Extending the use of SGLT2i on

(and beyond) Diabetic Kidney Disease

Kandarini, Y
DISCLAIMER
• This event is a non-promotional event, sponsored by AstraZeneca
Indonesia which may contains off label information.
• During this event, data may refer to medicines or indications that may
not be approved in Indonesia. They are presented in the spirit of
education and the right of the scientific and medical community to be
fully informed concerning scientific and medical progress. The
information should under no circumstances be regarded as a
recommendation for use of the medicine or indication.

2
OUTLINE
 CKD Burden
• CKD is a major public health issue, with its prevalence and cost that are
projected to rise regardless of its etiology. This condition is worsen with
underdiagnose of CKD both globally and locally (Indonesian). And its
therapeutic innovation has been very limited within the last 20 years
 SGLT2 inhibitor in CKD
• SGLT2i shows hope in retarding the progression in Kidney Disease. What
are the mechanism?
 From Prevention to Treatment
• DECLARE TIMI 58 shows promise in preventing the progression of Kidney
Disease in Type 2 Diabetes Melitus patients. And DAPA CKD further
emphasize the benefit of SGLT2i in Renal outcome for patients
CKD Burden
SGLT2 inhibitor in CKD
From Prevention to Treatment
CKD is a major global public health crisis, and
its prevalence and cost are projected to rise

PREVALENCE AND COST

Up to a 16% increase in Up to a 23% increase in

prevalence2,3,a cost4,b

The global 2026 2026

prevalence of CKD
is >840 million1

2021 2021
a
Projected prevalence of CKD stage 1-5 per 100,000 people in France, Italy, Spain, UK, Australia, Brazil, Canada, China, Japan, and USA; bProjected annual costs of CKD and KRT in patients from USA, Australia, China, Japan, Belgium, Italy,
Spain, UK, Germany, Brazil, and Canada.
1. Jager KJ et al. Kidney Int. 2019;96(5):1048-1050; 2. Power A et al. Poster presented at: ISN-WCN (Virtual Meeting); April 15-19, 2021; 3. Tangri N et al. Poster presented at: ISN-WCN (Virtual Meeting); April 15-19, 2021; 4. Mennini FS et
al. Poster presented at: ISPOR Europe (Virtual Meeting); November 30-December 3, 2021.

5
Rates of CKD mortality and KRT are increasing worldwide

Rates of mortality and years of life lost due to The number of people undergoing KRT is
CKD increased over a 10-year period1,a expected to significantly increase by 20262,b,c

40%

34% 2026
Percentage change, 2007–2017

35%

30%

25% 21%
20%

2021
15%
Up to a 24%
increase
10%

5%

0%
Deaths Years of life lost
a
Deaths and years of life lost included patients of all ages; bProjected burden of KRT across Brazil, Canada, USA, UK, Germany, Italy, Belgium, Spain, China, Australia, and Japan; cKRT includes hemodialysis, peritoneal dialysis and kidney transplant.
1. GBD 2017 Causes of Death Collaborators. Lancet. 2018;392(10159):1736-1788; 2. Mennini FS et al. Poster presented at: ISPOR Europe (Virtual Meeting); November 30-
December 3, 2021.

6
 Diagnosis of CKD remains low

KDIGO Conference on Early Identification and

Intervention in CKD3

Up to 90% of patients with Select conclusions:

CKD stage 3 • Persons with hypertension, diabetes, or

CV disease should be screened for CKD
remain undiagnosed1,2 • CKD screening must consist of a dual
assessment of eGFR and UACR

Early identification and intervention in CKD is

essential to:4
• slowing progression of CKD
• substantially reducing morbidity and mortality
CKD = chronic kidney disease; CV = cardiovascular; eGFR = estimated glomerular filtration rate; KDIGO = Kidney Disease: Improving Global Outcomes;
UACR = urinary albumin:creatinine ratio.

1. Ravera M et al. Am J Kidney Dis. 2011;57:71-77; 2. Ryan TP et al. Am J Med. 2007;120:981-986; 3. Shlipak MG et al. Kidney Int. 2021;99:34-47.

