When Time Meets Power :

Time to Benefit

Wira Gotera

For healthcare professionals only

SC-ID-01793
The cardio-renal-metabolic (CRM) systems are
interrelated
The heart is the most “metabolically demanding”
organ, susceptible to changes in volume
and metabolism1,2

Regulation of energy
metabolism by liver, pancreas
The kidneys play a key role in
and fat is essential for healthy
glucose and volume homeostasis,
function of organs, especially
and blood pressure regulation5,6
the heart and kidneys1–4

CRM, cardio-renal-metabolic
1. Lopashuk GD & Ussher JR. Circ Res 2016;119:1173; 2. Song MK et al. J Diabetes Res.2014;2014:e313718. 3. Connell AW et al. J Am Soc Hypertens 2014;8:604; 4. de Boer IH &
Utzschneider KM. Nephrol Dial Transplant 2017;32:588; 5. García-Donaire JA & Ruilope LM. Int J Nephrol 2011;2011:975782; 6. Alsahli M & Gerich JE Diabetes Res Clin Pract 2017;133:1
The CRM systems

The CRM systems are interrelated; acute or chronic

dysfunction in the heart, kidneys or metabolic system may
induce dysfunction in the other1–4

Each dysfunctional organ has the ability to initiate and

perpetuate disease in the other organs through
haemodynamic, neurohormonal and
immunological/biochemical feedback pathways1,2

T2D is a risk factor for diseases related to the cardiac and

renal systems3

CRM, cardio-renal-metabolic
1. Song MK et al. J Diabetes Res 2014;2014:e313718; 2. Rangaswami J et al. Circulation 2019;139:e840; 3. House AA et al. Kidney Int 2019;95:1304; 4. Raghavan K et al. Cardiorenal Med
2019;9:240
 PATOFISIOLOGI GANGGUAN CARDIOVASKULAR

Cardiomiocyte/mbr Basalis
Hubungan antara Albumin Creatinin Ratio (ACR, mcg/gram) dengan
global longitudinal strain (%), r 0,57, r² 0,33, p < 0,001.

Gotera, Penelitian Residen PJT RSUP Sanglah 2019

Since 2016, guidelines and societies have been recommending the
use of SGLT2 inhibitors and/or GLP-1 receptor agonists for their
CRM benefits
…2015 2016 2018 2019 2020
Independent of HbA1c;
Glycaemic CV and mortality Benefits in Nephroprotection in
ASCVD, HF or CKD
control1,2 benefits ASCVD and chronic HF7 T2D + CKD + DKD
predominates10

ADA/EASD: CDA: Empagliflozin ADA: recommended

ERA–EDTA and ESC/EASD
SGLT2 inhibitors recommended to reduce GLP-1 RAs or SGLT2
ADA: Empagliflozin and recommended use of SGLT2
and GLP-1 RAs the risk of CV and inhibitors with proven CVD
canagliflozin recommended inhibitors with evidence for
recommended as all-cause mortality (Feb)3 benefit if ASCVD
as agents with proven benefit cardio- and nephroprotection;8
glucose-lowering predominates
ESC: Empagliflozin on MACE and CV death; to reduce progression of DKD9
agents only liraglutide has
recommended to prevent or SGLT2 inhibitors with evidence
delay the onset of HF and ASCVD benefit only Use GLP-1 RAs if
of reducing HF and/or CKD if
prolong life (May)4,5 SGLT2 inhibitors not tolerated8
HF or CKD predominates
CDA: Liraglutide
recommended to reduce
the risk of MACE (Sep)6

For full recommendations, please refer to the individual references and guidelines or the AT2D module ‘Evolving evidence-based recommendations in T2D’
ADA, American Diabetes Association; ASCVD, atherosclerotic cardiovascular disease; CDA, Canadian Diabetes Association; CRM, cardio-renal-metabolic; DKD, diabetic kidney disease;
EASD, European Association for the Study of Diabetes; ERA-EDTA, European Renal Association-European Dialysis and Transplant Association; ESC, European Society of Cardiology;
GLP-1 RA, glucagon-like peptide-1 receptor agonist; HHF, hospitalisation for heart failure
See slide notes for full list of references
Kasus 1
• SD, 57 thn, DM 2 tahun dengan kontrol teratur,.
• Terapi, Metformin 3x500 mg, Olah raga teratur, diet sesuai anjuran
2000 kkal/hari
• Saat datang , PF, TD 140/85 mgHg, GD acak 220 mg%
• Lab , GD puasa 182 mg%, HbA1c 8,2%, LDL 123 mg%, TGA 187mg%
• SC 0,82 mg%, Albuminuria(-), Keton (-), ECG dbn
Kasus 2
• Laki, SD, 32 thn, Baru tahu DM saat periksa lab.
• 3P (+), Lemas
• PF, IMT 30 , TD 120/80 lain dbn
• Lab GDF 302, HbA1c 12,3 LDL 90, TGA 96,
• UL, keton (-), Glucosa (+3)
Patients with T2D have multiple risk factors that
contribute to CRM diseases

