Dr. George L. Bakris, MD, prepared T2DM infographics for this CME activity titled "Show Me the Data: Improving Renal Outcomes With Glucose-Lowering Therapy in the Individualized Management of T2DM." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at https://bit.ly/32r5mw6. CME credit will be available until November 1, 2021.

1. Diabetes
Hyperten
sion
Cyst
ickidn
ey
Glome
rulonephritis
Visualizing the Relationship Between T2DM and CKD
Global Trends in T2DM:
Estimated Increase in Patients Aged 20-79 Years (2017-2045)7
48% increase
2017
Diabetes Is the Major Cause of Kidney Disease
in the United States1-6
T2DM, CVD, and CKD Are Interrelated
T2DM ASCVD
HF CKD
425
million
629
million
North America
and Caribbean
35% increase
South and
Central America
62% increase
Middle East and North Africa
110% increase
Africa
156% increase
Southeast Asia
84% increase
Western Pacific
15% increase
Europe
16% increase
2045
Worldwide
Progression of Diabetic Kidney Disease8
P
athophysiology
of
Diabe
tic Kidney Dis
ease
Hemodynamic and metabolic effects
Hyper-reabsorption stress Hypertrophy Atrophy
Loss of glycocalyx Loss of fenestration Microvascular rarefication
Hyperfiltration stress
Tubules
Endothelial Cells
Podocytes Podocyte hypertrophy Podocyte loss
Inflammation and/or scarring
Tubulointerstitial fibrosis
Glomerulosclerosis
Cellular and tissue remodeling
Show Me the Data: Improving Renal Outcomes With Glucose-Lowering Therapy
in the Individualized Management of T2DM
Full references, accreditation, and disclosure information available at www.PeerView.com/RBT930

2. Exploring the Science: Improving Renal Outcomes in Patients With T2DM
Multidimensional Effects at GFR >60 mL/min/1.73 m2
14-15
Outcome Trials With SGLT2 Inhibitors16-28
ADA Standards
of Medical Care
in Diabetes9
FDA-Approved
SGLT2 Inhibitors10-13
Cardiovascular
CKD Staging
Albuminuria Stages, Range (mg/g), and Description
A1: <30
Normoalbuminuria
≥90
(Stage 1)
60-90
(Stage 2)
45-59
(Stage 3a)
GFRCategories,mL/min/1.73m2
30-44
(Stage 3b)
15-29
(Stage 4)
<15
(ESKD 6)
A2: 30-300
Microalbuminuria
A3: >300
Macroalbuminuria
Renal
CANVAS CREDENCE
DECLARE-TIMI 58 DAPA-CKD
EMPA-REG OUTCOME EMPA-KIDNEY
VERTIS CV
VERTIS MET
and SU
Canagliflozin
Dapagliflozin
Empagliflozin
Ertugliflozin
SGLT2 inhibition
Cardiac and renal protection
Negative
caloric balance
↓ A1C ↑ Uricosuria
↓ Blood
pressure
↓ Plasma
volume
↑ Tubuloglo-
merular
feedback
↓ Total body
fat mass
↓ Inflammation
↓ Glucose toxicity
↓ Plasma
uric acid
↓ Arterial
stiffness
↓ Myocardial
stretch
Afferent
arteriole
constriction
Glycosuria Natriuresis
C
D
E
V
C
D
E
V
eGFR ≥30-<90 mL/min/1.73 m2
and UACR ≥300 mg/g
eGFR ≥25-<75 mL/min/1.73 m2
and UACR ≥200 mg/g
eGFR ≥45-<75 mL/min/1.73 m2
and UACR ≥200 mg/g
or eGFR ≥20-<45 mL/min/1.73 m2
Post-hoc analysis; mean (SD) BL eGFR
88.2 mL/min/1.73 m2
and BL UACR 1.31 mg/mmol
↓ Epicardial fat ↓ Atherosclerosis
↓ Ventricular
arrhythmias
Activation of
ACE2-Ang1/7
↓ Inflammation
↓ Fibrosis
↑ Cardiac
contractility
↓ Intraglomerular
hypertension
↓ Hyperfiltration
Show Me the Data: Improving Renal Outcomes With Glucose-Lowering Therapy
in the Individualized Management of T2DM
Full references, accreditation, and disclosure information available at www.PeerView.com/RBT930

3. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. Brenner B et al. N Engl J Med. 2001;345:861-869. 2. Lewis EJ et al. N Eng J Med. 2001;345:851-860. 3. Zelniker TA et al. Circulation. 2019;139:2022-2031.
50
40
30
20
10
0
0.6
0.5
0.4
0.3
0.2
0.1
0
0 12 24 36 48
Placebo
Losartan
RESIDUAL RISK
RENAAL
Risk reduction: 16%
P = .02
Time of Study, mo Follow-Up, mo
PrimaryCompositeEndpoint,%
Risk reduction: 20%
P = .02
Irbesartan
Amlodipine
Placebo
PrimaryCompositeEndpoint,%
IDNT
0 6 12 18 24 30 36 42 48 54
RESIDUAL RISK
Doubling of Serum Creatinine, ESKD, or Death1,2
SGLT2i CVOTs: Meta-Analysis3
a
Meta-analysis of three CVOTs with a total of 34,322 participants (EMPA-REG OUTCOME, CANVAS, DECLARE).
0
-10
-20
-30
-40
-50
RelativeRisk
Reduction,%a
HR
(95% CI)
P
0.89
(0.83-0.96)
.001
0.84
(0.75-0.94)
.002
0.89
(0.80-0.98)
.018
0.97
(0.86-1.10)
NS
0.69
(0.61-0.79)
<.001
0.62
(0.58-0.67)
<.001
0.55
(0.48-0.64)
<.001
-11%
-16%
-11%
-3%
-31%
-38%
-45%
MACE
CV
Death
Fatal or
Nonfatal MI
Fatal or
Nonfatal
Stroke HHF
Pure Renal
Endpoints
Worsening
of Kidney
Function

4. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. Jardine MJ et al. Am J Nephrol. 2017;46:462-472. 2. Perkovic V et al. N Engl J Med. 2019;380:2295-2306. 3. Invokana (canagliflozin) Prescribing Information. http://www.janssenlabels.com/package-
insert/product-monograph/prescribing-information/INVOKANA-pi.pdf. 4. Jardine MJ et al. J Am Soc Nephrol. 2020;31:1128-1139.
CREDENCE Study Design
The CREDENCE Study1-4
Inclusion Criteria
ü ≥30 years
ü A1C ≥6.5% and
≤12.0%
ü eGFR ≥30 and
<90 mL/min/1.73 m2
ü UACR >300 and
≤5,000 mg/g
• Canagliflozin
100 mg
• Placebo
• 1:1 randomization,
double-blind
• 2.62 years (median)
• Event-driven
(405 events)
• Composite renal
endpoint
• ESKD
• Doubling of sCr
• Renal death
• CV death
û Dialysis
û Kidney transplant
û Recent CV event
û NYHA class IV
û HF
Exclusion Criteria Interventions Follow-Up Primary Outcome
Population:
• Multicenter (34 countries); target N = 4,401
• Patients with T2DM and albuminuria using ACEi or ARB
-20
-18
-16
-14
-12
-10
-8
-6
-4
-2
0
Least-SquareMeanChange,
mL/min/1.73m2
Time Since Randomization, mo
0
200
400
600
800
1,000
1,200
0 6 12 18 24 30 36 '"
GeometricMean
Time Since Randomization, mo
UACR
Median Baseline
Canagliflozin 913.5
Placebo 918.0
Baseline, mL/min/1.73 m2
Canagliflozin 56.4
Placebo 56.0
Placebo
Canagliflozin
Canagliflozin
Placebo
No. of Patients
Placebo 2,113 2,061 1,986 1,865 1,714 1,158 685 251
Canagliflozin 2,114 2,070 2,019 1,917 1,819 1,245 730 271
0 6 12 18 24 30 36 42
No. of Patients
Placebo 2,178 1,985 1,882 1,720 1,536 1,006 583 210
Canagliflozin 2,179 2,005 1,919 1,782 1,648 1,116 652 241
Change From Baseline in eGFR
32%
reduction

5. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. Jardine MJ et al. Am J Nephrol. 2017;46:462-472. 2. Perkovic V et al. N Engl J Med. 2019;380:2295-2306. 3. Invokana (canagliflozin) Prescribing Information. http://www.janssenlabels.com/package-
insert/product-monograph/prescribing-information/INVOKANA-pi.pdf. 4. Jardine MJ et al. J Am Soc Nephrol. 2020;31:1128-1139.
The CREDENCE Study1-4
Renal-Specific Composite Outcome of ESKD,
Doubling of Creatinine, or Renal Deatha
a
Indicated to reduce the risk of ESKD, doubling of serum creatinine, CV death, and hospitalization for HF in adults with T2DM and
diabetic nephropathy with albuminuria.
PatientsWithanEvent,%
Time Since Randomization, mo
0
5
10
15
20
0 6 12 18 24 30 36 42
HR = 0.66 (95% Cl, 0.53-0.81)
P < .001
Placebo
Canagliflozin
No. at Risk
Placebo 2,199 2,178 2,131 2,046 1,724 1,129 621 170
Canagliflozin 2,202 2,181 2,144 2,080 1,786 1,211 646 196
34% risk
reduction
Effects of Canagliflozin on eGFR Slope by Screening eGFR
0
10
20
30
40
50
60
70
80
90
0 6 12 18 24 30 36 42
AdjustedMean(SE)eGFR,
mL/min/1.73m2
Time Since Randomization, mo
Screening eGFR 60-<90 mL/min/1.73 m2
Screening eGFR 45-<60 mL/min/1.73 m2
Canagliflozin
Placebo
Screening eGFR 30-<45 mL/min/1.73 m2

6. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. Jardine MJ et al. J Am Soc Nephrol. 2020;31:1128-1139. 2. Invokana (canagliflozin) Prescribing Information. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-
information/INVOKANA-pi.pdf.
CREDENCE: AEs Stratified by Degree of Renal Impairment1
FDA Label Update: Canagliflozin2
a
Based on confirmed and adjudicated results.
Screening eGFR,
mL/min/1.73 m2 HR (95% CI) P
HHF
All
30-<45
45-<60
60-<90
0.61 (0.47-0.80)
0.70 (0.46-1.06)
0.43 (0.26-0.72)
0.72 (0.44-1.16)
.27
All SAEs
All
30-<45
45-<60
60-<90
0.87 (0.79-0.97)
0.85 (0.71-1.00)
0.78 (0.65-0.93)
0.99 (0.84-1.17)
.15
Fracturea
All
30-<45
45-<60
60-<90
0.98 (0.70-1.37)
1.04 (0.58-1.86)
0.82 (0.44-1.50)
1.08 (0.61-1.91)
.77
Amputation
All
30-<45
45-<60
60-<90
1.11 (0.79-1.56)
1.36 (0.73-2.54)
0.64 (0.33-1.22)
1.40 (0.82-2.39)
.14
Favors canagliflozin Favors placebo
0.25 0.5 1.0 2.0 4.0
1. Indications and usage updated
• Adults with T2DM and
eGFR ≥30 mL/min/1.73 m2
, with or
without albuminuria, may start
canagliflozin 100 mg
Continuation of canagliflozin is
not recommended in patients
with eGFR <30 mL/min/1.73 m2
unless albuminuria is >300 mg/d
2. Boxed warnings removed
• Lower extremity amputations
3. Warnings and precautions removed
• AKI as a stand-alone warning
• Warning that symptomatic hypotension
can occur in patients on ACEi/ARBs
FDA Label Update: Canagliflozin

7. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. Invokana (canagliflozin) Prescribing Information. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/INVOKANA-pi.pdf. 2. Farxiga (dapagliflozin)
Prescribing Information. https://www.azpicentral.com/farxiga/farxiga.pdf#page=1. 3. Jardiance (empagliflozin) Prescribing Information. https://docs.boehringer-ingelheim.com/Prescribing%20
Information/PIs/Jardiance/jardiance.pdf. 4. Steglatro (ertugliflozin) Prescribing Information. https://www.merck.com/product/usa/pi_circulars/s/steglatro/steglatro_pi.pdf. 5. Dekkers CCJ et al. Nephrol
Dial Transplant. 2020;35:i33-i42.
SGLT2i Prescribing Information: Contraindications, Warnings, and Precautions1-4
CANVAS, DECLARE, EMPA-REG, and CREDENCE: Renal Outcomes by eGFR Stratum5
a
eGFR <30 mL/min/1.73 m2
in patients who are being treated for glycemic control without established CVD or CV risk factors.
Contraindications
Do not use in patients with a history of hypersensitivity to this agent
Severe renal impairment, ESKD, or dialysis
Warnings/Precautions
Lower limb amputation in patients with CVD, limb infections, or leg ulcers
Hypotension, volume depletion
Ketoacidosis
AKI or renal impairment
Urosepsis, pyelonephritis
Hypoglycemia risk increases when used with insulin or SU
Fournier’s gangrene
Genital mycotic infections
DAPA
X
Xa
DAPA
X
X
X
X
X
X
Increased LDL-C
Hypersensitivity reactions
Bone fracture
CANA
X
X
CANA
X
X
X
X
X
X
X
X
X
EMPA
X
X
EMPA
X
X
X
X
X
X
X
X
X
ERTU
X
X
ERTU
X
X
X
X
X
X
X
X
X
SGLT2i,
n/N
Trials
Placebo,
n/N
Estimated
NNT per 5 y
Renal outcomes per eGFR stratum, mL/min/1.732
eGFR <45
21/374 14/189 33
Canagliflozin (CANVAS) NA NA 41
Canagliflozin (CREDENCE) 122/678 166/687 8
13
21/606 38/659 31
Empagliflozin (EMPA-REG) 24/822 26/416 18
Canagliflozin (CANVAS) NA NA 61
Canagliflozin (CREDENCE) 58/630 97/636 8
30
Dapagliflozin (DECLARE) 65/3,838 121/3,894 58
Empagliflozin (EMPA-REG) 37/2,406 29/1,232 72
Canagliflozin (CANVAS) NA NA 71
Canagliflozin (CREDENCE) 65/893 77/876 38
Subgroup mean (I2
= 11.7%) 62
Dapagliflozin (DECLARE) 41/4,137 79/4,025 90
Empagliflozin (EMPA-REG) 18/1,043 17/486 39
Canagliflozin (CANVAS) NA NA 47
Subgroup mean (I2 = 0.0%) 79
0.4 0.6 0.8 1.0 1.4 1.61.2
SGLT2i better Placebo better
HR (95% Cl)
0.70 (0.36-1.39)
0.65 (0.29-1.48)
0.71 (0.56-1.89)
0.70 (0.57-0.88)
0.60 (0.35-1.02)
0.42 (0.24-0.73)
0.78 (0.46-1.13)
0.59 (0.43-0.82)
0.60 (0.48-0.74)
0.54 (0.40-0.73)
0.62 (0.38-1.01)
0.58 (0.41-0.84)
0.81 (0.58-1.13)
0.63 (0.52-0.76)
0.50 (0.34-0.73)
0.49 (0.25-0.95)
0.44 (0.25-0.78)
0.48 (0.36-0.64)
Empagliflozin (EMPA-REG)
Subgroup mean (I2
= 0.0%)
eGFR 45-60
eGFR 60-90
eGFR >90
Dapagliflozin (DECLARE)
Subgroup mean (I2
= 0.0%)

8. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. Cherney D et al. Diabetologia. 2020;63:1128-1140. 2. Silverthorn DU. Human Physiology: An Integrated Approach. 5th ed. Prentice Hall; 2009.
LSM Changes From Baseline in eGFR1
SGLT2 Inhibitors and Turboglomerular Feedback2
3.0
2.0
1.0
0
-1.0
-2.0
-3.0
-4.0
-5.0
6 12 18 26 39 52 65 78 91 104
LSMChangeFromBaseline
ineGFR,mL/min/1.73m2
LSMChangeFromBaseline
ineGFR,mL/min/1.73m2
Time, wk
3.0
2.0
1.0
0
-1.0
-2.0
-3.0
-4.0
-5.0
6 12 18 26 39 52 65 78 91 104
Patients With Baseline UACR <3.39 mg/mmol Patients With Baseline UACR ≥3.39 mg/mmol
BL BL
Non-ertugliflozin Ertugliflozin 5 mg Ertugliflozin 15 mg
Ertugliflozin 5 mg
Time, wk
Patients, n
Non-ertugliflozin 489
490
502Ertugliflozin 15 mg
477
475
487
461
467
473
451
464 459
442
436 398
468
426 395
462 444 413
385 358
382 353 341
332
316
408 373
312
359 336
Ertugliflozin 5 mg
Patients, n
Non-ertugliflozin 142
147
126Ertugliflozin 15 mg
140
143
118
136
136
114
134
136 131
134
128 119
112
132 122
111 109 101
114 109
112 106 100
104
95
98 91
97
85 336
1
2
3
4
5
2
3
4
5
GFR increases
Flow through tubule increases
Flow past macula densa
increases
Paracrine from macula
densa to afferent arteriole
Afferent arteriole constricts
1
Efferent arteriole
Glomerulus Distal tubule
Collecting
Proximal
tubule
duct
Loop
of
Henle
Bowman’s capsule
Macula densa
Granular cells
Afferent arteriole
25 Seconds
<40
>45
GFR

9. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. American Diabetes Association. Diabetes Care. 2020;43(suppl 1):S1-S212.
ADA Treatment Algorithm1
First-line therapy is metformin and comprehensive lifestyle modifications (including weight management and physical activity)
Consider independently of baseline A1C
or individualized A1C target
ASCVD predominates
If A1C above target
HF or CKD predominates
If A1C above target
Indicators of high risk or established
ASCVD, CKD, or HF
Compelling need to minimize
hypoglycemia
If A1C above target
If A1C above target
If A1C above target
If A1C above target
If A1C above target
Cost is a major issue
If A1C above target
If A1C above target
To avoid
therapeutic inertia,
reassess and
modify treatment
regularlyNO
• Established ASCVD
• Indicators of high ASCVD
risk (age >55 years with
coronary, carotid, or lower
extremity artery stenosis
>50% or LVH)
Preferably
GLP-1 RA
with proven CVD benefit
or
SGLT2i with proven CVD benefit
if eGFR adequate
If further intensification is
required or patient is now unable
to tolerate GLP-1 RA and/or
SGLT2i, choose agents
demonstrating CV safety:
• For patients on GLP-1 RA,
considering adding SGLT2i
with proven CVD benefit;
DPP-4i if not on GLP-1 RA;
basal insulin; TZD; or SU
• Particularly HFrEF
(LVEF <45%)
• CKD: specifically eGFR
30-60 mL/min/1.73 m2
or UACR >30 mg/g,
particularly UACR >300 mg/g
Preferably
SGLT2i with evidence of reducing
HF/CKD progression in CVOTs if
eGFR adequate
or
If SGLT2i not tolerated/
contraindicated
or if eGFR less than adequate
add GLP-1 RA
with proven CVD benefit
Avoid TZD in the setting of HF;
choose agents demonstrating CV
safety: for patients on SGLT2i,
consider adding GLP-1 RA with
proven CVD benefit; DPP-4i
(not saxagliptin) in the setting
of HF (not on GLP-1 RA);
basal insulin; or SU
DPP-4i GLP-1 RA SGLT2i TZD
SGLT2i
or
TZD
SGLT2i
or
TZD
GLP-1 RA
or DPP-4i
or TZD
SGLT2i
or DPP-4i
or
GLP-1 RA
Continue with addition of other agents
as outlined above
Consider the addition
of SU or basal insulin:
• Choose later-generation SU with lower
risk of hypoglycemia
• Consider basal insulin with lower risk
of hypoglycemia
GLP-1 RA
with good efficacy
for weight loss
SGLT2i
SGLT2i
GLP-1 RA
with good efficacy
for weight loss
If quadruple therapy required, or SGLT2i
and/or GLP-1 RA not tolerated/
contraindicated, use regimen with
lowest risk of weight gain
Preferably
DPP-4i (if not on GLP-1 RAs)
based on weight neutrality
If DPP-4i not tolerated/contraindicated
or patient already on GLP-1 RA, cautious
addition of SU, TZD, or basal insulin
SU TZD
TZD SU
• Insulin therapy: basal insulin
with lowest acquisition cost
or
• Consider DPP-4i or SGLT2i
with lowest acquisition cost
YES
Compelling need to minimize
weight gain or promote weight loss
If A1C above individualized target
proceed as below

10. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. Heerspink HJL et al. Nephrol Dial Transplant. 2020;35:274-282. 2. Wheeler DC et al. Nephrol Dial Transplant. 2020 Aug 30 [Epub ahead of print]. 3. Heerspink HJL et al. Presented at European Society of
Cardiology Congress 2020 (ESC 2020).
The DAPA-CKD Trial1-3
DAPA-CKD Study Design
Inclusion Criteria
ü ≥18 years
ü eGFR ≥25-75
mL/min/1.73 m2
ü UACR 200 to
5,000 mg/g
ü Stable MTD of ACEi
or ARB for ≥4 weeks
(if not contraindicated)
ü Multicenter (~400 sites); target N = 4,300
ü Patients with and without T2DM
• Dapagliflozin 10 mg
• Placebo
• 1:1 randomization
• ~45 months
(median)
• Event-driven
(681 events)
• ≥50% decline
in eGFR
• ESKD
• Renal or CV death
û Polycystic kidney
disease
û Lupus nephritis
û ANCA vasculitis
û T1DM
Exclusion Criteria Interventions Follow-Up Primary Outcome
Stopped
Early for
Efficacy
Primary Outcome
Sustained ≥50% eGFR Decline, ESKD, Renal or CV Death
0
0
2
4
6
8
10
12
14
16
18
20
22
24
4 8 12 16
Time Since Randomization, mo
Hazard ratio, 0.61 (95% CI, 0.51-0.72)
P = .000000028
NNT = 19 Placebo
Dapagliflozin
197 events
312 events
CumulativeIncidence,%
20 24 28 32
2,152 2,001 1,955 1,898 1,841 1,701 1,288 831 309
2,152
Dapagliflozin
No. at Risk
Placebo 1,993 1,936 1,858 1,791 1,664 1,232 774 270
2,152 2,001 1,955 1,898 1,841 1,701 1,288 831 309
2,152
Dapagliflozin
No. at Risk
Placebo 1,993 1,936 1,858 1,791 1,664 1,232 774 270
Secondary Outcome
Sustained ≥50% eGFR Decline, ESKD, Renal Death
0
0
2
4
6
8
10
12
14
16
18
20
22
24
4 8 12 16
Time Since Randomization, mo
Hazard ratio, 0.56 (95% CI, 0.45-68)
P = .000000018
Placebo
Dapagliflozin
142 events
243 events
CumulativeIncidence,%
20 24 28 32

11. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. Heerspink HJL et al. Nephrol Dial Transplant. 2020;35:274-282. 2. Wheeler DC et al. Nephrol Dial Transplant. 2020 Aug 30 [Epub ahead of print]. 3. Heerspink HJL et al. Presented at European Society of
Cardiology Congress 2020 (ESC 2020).
The DAPA-CKD Trial1-3
Summary of the Primary Outcome and Its Components
Placebo
events
Well tolerated; DKA was not reported in any patients receiving DAPA (but in 2 receiving PBO)
Hazard Ratio
(95% CI)
P
Dapagliflozin
events
NC83Transplantation
NC62Renal death
Favors dapagliflozin
Hazard Ratio (95% CI)
Favors placebo
0.3 0.6 1.0 1.4
.20290.81 (0.58-1.12)8065CV death
.00800.66 (0.48-0.90)9968Chronic dialysis
.00450.67 (0.51-0.88)12084eGFR <15 mL/min/1.73 m2
.00040.64 (0.50-0.82)161109ESKD
<.00010.53 (0.42-0.67)201112≥50% eGFR decline
.0000000280.61 (0.51-0.72)312192Primary composite endpoint

12. Show Me the Data: Improving Renal Outcomes
With Glucose-Lowering Therapy in the
Individualized Management of T2DM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/RBT930
1. https://clinicaltrials.gov/ct2/show/NCT03594110.
EMPA-KIDNEY Study Design1
Inclusion Criteria
ü ≥18 years
ü eGFR ≥25-<45
mL/min/1.73 m2
or ≥45-<90
mL/min/1.73 m2
and
UACR ≥200 mg/g
(or protein:creatinine
≥300 mg/d)
ü Multicenter (~7 countries); target N = 6,000
ü Patients with and without T2DM using an ACEi or ARB
ü Estimated completion date is June 2022
• Empagliflozin
• Placebo
• 1:1 randomization,
double-blind
• ~3.1 years (median) • Renal endpoint
– Sustained ↓eGFR
to <10 mL/min/
1.73 m2
– Sustained decline
of ≥40% in eGFR
from randomization
– ESKD
– Renal death
-- or --
• CV death
û Polycystic kidney
disease
û T2DM and ASCVD
with eGFR >60
mL/min/1.73 m2
û Bariatric surgery
Exclusion Criteria Interventions Follow-Up Primary Outcome
Currently
Recruiting