7
7
CKD Diagnosis in Indonesia
• Earlier survey shows that 1 of 8 people in
Indonesia who had their creatinine measured had
CKD (eGFR ≤ 60 mL/min/ 1.73 m)
• Earlier survey showed 2.8% have persistent
proteinuria
• As high as 70% general population didn’t know
the risk factor of CKD

CKD : Chronic Kidney Disease

Prodjosuadji, et al Nephrology 2009;14,669-674
Kristina, et al Journal of Global Pharma Technology 2020; 12(6), 560-566
 INDONESIAN
Etiology of Stage 5 CKD Patients in Indonesia
RENAL REGISTRY
Jumlah Pasien Penyakit Ginjal Kronik Tahap 5/CKD Stage 5 (N18.1)
berdasarkan Diagnosa Etiologi Di Indonesia
E1 (Glumerulopati Primer) (GNC)
E10 (Tidak Diketahui) 8%
16%

Hypertension and
E9 (Lain-Lain)
Diabetes was found to be 4%
the most common E8 (Pielonefritis
etiologies found in Chronic0 (PNC)
2%
Patients with CKD St.5 E2 (Nefropati Diabetika)
E7 (Nefropati Obstruksi)
3% 29%
E6 (Nefropati Asam Urat)
1%

E5 (Ginjal Polikistik)
1%
E3 (Nefropati Lupus)
E4 (Penyakit ginjal Hipertensi) (SLE)
CKD : Chronic Kidney Disease 35% 1%
Indonesian Renal Registry 2020
 Kesintasan Kumulatif
Survival Function Pasien PGK on HD reguler
Survival Function
1.0
0

• Insiden luaran kematian dalam waktu 3

0.8

tahun mencapai 47,36% (all-cause

Cum Survival

0.6
mortality)15,78%/tahun.

0.4 • Waktu kesintasan (survival) kumulatif pada

keseluruhan subyek: 27,0131,24 bulan.
0.2

0.0

0 10 20 30 40
1. Mahadita GW, Kandarini Y, Widiana IGR. Kidney Int Reports 2022; 7: S114–S115.
Survival Time (bulan)
 Renal Outcome Trials Have Historically
Focused on Patients With T2D
9000 Nondiabetes population T2D population

8000
5000

4000
Population

3000

2000

1000

0
Series1

C z in

-D l

96 ne
N an
D n

T) 8 a
(R Olm R) 6 n
06 il

N l

D n
O yl

A an AL an

(A or T) 10 il
PE il
96 il

N ri
A n
-1 20

R e
EI ri

EA lf
20 epr

U re

N ta

EN nta

D am
O ipr
19 epr

E) 7

)5

C id
M rta

) 11
O op
T) 5
E) 5

C eth
)3

(A A ) 4

Irb ) 5

)5
EP ± l ) 5
(R mip

)9
)2

19 pi
P) 5
)1

(ID art

Li (BE ve ) 5
R a

A t
EN flo
IC T-1

O en
IT ki

N ar

A ex
N
ar O-H am

h di
(T tin

H isin
/2

A sa

no NE rap
ou az

SC se
io az

LT lis

EA m

es
ED li

Lo (RE Los
A
(S as
PP S

do -M d

rd i f e
IC
R ag
O e
(H en

(A o
ch n

R R

o
(E A

(B ne
tr

po

Av
e

an Sun Sul

ga n
(C an
D

R
B
as B

lo
be

±
C

xo

il
ar

il
(V art

pr
IC

do

pr
N
D

la
(M

(M

(
B

si
Tr
CKD = chronic kidney disease; T2D = type 2 diabetes.
1. Schulman G et al. J Am Soc Nephrol. 2015;26:1732–1746; 2. Maschio G et al. N Engl J Med. 1996;334:939–945; 3. Hou FF et al. N Engl J Med. 2006;354:131–140; 4. GISEN Group. Lancet 1997;349:1857–
1863; 5. Chan GC et al. Nephrol Dial Transplant. 2016;31:359–368; 6. Heerspink HJL et al. Lancet. 2019;393:1937-1947; 7. Perkovic V et al. N Engl J Med. 2019;380:2295–2306;
8. Pfeffer MA et al N Engl J Med. 2009;361:2019–2032; 9. HOPE Study Investigators. Lancet. 2000;355:253–259; 10. Ruggenenti P et al. N Engl J Med. 2004;351:1941–1951; 11. Agardh CD et al. J Hum
Hypertens. 1996;10:185–192.
Therapeutic Innovation to Prevent New Onset or
Worsening Renal Function Has Been Limited
Drug/Class Study Name Patient Population Year Effect on CKD
progression