CV disease/
• ~55% of patients with HF • T2D further reduces life
T2D have NAFLD1 expectancy in patients
• Over half of patients with cardio–renal
with T2D are reported comorbidities3,4
to be obese2
• T2D reduces life
T2D CKD
expectancy by
~6 years*3

*Average for men and women aged 60 years

CRM, cardio-renal-metabolic; NAFLD, non-alcoholic fatty liver disease
1. Younossi ZM et al. J Hepatology 2019;71:793; 2. Masmiquel L et al. Cardiovasc Diabetol 2016;15:29; 3. The Emerging Risk Factors Collaboration. JAMA 2015;314:52; 4. Wen C et al.
Kidney Int 2017;92:388
Patients with T2D are at increased risk of complications
such as CV disease and HF

• Approximately one in
three patients with CV disease/
T2D has CV disease1 HF
• There is a 2- to 5-fold
increased risk of HHF*
in patients with T2D†2
• CV disease is the
leading cause of T2D CKD
mortality in patients
with T2D3,4

*Versus those without T2D; †Patients with T2D aged <55 years
HHF, hospitalisation for heart failure
1. International Diabetes Foundation. Diabetes Atlas 9th Edition. http://www.diabetesatlas.org (accessed June 2020); 2. Rosengren A et al. Diabetologia 2018;61:2300; 3. Morrish NJ et al.
Diabetologia 2001;44(Suppl. 2):S14; 4. Davies MJ et al. Diabetes Care 2018;41:2669
The presence of CKD increases the risk of CV morbidity
and mortality
• Up to 67% of patients
with HF are estimated to
CV disease/ have CKD1
HF • Risk of CV death
increases as kidney
function declines2
• Presence of CKD in
patients with HF
T2D CKD increases risk of mortality
by ~25–28%3

1. Sarraf M et al. Clin J Am Soc Nephrol 2009;4:2013; 2. Matsushita K et al. Lancet 2010;375:2073; 3. Ather S et al. J Am Coll Cardiol 2012;59:998
Patients with T2D are at increased risk of complications
such as CKD

• CKD affects up to 40% of

CV disease/ patients with T2D1,2
HF • Diabetes and/or hypertension
is the cause of >80% of
ESKD cases worldwide1
• Life expectancy is reduced in
patients with T2D and early
CKD by 16 years – 10 more
T2D CKD
years than CKD alone*3

*Average of men/women and compared with those without diabetes or CKD

ESKD, end-stage kidney disease
1. International Diabetes Foundation. Diabetes Atlas 9th Edition. http://www.diabetesatlas.org (accessed June 2020); 2. Umanath K & Lewis JB. Am J Kidney Dis 2018;71:884. 3. Wen C et al.
Kidney Int 2017;92:388
T2DM is a progressive disease requiring a multifaceted approach
to reduce risk factors

Goals in T2DM Management : Should be a combination of Intermediate and Ultimate Goals

Empagliflozin (SGLT-2i) addresses both the Intermediate

and Ultimate Goals in T2DM Management2

1. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care. 2016;39(suppl 1): S1-S2; 2. Informasi Produk local Jardiance. April 2020
Glucose urine excretion through SGLT-2 inhibition1,2

Glucose filtered
> 180 g/ day

SGLT2
SGLT2
inhibitor

SGLT2 inhibitors decrease

glucose reabsorption in proximal
SGLT1 tubule, causing
glucose excretion in urine and
diuresis.

SGLT, sodium glucose co-transporter.

