovaginal mycotic infection, vaginal infection, balanitis, genital infection fungal, vulvovaginal candidiasis, vulvovaginitis, balanitis candida,
genital candidiasis, genital infection, genital infection male, penile infection, vulvitis, vaginitis bacterial and vulval abscess.
1. FORXIGA®. Summary of product characteristics, 2014; 2. EMDAC background document. Available
at:http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm378079.pdf. Last accessed September 2014;

FORXIGA as add-on to metformin versus SU:
Lower risk of hypoglycaemia at 4 years
Del Prato S, et al. Presented at the 73rd American Diabetes Association Scientific Sessions, Chicago, USA. 21–25 June 2013. Abstract 62-LB.
Patientswith≥1episode
ofhypoglycaemia(%)
208 weeks
51.5%
(n=408)
5.4%
(n=406)
FORXIGA 10 mg
+ metformin
Glipizide
+ metformin
~10X
lower
incidence
0
10
20
30
40
50
60
70
80
90
100

For HCP Only
Current CVOT results among Glucose lowering therapies other
than SGLT2i
91
Study Anti-diabetic Drug HR p-value
TZD PROACTIVE1 Pioglitazone 0.90 (CI 0.80–1.02) NS
Insulin ORIGIN2 Insulin Glargine 1.02 (CI 0.94–1.11) NS
DPP4i
SAVOR2 Saxagliptin 1.00 (CI 0.89–1.12) NS
EXAMINE2 Alogliptin 0.96 (CI 0.80–1.15) NS
TECOS2 Sitagliptin 0.98 (CI 0.89–1.08) NS
GLP1RA
ELIXA2 Lixisenatide 1.02 (CI 0.89–1.17) NS
LEADER3 Liraglutide 0.87 (CI 0.78–0.97) 0.038*
SUSTAIN 6 Semaglutide 0.74 (CI 0.58–0.95) 0.02**
1. Dormandy JA, Charbonnel B, Eckland
DJ, et al. Lancet. 2005;366:1279–1289.
2. Schernthaner G, Schernthaner GH. Herz.
2016; 41: 208–216
3. Marso S. LEADER Cardiovascular
Outcomes. Presented at ADA 76th, June
13 2016, New Orleans, LA, USA.
4. Marso S et al. N Engl J Med
375(19):1834-1844: 2016
* >80% with established CVD; ** only established CVD included

CV events was lower in FORXIGA compared to placebo
Based on meta-analysis study
• A meta-analysis of CV events among 21 Phase IIb/III trials, showed no increase in the primary CV composite endpoint
of CV death, stroke, MI and hospitalisation for unstable angina with FORXIGA1,2
CV events were adjudicated by an independent committee.
CV, cardiovascular; HR, hazard ratio; MACE, major adverse cardiovascular event; MI, myocardial infarction; UA, unstable angina.
1. EMDAC background document. Available at:
http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm378079.pdf. Last accessed September 2014;
2. FORXIGA®. Summary of product characteristics, 2014.
FORXIGA
Control

For HCP Only
93
Dapagliflozin is associated with lower risk of hospitalization
for heart failure, major adverse cardiovascular events and
all-cause death compared to DPP-4i in T2D patients: CVD-
REAL Nordic
Norhammar A, Bodegard J, Nystrom, T, Nathanson D, Gulseth HL, Thuresson M,
Fenici P, Eriksson JW and Birkeland K
Poster (P3008) presented at European Society of Cardiology - Heart Failure
meeting; April 29 – May 2, 2017; Paris, France.