ACEi
Ramipril REIN2 Non-DM Nephropathy 1997
(eGFR 20-70 mL/min/1.73 m2 ; UPE >1g/24h)

ARBs
Irbesartan IDNT3 T2D; CKD (UPE ≥900mg/24h; SCr 1-3 mg/dL) 2001
Losartan RENAAL4 T2D; CKD (UACR ≥300; SCr 1.3-3 mg/dL) 2001
Olmesartan ROADMAP5 T2D; normoalbuminuria 2011

ACEi/ARB Combo
Telmisartan/ramipril ONTARGET6 ASCVD or diabetes with end-organ damage 2008
Losartan/lisinopril VA NEPHRON-D7 T2D; CKD (eGFR ≥30 to <90mL/min/1.73 m2; UACR ≥300) 2013

DRI
Aliskiren ALTITUDE8 T2D; CKD (eGFR ≥30 and <60mL/min/1.73 m2) or CVD 2012

Glycosaminoglycan
Sulodexide Sun MACRO9,10 T2D; CKD (UPE >900mg/24h) 2012

Anti-inflammatory
Bardoxolone methyl BEACON11 T2D; CKD (eGFR 15 to <30 mL/min/1.73 m2) 2013

1. Chan GC, Tang SC. Diabetic nephropathy: landmark clinical trials and tribulations. Nephrol Dial Transplant. 2016;31:359-368.
Mortality and CV risks are elevated,
regardless of CKD etiology
Hypertensive IgA Diabetic
nephropathy nephropathy
nephropathy

>3× 53% ~6×

Greater risk of Greater risk
Increased
CV events of CV events
mortality risk2,b
and mortality1,a and mortality1,a

70% of patients received 74% of patients received an 76% of patients received an

an ACE inhibitor/ARB ACE inhibitor/ARB ACE inhibitor/ARB

a
Compared with primary renal disease defined by primary glomerulonephritis and tubulointerstitial nephritis; bData compared with the general population.
1. Nakayama M et al. Hypertens Res. 2011;34(10):1106-1110; 2. Jarrick S et al. Article and online supplemental material. J Am Soc Nephrol. 2019;30(5):866-876.
The risk of mortality and ESKD increases as CKD progresses,
regardless of diabetes status

Decreasing eGFR Increasing UACR

leads to… leads to…

⇧ MORTALITY RISK WITH

T2D WITHOUT ⇧ MORTALITY RISK
⇧ ESKD RISK
T2D ⇧ ESKD RISK
CKD Burden
SGLT2 inhibitor in CKD
From Prevention to Treatment
 SGLT2 Inhibition has a Number of Potential Direct and
Downstream Effects which may Result in Beneficial Effects on
Kidney Function1
2 As CKD progresses elevated intraglomerular pressure is a
Increased common feature and driver of several CKD etiologies2,3
sodium delivery
to macula
densa1 Tubuloglomerular feedback restoration with SGLT2i:
3 • Inhibits proximal glucose reabsorption1
TGF leads
to • Blocks proximal sodium reabsorption1
↓ intraglomerular
pressure and • Leads to increased distal delivery of sodium to the macula
↓ proteinuria1 densa1
• TGF restoration resulting in decreased glomerular
1 hyperfiltration and hydrostatic pressure1,4,5
Blocks proximal
glucose and
sodium Additional downstream effects:1
reabsorption1
• Decreased urinary albumin excretion may reduce pro-
inflammatory pathway activation and direct tubular toxicity
• Improved cardiac function and increased hematocrit
concentration may result in increased oxygen delivery to the
kidney and improvements in renal hypoxia
Na = sodium; SGLT2 = sodium–glucose co-transporter 2; TGF = tubuloglomerular feedback.
1. Heerspink HJL et al. Kidney Int. 2018;94:26-39; 2. Helal I et al. Nat Rev Nephrol. 2012;8:293-300; 3. Palatini P. Nephrol Dial Transplant. 2012;27:1708-1714. 4. Schefold JC et al. Nat Rev 16
Nephrol. 2016;12:610-623; 5. Zelniker TA et al. J Am Coll Cardiol. 2018;72:1845-1855.
Key Physiological Effects of SGLT-2 Inhibition
↑NATRIURESIS
↑GLYCOSURIA ↑OSMOTIC DIURESIS