*Loss of ~ 80 g of glucose/day = 320 calories/day.
1. Gerich JE. Diabet Med. 2010;27:136–142. 2. Bakris GL, et al. Kidney Int. 2009;75;1272–1277.
 • Inclusion criteria:
– Adults with type 2 diabetes
– BMI ≤45 kg/m2
The first SGLT-2 Inhibitor CVOT. – HbA1c 7–10%*
– Established cardiovascular disease:
All patients received standard of care for glucose control and CV risk • History of MI •CABG
reduction, including RAAS inhibition and lipid-lowering agents. • CAD •History of Stroke
Stable background glucose-lowering Background glucose-lowering medication adjustment • Multi-vessel CAD •PAD
therapy (first 12 weeks) allowed to achieve glycaemic control • Single-vessel CAD •HF
• Exclusion criteria:
Multifactorial CV risk reduction
– eGFR <30 mL/min/1.73m2 (MDRD)

Placebo
(n=2333)
Primary endpoint: 3P-MACE

Randomised
Secondary endpoint: 4P-MACE
Empagliflozin 10 mg
and treated
(n=2345) Further pre-specified endpoints:
(N=7020) Pooled
- CV death -Non-fatal MI
Empagliflozin 25 mg
(n=2342) - HHF -Non-fatal Stroke
- All-cause mortality
Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in combination
with: Metformin, Metformin and a sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study
results with respect to combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions for use, Interaction with
other medicinal products and other forms of interactions, and Pharmacodynamics properties.
CV, cardiovascular; RAAS, renin–angiotensin–aldosterone system; T2D, type 2 diabetes
BMI, body mass index; eGFR, estimated glomerular filtration rate; MDRD, Modification of Diet in Renal Disease
*No glucose-lowering therapy for ≥12 weeks prior to randomisation or no change in dose for ≥12 weeks prior to randomisation or, in the case of insulin, unchanged by >10% compared to the
dose at randomisation
Zinman B et al. N Engl J Med 2015;373:2117; Zaman B et al. Cardiovasc Diabetol 2014;13:102
 EMPA-REG OUTCOME®
CVOT of Empagliflozin, the first to show significance in reduction of CV outcomes.
3P-MACE CV Death

↓ 14% ↓ 38%

HHF All Cause Mortality

↓ 35% ↓ 32%

Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in combination with: Metformin, Metformin and a
sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study results with respect to combination, effects on glycemic control and
cardiovascular events, and the populations studied, see sections Special warnings and precautions for use, Interaction with other medicinal products and other forms of interactions, and Pharmacodynamics properties.
Zinman B et al. N Engl J Med 2015;373:2117
CV Outcomes in SGLT-2 Inhibitors CVOTs

All-cause Renal
3P-MACE CV Death HHF
mortality Endpoints

EMPA-REG Outcome HR 0.86 HR 0.62 HR 0.65 HR 0.68 HR 0.61

(Empagliflozin) (0.74-0.99) (0.49-0.77) (0.50-0.85) (0.57-0.82) (0.53-0.70)

CANVAS Program HR 0.86 HR 0.87 HR 0.67 HR 0.87 HR 0.60

(Canagliflozin) (0.75-0.97) (0.72-1.06) (0.52-0.87) (0.74-1.01) (0.47-0.77)

DECLARE-TIMI 58 HR 0.93 HR 0.98 HR 0.73 HR 0.93 HR 0.53

(Dapagliflozin) (0.84-1.03) (0.82-1.17) (0.61-0.88) (0.82-1.04) (0.43-0.66)

VERTIS CV HR 0.97 HR 0.92 HR 0.70 HR 0.93 HR 0.81

(Ertugliflozin) (0.85-1.11) (0.77-1.11) (0.54-0.90) (0.80-1.08) (0.63-1.04)

Superior Non-inferior
Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in combination with:
Metformin, Metformin and a sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study results with
respect to combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions for use, Interaction with other medicinal
products and other forms of interactions, and Pharmacodynamics properties. CV, cardiovascular; HHF, hospitalization for heart failure; MACE, major adverse cardiovascular events.
1. Zinman B et al. N Engl J Med 2015;373:2117 (supplemental appendix); 2. Wiviott S et al. N Engl J Med 2018;DOI: 10.1056/NEJMoa1812389; 3. Neal B et al. N Engl J Med 2017;377:644
(supplementary appendix); 4. Cannon CP et al. N Engl J Med 2020;383:1425-35
How is the effect of Empagliflozin in Insulin use?
A Post hoc Observation from the EMPA-REG OUTCOME® Trial (ADA June 2020)
Empagliflozin sustained new Insulin initiation among
Insulin-naïve patients
Placebo Pooled Empagliflozin
4 years
20 19.6%
3 years

Probability of new insulin initiation, %

17.6%
HR 0.40
15 (95% CI 0.32, 0.49) 2 years
p<0.0001 12.7%

10 1 year
7.0%
4 years
3 years 8.5%
5 7.5%
2 years
1 year 5.0%
0 2.8%
0 180 360 540 720 900 1080 1260 1440

