This document discusses the use of SGLT2 inhibitors (SGLT2i) in managing diabetes. It presents three case studies of patients with diabetes and cardiovascular complications who may benefit from SGLT2i treatment. It summarizes clinical trial data showing that empagliflozin lowers HbA1c, fasting plasma glucose, body weight, and blood pressure compared to other antidiabetic drugs. Empagliflozin also reduces visceral and subcutaneous fat. The document concludes that SGLT2i like empagliflozin provide glycemic control and cardiovascular benefits and can be considered as an addition to metformin for treating diabetes.

1. SGLT2i in the management of Diabetes
DR. DIBBENDHU KHANRA
MD DNB MRCP (UK)
DM CARDIOLOGY
INTERVENTIONAL CARDIOLOGIST

2. AIIMS, RISHIKESH

3. My Journey so far..

4. NO CONFLICT OF INTERST

5. Case 1
• 50 YR MALE
• DCM PATIENT. EF 30%
• DM FOR 5 YEAR, WELL CONTROLLED WITH GLIMEPERIDE
• DIURETICS, BB, ACEI
• HOSPITALISED WITH HEART FAILURE
• WHICH ADD?

6. Case 2
• 40 YR MALE
• HTN
• STEMI
• PPCI TO LAD
• EF 35%
• RECENT ONSET DM
• WHICH ADD?

7. Case 3
• 45 YR obese LADY
• Started on strict dieting
• HTN DM ON GLIPTANS
• CAS CSA CCS2
• OMT
• WHICH ADD?

8. Framingham Offspring Study
Ingelsson E et al. Diabetes. 2007 Jun;56(6):1718-26.
Patients without
DM / Met-S
Patients with
Diabetes
Prevalence of
Subclinical CVD
29.8% 70.4%
Inferences of Study Findings
 Over 2/3rd of patients of DM have Subclinical CVD
 DM ↑ses the Risk of Subclinical CVD by 4.3-fold
(age- and sex-adjusted Odds Ratio: 4.33, p<0.0001)
 Subclinical CVD ↑ses the Risk of CV event by ≈2-fold

9. HFrEF: Hazard Ratio 1.6
95% CI 1.44 - 1.77
p<0.0001
No diabetes (HFrEF)
Cumulativeincidence(%)
60
40
20
0
0 0.5 1 1.5 2 2.5 3 3.5
Follow-up (years)
Diabetes
(HFrEF)
No diabetes (HFpEF)
Diabetes (HFpEF)
Diabetes Increases Risk of
Hospitalization or Death due to Heart-failure
HFrEF: heart failure with reduced ejection fraction
HFpEF: heart failure with preserved ejection fraction
HFpEF: Hazard Ratio 2.0
95% CI 1.70 - 2.36
p<0.0001
MacDonald et al. Eur Heart J 2008;29:1377-85.

10. ARMAMENTORIUM OF ADD
• SU
• METFORMINS
• TZD
• ACARBOSE
• GLIPTANS
• LIRAGLUTIDE
• SGLT2I
• INSULIN
WHICH ONE?

11. Hypo-
glycemia
Weight
Change
CV Effects Renal Effects
ASCVD CHF Progression of
DKD
Dosing /
Use
Metformin No Neutral
(potential for
modest loss)
Potential
benefit
Neutral Neutral Contra-
indicated in
eGFR <30#
SGLT2
inhibitors
No Loss Benefit*
(Empagliflozin,
Canagliflozin)
Benefit
(Empagliflozin,
Canagliflozin)
Benefit
(Empagliflozin,
Canagliflozin)
Contra-
indicated in
eGFR <45#
SUs
(2nd
generation)
Yes Gain Neutral Neutral Neutral Glipizide,
glimepiride
avoid hypo-
glycemia#
DPP4
inhibitors
No Neutral Neutral Potential Risk
Saxagliptin
Alogliptin
Neutral Require
renal dose-
adjustment#
Clinical Considerations for Antidiabetic Agents
*Empagliflozin: Only OAD approved for CV Mortality benefit in T2DM with CVD
Adapted from: ADA Standards of Medical Care in Diabetes. Diabetes Care. 2018; 41(Suppl 1):s1 – s153.
# Refer to locally approved prescribing information of individual agents

12. American Diabetes Association (ADA)
Standards of Medical Care in Diabetes - 2018
Recommendation for Patients with T2DM and
Established Atherosclerotic CVD*
Agent MACE
Reduction
CV Mortality
Reduction
Empagliflozin
+
(Level A)
+
(Level A)
Canagliflozin
+
(Level C)
Not
Recommended
Dapagliflozin
Not
Recommended
Not
Recommended
Liraglutide
+
(Level A)
+
(Level A)
Semaglutide
Not
Recommended
Not
Recommended
*Consider Drug-specific and Patient factors before use
Lifestyle + Metformin