↓Plasma volume
↓HbA1c ↓Interstitial fluid

Glycemic Extra-
Glycemic
↓Glucotoxicity Effects of
Effects of
SGLT-2i
↓Insulin resistance ↓Blood pressure
↑β-cell function SGLT-2i

↓Glomerular
↓Body weight hyperfiltration

Metabolic, Cardiovascular, and

Renal Improvements

HbA1C=hemoglobin A1C; SGLT-2=sodium-glucose co-transporter 2; SGLT-2i=sodium-glucose co-transporter 2 inhibitor.

1. Heerspink HJL, et al. Kidney Int. 2018;94(1):26-39. 2. van Baar MJB, et al. Diabetes Care. 2018;41(8):1543-1556. 3. Tamargo J. Eur Cardiol. 2019;14(1):23-32.
Potential Effects By Which SGLT-2 Inhibition
Improves Renal Outcome
SGLT-2 INHIBITION CLINICAL EFFECTS

Reduce Glomerular Pressure1

↑Afferent vasoconstriction Stabilization of eGFR2
↓Glomerular hyperfiltration

Neurohormonal Improvement Protection Against

↓Intrarenal RAAS activity3 ↓Blood Pressure1 Diabetic
↓SNS activity4
Nephropathy1,2

Inflammation/Fibrosis
Reductions1,2 ↓Tubular/Glomerular Injury1,2
↓Inflammatory markers ↓Albuminuria
↓Fibrotic markers

Decreased Renal Workload

and Hypoxia1,2 ↓Renal Ischemic Injury1
↓Solute transport ↑Hb/hematocrit2
↓Oxygen demand

eGFR=estimated glomerular filtration rate; Hb=hemoglobin; RAAS=renin angiotensin aldosterone system; SNS=sympathetic nervous system. Preserved
1. Heerspink HJL, et al. Kidney Int. 2018;94(1):26-39. 2. Tamargo J. Eur Cardiol. 2019;14(1):23-32. 3. Shin SJ, et al. PLoS One. 2016;11:e0165703. 4.
Sano M. J Cardiol. 2018;71(5):471-476.
Renal Function2
CKD Burden
SGLT2 inhibitor in CKD
From Prevention to Treatment
 SGLT2i Renal Outcome Trials
DAPA-CKD1,2 CREDENCE3 EMPA-KIDNEY4-6
N = 4304 N = 4401 N = 6609

Status Completed Completed Stopped Early

Intervention Dapagliflozin vs Placebo Canagliflozin vs Placebo Empagliflozin vs Placebo

≥4 weeks stable on ACEi or ARB ≥4 weeks stable on ACEi or ARB ≥8-12 weeks on ACEi or ARB

• T2D and non-DM • T2D • T2D and non-DM

• eGFR ≥25 to ≤75 mL/min/1.73m2 • eGFR ≥30 to <90 mL/min/1.73m2 • eGFR ≥20 to <45 mL/min/1.73m2
Patient Population or ≥45 to <90 mL/min/1.73m2 and UACR
• UACR ≥200 to ≤5000 mg/g • UACR >300 to ≤5000 mg/g
≥200 mg/g

Composite Composite Composite

• ≥50% sustained eGFR decline • Doubling of serum creatinine • Kidney disease progression
Primary Endpoint • ESKD • ESKD • CV death
• Renal or CV death • Renal or CV death

• Renal composite • CV death or hHF • CV death or hHF

• CV death or hHF • CV death, MI, or stroke • All-cause hospitalizations
• All-cause death • hHF • All-cause death
Secondary • Renal composite
Endpoints • Kidney disease progression
• CV death • CV death
• All-cause death
•
• CV death or ESKD
Composite of CV death, MI, stroke, hHF or
hospitalization for UA