FORXIGA as add on to
metformin delivers significant
and sustained reductions in:1,2
 PPG, FPG & HbA1c,
Wth ADDITIONAL Benefit
Reduction1 :
 Weight
 Blood pressure
 Waist Circumference
 Uric acid
 CVD
 HIPOGLIKEMIA
FORXIGA: For your patients who are uncontrolled on
metformin with sufficient renal function
FORXIGA is not indicated for the management of obesity or high blood pressure.1 Weight change was a secondary endpoint in clinical trials.1,2
1. FORXIGA®. Summary of product characteristics, 2014; 2. Bailey CJ, et al. Lancet 2010;375:2223–33; 3. Jabbour SA, et al. Diabetes Care 2014;37:740–50;
As FORXIGA has an Insulin Independent
Pathway it may also be used to complement
other medications across the spectrum of
disease3
Early disease Advanced disease

FORXIGA: Other selected adverse events
ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase.
1. EMDAC background document. Available at:
http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm378079.pdf. Last accessed September 2014.
2. FORXIGA®. Summary of product characteristics, 2015.
Adverse event Details
Serum electrolytes FORXIGA has no clinically relevant impact on serum electrolytes1
• No increased risk of hyperkalaemia with FORXIGA
Lipids Small mean changes from baseline in fasting lipid levels were observed
with FORXIGA 10 mg1
Haematocrit Small dose-dependent changes from baseline were observed in the
haematocrit (up to 2.32% mean increase for FORXIGA 10 mg)1
• Caution in patients with already elevated haematocrit is warranted2
Hepatic safety No mean increases from baseline or imbalances in liver laboratory tests
for FORXIGA versus control1
• The proportion of patients with elevated laboratory values for ALT,
AST, total bilirubin and ALP was similar in the FORXIGA and
control groups1
Bone fractures The proportions of patients with fractures were small and balanced for
FORXIGA versus placebo1
Drug-to-drug
interactions
No known clinically relevant drug-to-drug interactions with FORXIGA2
Please see full prescribing information for adverse event data.

Events of volume depletion* were infrequent but more
common in patients treated with FORXIGA than placebo
• Serious events occurred in <0.2% of patients and were comparable between groups2
• Urinary volume increases were sustained at 12 weeks and amounted to approximately 375 mL/day1
(approximately equivalent to a can of soft drink)
*Including dehydration, hypovolaemia or hypotension.
1. FORXIGA®. Summary of product characteristics, 2014; 2. EMDAC background document. Available at: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/
drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm378079.pdf. Last accessed September 2014.
Placebo-controlled pool
(short term)1,2
Placebo-controlled pool
(short term + long term)2
FORXIGA
10 mg
Placebo
FORXIGA
10 mg
Placebo
Events, n (%)
N=2360
27 (1.1)
N=2295
17 (0.7)
N=2026
38 (1.9)
N=1956
27 (1.4)
FORXIGA is not recommended for initiation of therapy in patients who are volume depleted. Elderly patients may be at a greater
risk for volume depletion and are more likely to be treated with diuretics. In subjects ≥65 years of age, a higher proportion of
subjects treated with FORXIGA had adverse reactions related to volume depletion. Therapeutic experience in patients 75 years
and older is limited. Initiation of FORXIGA therapy in this population is not recommended. Temporary interruption of FORXIGA is
recommended for patients who develop volume depletion until the depletion is corrected.1,2

Datang pada tanggal 3 Februari 2016
Nama / inisial : Tn. H
Umur : 60 tahun
Jenis Kelamin : Laki - laki

Anamnesis
 Pasien datang dengan hasil laboratorium 2 bulan lalu
GDS 240mg/dl serta A1C 7,8, minum herbal untuk
diabetesnya

Phsical examination and laboratoty test :
 GDS : 240 mg/dl
 A1C : 7,8
 TD : 130 / 80
 Pulse : 92x / menit
 BB : 80 kg
 TB : 165 cm

Diagnosis
 T2DM tidak terkontrol
Overweight

Medication and Follow up treatment
Glucophage XR – 1x750
Forxiga 1 x 10mg
Kontrol tanggal 13 Februari 2016
• GDS : 125 mg/dl
• BB : 79 kg
• TD : 120 / 80
• Tidak ada keluhan, terapi dilanjutkan
Kontrol tanggal 23 Februari 2016
• GDS : 116 mg/dl
• BB : 77 kg
• TD : 120 / 80
• Tidak ada keluhan, terapi dilanjutkan

1. diabetes

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