No. of participants Day since first medication intake

Placebo 1198 1132 1084 1010 888 659 550 364 86
Empagliflozin 2435 2370 2306 2234 2002 1458 1251 872 220

Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in combination with:
Metformin, Metformin and a sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study results with
respect to combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions for use, Interaction with other
medicinal products and other forms of interactions, and Pharmacodynamics properties.
Outcome of sustained insulin initiation was defined to be maintained on ≥2 consecutive visits ≥13 weeks apart.
Cox regression model adjusted for baseline HbA1c, time since T2D diagnosis, BMI, eGFR, geographic region and treatment status Kaplan-Meier estimates.
BMI, body mass index; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin; T2D, type 2 diabetes.
Vaduganathan, M. et al. Presented at the American Diabetes Association Scientific Sessions 2020, June 12-16, 2020.
Empagliflozin sustained total daily Insulin dose increase
by > 20% among Insulin-treated patients
Placebo Pooled Empagliflozin
40 HR 0.42 4 years
(95% CI 0.36, 0.49) 3 years 34.7%
35
31.3%

Probability of >20% insulin

p<0.0001
30 2 years

dose increase, %
24.3%
25
1 year
20 13.1%

15 4 years
3 years 18.3%
10 15.5%
2 years
5 9.9%
1 year
0 4.5%
0 500 1000 1500
No. of participants Day since first medication intake
Placebo 1135 877 412 4
Empagliflozin 2252 2016 1061 23

Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in combination
with: Metformin, Metformin and a sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study
results with respect to combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions for use, Interaction with
other medicinal products and other forms of interactions, and Pharmacodynamics properties.
Outcome of sustained insulin dose increase was defined to be maintained on ≥2 consecutive visits ≥13 weeks apart.
Cox regression model adjusted for baseline HbA1c, time since T2D diagnosis, BMI, eGFR, geographic region and treatment status Kaplan-Meier estimates.
BMI, body mass index; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin; T2D, type 2 diabetes.
Vaduganathan, M. et al. Presented at the American Diabetes Association Scientific Sessions 2020, June 12-16, 2020.
How Early After Treatment Initiation are the
CV Benefits of Empagliflozin Apparent?
A Post hoc Observation from the EMPA-REG OUTCOME® Trial (ADA June 2020)
Time to CV death
16

empagliflozin vs placebo
First 360 days Day 317
4
Day 59
Hazard ratio (95% CI)

HR 0.60
HR 0.28 (95% CI 0.37, 0.98)
(95% CI 0.08, 0.96) p=0.0409
1

0.25

0.0625

0 30 60 90 120 150 180 210 240 270 300 330 360

Censoring relative to randomization (days)

Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in
combination with: Metformin, Metformin and a sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic
control. For study results with respect to combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions
for use, Interaction with other medicinal products and other forms of interactions, and Pharmacodynamics properties.
Cox regression for time to CV death, pooled empagliflozin versus placebo. Hazard ratios and 95% confidence intervals (CI) are shown in relation to time point of censoring – treated set.
CV, cardiovascular
https://www.usscicomms.com/sites/default/files/ADA_2020_ERO_Time_to_benefit_Verma_FINAL.pdf.
Time to first HHF
16

Day 17
empagliflozin vs placebo
4 HR 0.10 First 100 days
(95% CI 0.01, 0.87)
Hazard ratio (95% CI)

p=0.0372
1

0.25

0.0625

0.0156

0 10 20 30 40 50 60 70 80 90 100

Censoring relative to randomization (days)

Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in combination
with: Metformin, Metformin and a sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study
results with respect to combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions for use, Interaction with
other medicinal products and other forms of interactions, and Pharmacodynamics properties.
Cox regression for time to first HHF, pooled empagliflozin versus placebo. Hazard ratios and 95% confidence intervals (CI) are shown in relation to time point of censoring – treated set.
HHF, hospitalization for heart failure.
1. Fitchett D et al. Eur Heart J 2018;39;363; 2. https://www.usscicomms.com/sites/default/files/ADA_2020_ERO_Time_to_benefit_Verma_FINAL.pdf
Time to first HHF or CV death
16

empagliflozin vs placebo
Day 27 First 100 days
4 HR 0.28
Hazard ratio (95% CI)

(95% CI 0.08, 0.97)

p=0.0445

0.25

0.0625

0 10 20 30 40 50 60 70 80 90 100

Censoring relative to randomization (days)

Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in combination with:
Metformin, Metformin and a sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study results with
respect to combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions for use, Interaction with other
medicinal products and other forms of interactions, and Pharmacodynamics properties.
Cox regression for time to first HHF or CV death (excluding fatal stroke), pooled empagliflozin versus placebo. Hazard ratios and 95% confidence intervals (CI) are shown in relation to time point
of censoring – treated set.
CV, cardiovascular; HHF, hospitalization for heart failure.
https://www.usscicomms.com/sites/default/files/ADA_2020_ERO_Time_to_benefit_Verma_FINAL.pdf
How is the latest guidelines affected throughout the world?
Updated information on guidelines
ADA Guidelines in 2021

Empagliflozin is indicated in adult patients with type

2 diabetes mellitus to improve glycemic control,
when metformin used alone does not provide
adequate glycemic control, in combination with:
Metformin, Metformin and a sulfonylurea, Metformin
and pioglitazone. When the existing therapy, along
with diet and exercise, does not provide adequate
glycemic control. For study results with respect to
combination, effects on glycemic control and
cardiovascular events, and the populations studied,
see sections Special warnings and precautions for
use, Interaction with other medicinal products and
other forms of interactions, and Pharmacodynamics
properties.

American Diabetes Association Diabetes Care 2021

Jan; 44(Supplement 1): S111-
S124.https://doi.org/10.2337/dc21-S009
ESC/EASD Guidelines in 2019

Empagliflozin is indicated in adult patients with type 2 diabetes

mellitus to improve glycemic control, when metformin used alone
does not provide adequate glycemic control, in combination with:
Metformin, Metformin and a sulfonylurea, Metformin and
pioglitazone. When the existing therapy, along with diet and
exercise, does not provide adequate glycemic control. For study
results with respect to combination, effects on glycemic control
and cardiovascular events, and the populations studied, see
sections Special warnings and precautions for use, Interaction
with other medicinal products and other forms of interactions, and
Pharmacodynamics properties.
SGLT2, sodium-glucose co-transporter-2; HHF, Hospitalization
for Heart Failure; T2DM, Type 2 Diabetes Mellitus; CVD,
Cardiovascular Disease
2019 ESC Guidelines on diabetes, pre-diabetes, and
cardiovascular diseases developed in collaboration with the
EASD 2019
ESC/EASD Guidelines in 2019

Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in combination
with: Metformin, Metformin and a sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study
results with respect to combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions for use, Interaction with
other medicinal products and other forms of interactions, and Pharmacodynamics properties.
SGLT2, sodium-glucose co-transporter-2; HHF, Hospitalization for Heart Failure; T2DM, Type 2 Diabetes Mellitus; CVD, Cardiovascular Disease
1. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD 2019
KDIGO 2020 Guideline

Empagliflozin is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in
combination with: Metformin, Metformin and a sulfonylurea, Metformin and pioglitazone. When the existing therapy, along with diet and exercise, does not provide adequate glycemic
control. For study results with respect to combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions
for use, Interaction with other medicinal products and other forms of interactions, and Pharmacodynamics properties.

KDIGO Guidelines for Diabetes in CKD 2020

Algorithm of Type 2 Diabetes management in Indonesia (Perkeni, 2019)
GOAL THERAPY : HbA1c <7% (Individualised)

HEALTHY LIFESTYLE MODIFICATION

Entry HbA1c Entry HbA1c Entry HbA1c
<7.5% >7.5%-9% >9%

MONOTHERAPY DUAL THERAPY SYMPTOMS

(combination of 2 TRIPLE THERAPY
Metformin drugs with different (combination of 3 drugs with NO YES
mechanism) different mechanism)
GLP-1 RA
If not at DUAL

Metformin or other first line drug

GLP-1 RA GLP-1 RA INSULIN

Metformin or other first line drug

DPP-4i goal in 3 THERAPY
months, ±
AG-i proceed DPP-4i DPP-4i Other

Second line drugs

to DUAL If not at If not at OR Agents
SGLT-2i THERAP TZD goal in 3 TZD goal in 3
months, months, TRIPLE
Y proceed to
SGLT-2i SGLT-2i proceed to THERAPY
TZD TRIPLE
ADD OR
THERAPY
Basal INTENSIF
SU/GN (combinatio Basal Insulin
n of 3 Y Insulin
Insulin Therapy
drugs)
SU/GN
SU/GN ADD OR INTENSIFY
AG-i INSULIN
AG-i