Disclaimer : in Indonesia, Dapagliflozin is currently approved for

treatment of CKD for eGFR 30-75 ml/min/1.73
1. Study NCT03036150. ClinicalTrials.gov website; 2. Heerspink HJL et al. Nephrol Dial Transplant. 2020;35:274–282; 3. Perkovic V et al. N Engl J Med. 2019;380:2295-2306; 4. Study NCT03594110. ClinicalTrials.gov website; 5. Boehringer Ingelheim press release.
Published March 16, 2022; 6. EMPA-KIDNEY Collaborative Group. Online ahead of print. Nephrol Dial Transplant. 2022; 7. Study NCT02540993. ClinicalTrials.gov website; 8. Bakris GL et al. Am J Nephrol. 2019;50:333-344.
 DAPA-CKD Was a Landmark Trial Assessing Dapagliflozin
in Over 4,000 Patients With CKD, With and Without T2D 1,2
To assess whether treatment with dapagliflozin, compared with placebo, reduced the risk of renal and CV events in patients with
Objective
CKD with or without T2D, and who were receiving standard of care including a stable dose of an ACEi or ARB

Key Inclusion Criteria

• ≥18 years of age Primary Outcome
• eGFR ≥25 to ≤75 mL/min/1.73m2
• UACR ≥200 to ≤5000 mg/g Composite of sustained ≥50% eGFR decline,
Dapagliflozin 10 mg ESKDa, renal or CV death

Double-blind
• Stable dose of ACEi/ARB for

End Points
+ standard of care
≥4 weeks
• With and without T2D 1:1 Secondary Outcomes
Key Exclusion Criteria Placebo • Composite of sustained
• T1D + standard of care ≥50% eGFR decline, ESKD, or renal death
• Polycystic kidney disease, • Composite of CV death or hHF
lupus nephritis, ANCA-
associated vasculitis • All-cause mortality
4304 Randomized
• Immunosuppressive therapy
Median follow-up 2.4 years
≤6 months prior to enrollment
Disclaimer : in Indonesia, Dapagliflozin is currently approved for treatment of CKD for eGFR
30-75 ml/min/1.73
ESKD defined as the need for maintenance dialysis (peritoneal or hemodialysis) for more than 28 days, renal transplantation or sustained eGFR <15mL/min/1.73m2 for at least 28 days.
a

ACEi = angiotensin-converting enzyme inhibitor; ANCA = anti-neutrophil cytoplasmic antibody; ARB = angiotensin-receptor blocker; CKD = chronic kidney disease; CV = cardiovascular; eGFR = estimated
glomerular filtration rate; ESKD = end-stage kidney disease; hHF = hospitalization for heart failure; T1D = type 1 diabetes; T2D = type 2 diabetes; UACR = urinary albumin-to-creatinine ratio.
1. Heerspink HJL et al. Nephrol Dial Transplant. 2020;35:274–282; 2. Heerspink HJL et al. N Engl J Med. 2020; 383:1436-1446.
DAPA-CKD
Demographic and Baseline Characteristics Were Well-
Balanced Between Treatment Groups
Dapagliflozin 10 mg Placebo
(N=2152) (N=2152)
Age, years, mean 61.8 61.9
Gender, female, % 32.9 33.3
Racea, %
White 52.2 54.2
Black or African-American 4.8 4.0
Asian 34.8 33.4
Other 8.1 8.4

Weight, kg 81.5 82.0

Body mass index, kg/m2 29.4 29.6
Current smoker, % 13.2 14.0
Blood pressure, mmHg, mean
Systolic blood pressure 136.7 137.4
Diastolic blood pressure 77.5 77.5
Hemoglobin, g/L 128.6 127.9
Serum potassium, mEq/L 4.6 4.6
a
Race was reported by the investigators; the designation ‘other’ includes Native Hawaiian or other Pacific
Disclaimer Dapagliflozin is currently approved for treatment of CKD for eGFR 30-75 Islander; American Indian or Alaska Native and Other.
ml/min/1.73 BL = baseline.
Heerspink HJL et al. N Engl J Med. 2020; 383:1436-1446.
DAPA-CKD
Medical History and Baseline Medications Were Well-Balanced
Between Treatment Groups
Dapagliflozin 10 mg Placebo
(N=2152) (N=2152)

Type 2 diabetes, % 67.6 67.4

CV disease, % 37.8 37.0

Heart failure, % 10.9 10.8

Prior medication, %

ACEi 31.3 31.6

ARB 67.1 66.3

Diuretic 43.1 44.3

Statin 64.8 65.0

ACEi = angiotensin-converting enzyme inhibitor; ARB = angiotensin-receptor blocker; BL = baseline; CKD = chronic
kidney disease; CV = cardiovascular
Disclaimer : in Indonesia, Dapagliflozin is currently approved for treatment of CKD for eGFR 30-75
Heerspink HJL et al. N Engl J Med. 2020; 383:1436-1446.
ml/min/1.73
DAPA-CKD

Diabetes Status and Investigator-reported Cause of Kidney

Disease at Baseline
Investigator-reported Cause
Diabetes Status of Kidney Disease

9.6%

16.0%
32.5%
58.3%
58.3%
67.5% 16.1%

With type 2 diabetes Without type 2 diabetes Diabetic nephropathy Glomerulonephritides

Ischemic / hypertensive nephropathy Other / unknown causes

Wheeler DC et al. Nephrol Dial Transplant. 2020;35:1700–1711. CKD Etiologies

 DAPA-CKD

Dapagliflozin Significantly Slowed Progression of Kidney Disease and Reduced the

Risk of Adverse Outcomes (Sustained ≥ 50% eGFR Decline, ESKD, Renal or CV
Death)a,1
24
DAPA Placebo HR (95% CI) p-value2 Placebo
9.2% 14.5% 0.61 (0.51-0.72) 0.000000028 312 events
20
39%​
RRR
Cumulative Incidence %

16

5.3% ARR
12 NNT=19b
DAPA 10 mg
8 197 events

Disclaimer : in Indonesia,
0
Dapagliflozin is currently
0 4 8 12 16 20 24 28 32 approved for treatment of
N at Risk Months from Randomization CKD for eGFR 30-75
DAPA 10 mg 2152 2001 1955 1898 1841 1701 1288 831 309 ml/min/1.73
Placebo 2152 1993 1936 1858 1791 1664 1232 774 270

ESKD defined as the need for maintenance dialysis (peritoneal or hemodialysis) for at least 28 days and renal transplantation or sustained eGFR <15mL/min/1.73m 2 for at least 28 days. Renal death was defined as death due to ESKD when dialysis treatment was
deliberately withheld for any reason.3; b95% CI, 15 to 27.
ARR = absolute risk reduction; CV = cardiovascular; DAPA = dapagliflozin; eGFR = estimated glomerular filtration rate; ESKD = end-stage kidney disease; HR = hazard ratio; ; NNT = number needed to treat; RRR = relative risk reduction.
1. Heerspink HJL et al. N Engl J Med. 2020; 383:1436-1446; 2. Heerspink HJL. Presented at: ESC Congress – The Digital Experience; August 29 – September 1, 2020; 3. Heerspink HJL et al. Nephrol Dial Transplant. 2020;35:274–282.
 Subgroup – T2D Status

Primary Outcome (Sustained ≥50% eGFR Decline, ESKD, Renal or CV

Deatha) by Diabetes Status
Patients With T2D Patients Without T2D

24 Hazard Ratio, 0.64 (95% CI, 0.52-0.79) 24 Hazard Ratio, 0.50 (95% CI, 0.35-0.72)

20 20
Placebo
Cumulative Incidence (%)

Cumulative Incidence (%)