1. Pemilihan dan penggunaan obat mempertimbangkan faktor pembiayaan, ketersediaan obat, efektifitas, manfaat kardiorenal, efek
samping, efek terhadap berat badan, serta pilihan pasien.
2. Pengelolaan bukan hanya meliputi gula darah, tetapi juga penanganan faktor – faktor resiko kardiorenal yang lain secara
terintegrasi.
3. Obat Agonis GLP-1 dan penghambat SGLT-2 tertentu menunjukkan manfaat untuk pasien dengan komorbid penyakit
kardiovaskular aterosklerotik, gagal jantung dan gagal ginjal. Kedua golongan obat ini disarankan menjadi pilihan untuk
pasien dengan komorbid/komplikasi penyakit tersebut.
4. Bila HbA1C tidak bisa diperiksa maka sebagai pedoman dipakai glukosa darah rerata yang dikonversikan ke HbA1C (poin 7
penjelasan algoritma).
Good News for Indonesian T2D Patients!
• BPOM approved in July 2020.
• Empagliflozin as the first SGLT-2
Inhibitor approved to reduce CV
BPOM approved CV benefit of Jardiance based on EMPA-REG OUTCOME events for T2DM patients with
INDICATIONS Cardiovascular Disease.
Add on combination:
JARDIANCE is indicated in adult patients with type 2 diabetes mellitus to
improve glycemic control, when metformin used alone does not provide
• The CV benefit of Jardiance refers
adequate glycemic control, in combination with:
Metformin
to landmark study EMPA-REG
Metformin and a sulfonylurea,
Metformin and pioglitazone,
OUTCOME.
When the existing therapy, along with diet and exercise, does not provide
adequate glycemic control • Currently Empagliflozin is also
For study results with respect to combination, effects on glycemic control and available in fixed dose combination
cardiovascular events, and the populations studied, see sections Special
warnings and precautions for use, Interaction with other medicinal products (FDC) on Metformin.
and other forms of interactions, and Pharmacodynamic properties

*Effect of Cardiovascular events refer to Cardiovascular Outcome of EMPA-REG OUTCOME Study (in Local
Product Information section Pharmacological properties )

Jardiance Local Product Information Jul 2020

Kasus 1
• SD, 57 thn, DM 2 tahun dengan control teratur,.
• Terapi, Metformin 3x500 mg, Olah raga teratur, diet sesuai anjuran
2000 kkal/hari
• Saat dating , PF, TD 140/85 mgHg, GD acak 220 mg%
• Lab , GD puasa 182 mg%, HbA1c 8,2%, LDL 123 mg%, TGA 187mg%
• SC 0,82 mg%, Albuminuria(-), Keton (-), ECG dbn
Kasus 1 (cont)
Terapi awal Kontrol minggu ke2 Kontrol minggu 6 Minggu ke 12

Emphaglifozin GD acak 145 mg% GDF 108 HbA1c 6,9%

metformin TD 130/80 GD P 138 TD 120/80
12,5/1000 OD TD 130/80 Gluc Urin (+4)
Atorvastatin 20 mg Keluhan (-)
OD
Kasus 2
• Laki, SD, 32 thn, Baru tahu DM saat periksa lab.
• 3P (+), Lemas
• PF, IMT 30 , TD 120/80 lain dbn
• Lab GDF 302, HbA1c 12,3 LDL 90, TGA 96,
• UL, keton (-), Glucosa (+3)
Kasus 2 (cont)
Initial terapi Kontrol pertama Kontrol minggu ke 12 Wa Terakhir
(10/1 2021) (10 hari) (29/4 2021)
Ideg Asp 12-0-12 Gd acak 168 HbA1c 7,0 GDF 89
Emphaglifozin 12,5/100 Terapi lanjut GDF 100 IdegAsp 8-0-6
OD Terapi Empha. Met terskan
Ideg Asp 12-0-10
Empha, met terskan
 Take Home Messages
1. Diabetes (DMT2)adalah penyakit Cardiovaskular
2. Dihubungkan dengan HF dan DKD (CRM),
3. Pendekatan Holistik dan berkesinambungan harus diterapkan sejak dini
4. Empagliflozin (Jardiance®) dalam study study ternyata memberikan efek
yang menjanjikan
5. Guidline dan Societies, saat ini sudah mengarah untuk mengatasinya
6. SGLT2-inh di Indonesia sudah di approved, untuk risiko CV pad DMT2
Terima Kasih n Suksme…