Placebo
16 16

12 12

Dapagliflozin
8 8

Dapagliflozin
4 4

0 0
0 4 8 12 16 20 24 28 32 0 4 8 12 16 20 24 28 32
No at Risk Months Since Randomization No at Risk Months Since Randomization
Dapagliflozin 1455 1383 1349 1307 1262 1155 910 580 215 Dapagliflozin 697 618 606 591 579 546 378 251 94
Placebo 1451 1360 1321 1275 1224 1130 868 545 190 Placebo 701 633 615 583 567 534 364 229 80

a
ESKD defined as the need for maintenance dialysis (peritoneal or hemodialysis) for at least 28 days and renal
transplantation or sustained eGFR <15mL/min/1.73m2 for at least 28 days. Renal death was defined as death due to ESKD
p-interaction=0.24 when dialysis treatment was deliberately withheld for any reason.2
CV= cardiovascular; ESKD = end-stage kidney disease; eGFR = estimated glomerular filtration rate; T2D = type 2 diabetes.
Disclaimer : in Indonesia, Dapagliflozin is currently approved for treatment of CKD for 1. Wheeler DC et al. Lancet Diabetes Endocrinol. 2021;9:22–31; 2. Heerspink HJL et al. Nephrol Dial Transplant.
2020;35:274–282.
eGFR 30-75 ml/min/1.73
 DAPA-CKD

Treatment Benefit Was Consistent Across Key Pre-Specified

Subgroups1-3

Number of Events

DAPA 10 mg Placebo p-value

HR (95% CI) (N=2152) (N=2152) HR 95% CI Interaction2
Composite of ≥50% eGFR Decline, ESKD, or Renal or CV Death
All Patients 197 312 0.61 (0.51, 0.72)
T2D at Baseline 0.24
Yes 152 229 0.64 (0.52, 0.79)
No 45 83 0.50 (0.35, 0.72)
UACR (mg/g) at Baseline 0.52
≤1000 44 84 0.54 (0.37, 0.77)
>1000 153 228 0.62 (0.50, 0.76)
eGFR (mL/min/1.73m2) at Baseline 0.22
<45 152 217 0.63 (0.51, 0.78)
≥45 45 95 0.49 (0.34, 0.69)
CKD Stage at Baseline3,a 0.22
Stage 4 59 87 0.73 (0.53, 1.02)
Stage 2/3 138 225 0.58 (0.47, 0.71)

0.25 0.5 1.0 2.0

DAPA 10 mg Better Placebo Better a
Stage 4 CKD = eGFR <30 mL/min/1.73m2; Stage 2/3 CKD = eGFR ≥30 mL/min/1.73m2.
CV = cardiovascular; CKD = chronic kidney disease; DAPA = dapagliflozin; eGFR = estimated glomerular filtration rate;
ESKD = end-stage kidney disease; T2D = type 2 diabetes; UACR = urinary albumin-to-creatinine ratio.
Disclaimer : in Indonesia, Dapagliflozin is currently approved for treatment of CKD for 1. Heerspink HJL et al. N Engl J Med. 2020; 383:1436-1446; 2. Heerspink HJL. Presented at: ESC Congress – The Digital
Experience; August 29 – September 1, 2020; 3. Chertow GM et al. Presented at: WCN; April 16-19, 2021; Virtual.
eGFR 30-75 ml/min/1.73
 Subgroup – T2D Status

Safety Outcomes1
With T2D Without T2D

Dapagliflozin 10 Dapagliflozin 10
Placebo Odds Ratio (95% Placebo Odds Ratio (95%
mg mg p-interaction
(n=1450) CI) (n=699) CI)
Safety outcomes , %
a (n=1453) (n=696)

Discontinuation due to AE 6 6 0.86 (0.63, 1.17) 5 4 1.26 (0.77, 2.09) 0.20

Any serious AEb 33 39 0.79 (0.68, 0.92) 22 24 0.88 (0.68, 1.12) 0.48

AE of special interest

Amputationc 2 3 0.92 (0.57, 1.46) 0 <1% NA 0.26

Any definite or probable DKA 0 <1% NA - - - NA

Fractured 4 4 1.28 (0.89, 1.87) 3 3 1.12 (0.59, 2.15) 0.72

Renal-related adverse eventd 8 10 0.80 (0.62, 1.03) 5 6 0.85 (0.53, 1.35) 0.83

Major hypoglycemiae 1 2 0.49 (0.25, 0.93) - - - 1.00

Volume depletiond 6 5 1.31 (0.96, 1.81) 5 3 1.90 (1.09, 3.41) 0.27

Disclaimer : in Indonesia, Dapagliflozin is currently approved for treatment of CKD for eGFR 30-75 ml/min/1.73

Disclaimer: In Indonesia, dapagliflozin is currently not indicated for treatment of CKD

a
Safety analysis set; bIncludes death; cSurgical or spontaneous/non-surgical amputation, excluding amputation due to trauma; dBased on pre-defined list of preferred terms; eAE with the following criteria confirmed by the investigator: i) symptoms of severe impairment in consciousness or behavior,
ii) need of external assistance, iii) intervention to treat hypoglycemia, iv) prompt recovery of acute symptoms following the intervention.
29 AE = adverse event; DKA = diabetic ketoacidosis; NA = not applicable; T2D = type 2 diabetes.
Wheeler DC et al. Lancet Diabetes Endocrinol. 2021;9:22–31.
Dapagliflozin Addresses the Burden of CKD Across the Disease Spectrum in T2D to
Prevent Onset, Slow Progression and Improve Outcomes of Patients

Dapagliflozin has demonstrated significant Dapagliflozin significantly reduced the risk of

reductions in the risk of new or worsening kidney disease progression, ESKD and risk
nephropathy in patients with T2D and of death in patients with CKD with and
predominantly preserved renal function1–3 without T2D4

PREVENTION TREATMENT
Patient population
Risk of HF / CV
17,160 N 4304
100 Patients with T2D (%) 68 events / Mortality
13 Median UACR (mg/g) 949
85 Mean eGFR (mL/min/1.73m2) 43

Outcomes
47% RRR (HR, 0.53 [95% CI, 0.43-0.66])
a
Renal progression 44% RRRb (HR, 0.56 [95% CI, 0.45-0.68])
17% RRR (HR, 0.83 [95% CI, 0.73-0.95]) CV death or hHF 29% RRR (HR, 0.71 [95% CI, 0.55-0.92])
NS (HR, 0.93 [95% CI, 0.82-1.04]) All-cause mortality 31% RRR (HR, 0.69 [95% CI, 0.53-0.88])

Dapagliflozin Placebo Safety Dapagliflozin Placebo

34.1% 36.2% Any SAE 29.5% 33.9%
8.1% 6.9% AEs that led to discontinuation 5.5% 5.7%
1.4% 1.3% Amputation 1.6% 1.8%
0.3% 0.1% Diabetic ketoacidosis 0.0% 0.1%
5.3% 5.1% Fracture 4.0% 3.2%
0.7% 1% Major hypoglycemic event 0.7% 1.3%
2.5% 2.4% Symptoms of volume depletion 5.9% 4.2%
Disclaimer: In Indonesia, dapagliflozin is currently not indicated for treatment of CKD Disclaimer : in Indonesia, Dapagliflozin is currently approved for treatment of
See slide notes for footnotes, abbreviations, and references.
CKD for eGFR 30-75 ml/min/1.73
Conclusion: Dapagliflozin reduced kidney and cardiovascular
events and prolonged survival in patients with CKD, with
and without type 2 diabetes, with no apparent effect
modification by geographic region.

Kidney International Reports (2022) 7, 699–707

 There is a need to diagnose early and intervene early with Dapagliflozin
to slow the growing burden of CKD and transform patient outcomes

1 CKD is a major public health crisis, with increasing costs, mortality, and KRT
prevalence adding to the global burden1,2

2 The risks of mortality and CV events are elevated, regardless of CKD

etiology3,4

3
Dapagliflozin is the first therapy in over 20 years to reduce the risk of CKD
progression, CV events, and mortality in patients with CKD, across a broad
range of etiologies5-7

1. Jager KJ et al. Kidney Int. 2019;96(5):1048-1050; 2. Mennini FS et al. Poster presented at: ISPOR Europe (Virtual Meeting); November 30-December 3, 2021; 3. Jarrick S
et al. J Am Soc Nephrol. 2019;30(5):866-876; 4. Nakayama M et al. Hypertens Res. 2011;34(10):1106-1110; 5. Heerspink HJL et al. N Engl J Med. 2020;383(15):1436-1446;
6. Wheeler DC et al. Lancet Diabetes Endocrinol. 2021;9(1):22-31; 7. Garcia Sanchez JJ et al. Adv Ther. 2022;39(1):193-220. 32
THANK YOU