13. ADA AND EASD 2018

16. SGLT2I
GLU EXCRETION
80g
U Na excretion
H20 excretion
500ml
Osmotic diuresis
Helps in HF hemoconc
HCT increases
Exclude
Low vol status
PAD hyperK
Low Serum Glu
(glu dependent)
So no hypo
High glucagon
Calories reduced
240 KCal
Reduces body wt
Total Body water
redcued
Post HypoTN
more Na
delivered to
macula densa
RAAS inhibition
Aff art dilation
eGFR reduced
Creat elevates
(25-30%) thormbus
PTH
FGF23
Increased
# in elderly
Ketones more
DKA
Fat
accumultaion
in myocardium
is replaced by
available
ketones
Helps in
Diab CMP
Decreased
vascular
stiffness
Reduces
albuminuria
UTI
Polyurea
BP lowers
Lowers
uric acid
Early morning
BP surge
reduced
Lipids increase?
SAVES FROM
WORSENING OF
RENAL FUNCTION

18. Met + Pio4
Empagliflozin Provides Consistent Efficacy at Different Stages of
Disease
-0.1
-0.7
-0.8-1
-0.8
-0.6
-0.4
-0.2
0
0.08
-0.7 -0.8
-1.44 -1.43-2
-1.5
-1
-0.5
0
0.5
Placebo
(n = 228)
10 mg QD
(n = 224)
25 mg QD
(n = 224)
10 mg
(n=54)
25 mg
(n=45)
Adjustedmean(95%CI)change
from
baselineinHbA1c(%)
Monotherapy1
7.91 7.87 7.86 9.16 9.18
Placebo
(n = 207)
10 mg QD
(n = 217)
25 mg QD
(n = 213)
Add on to met2
7.90 7.94 7.86
(1) Roden M, et al. Lancet Diabetes
Endocrinol. 2013;1:208–219 (2) Häring HU,
et al. Diabetes Care. 2014;37:1650–1659.
Häring H-U, et al. Diabetes Care.
2013;36:3396–3404 (4) Kovacs C, et al.
Diabetes Obes Metab. 2014;16:147–158 P:
< 0.05
-0.17
-0.8 -0.8
-0.1
-0.6
-0.7-0.9
-0.8
-0.7
-0.6
-0.5
-0.4
-0.3
-0.2
-0.1
0
Placebo
(n = 207)
10 mg QD
(n = 217)
25 mg QD
(n = 213)
Placebo
(n = 155)
10 mg QD
(n = 151)
25 mg QD
(n = 160)
Met + SU3
8.15 8.07 8.10 8.16 8.07 8.06
*
*
* *
*
*
* *
* *

19. Efficacy Empagliflozin in pivotal trials - 24 and 76 week
Monotherapy 1 Add on to Pio 3 Add on to Met + SU 4
India Pt no. N =24 N =29 N=69 N=65 N=9 N=6
B’line HbA1c 8.35 8.09 8.14 8.24 8.4 8.9
Mean A1c change -0.60 -0.99 -0.60 -0.78 -1.60 -1.53
MET, metformin; PIO, pioglitazone; QD, once daily; SU, sulphonylurea. * All data are placebo-corrected and statistically significant unless otherwise marked. 1. Hach T, et
al. Diabetes. 2013;62(suppl 1A);A21 (P69-LB); 2. Roden M, et al. Lancet Diabetes Endocrinol. 2013;1(3):208–219; 3. Häring H-U, et al. Diabetes Care. 2014 (in press); 4.
Kovacs C, et al. Diabetes Obes Metab. 2014;16(2):147–158; 2014;16:147–158 P: < 0.05
Empagliflozin 10 mg QD
Empagliflozin 25 mg QD
Indian Pt No N=24 N=29 N=69 N=65 N=9 N=6
Baseline HbA1c 8.35 8.09 8.24 8.26 8.39 8.90
Mean change in HbA1c -0.81 -1.11 -0.75 -0.78 -1.70 -1.4
24 wk
76 wk
* * * * * *
******

20. FPG (mg/dL) reduction in pivotal trials - 24 week
-31.20
-26.49
-23.40
-23.4
-28.20
-36.20
-28.65 -28.44 -28.44
-29.50
-40
-30
-20
-10
0
Adjusted mean
(SE) difference
vs placebo in
change from
baseline in FPG
(mg/dL)
2014;16:147–158 P: < 0.05
BL, baseline; MET, metformin; PIO, pioglitazone; QD, once daily; RI, renal impairment; SE, standard error; SU, sulphonylurea. * All data are placebo-corrected and statistically significant unless otherwise marked. 1. Hach T,
et al. Diabetes. 2013;62(suppl 1A);A21 (P69-LB); 2. Roden M, et al. Lancet Diabetes Endocrinol. 2013;1(3):208–219; 3. Häring H-U, et al. Diabetes Care. 2014 (in press); 4. Kovacs C, et al. Diabetes Obes Metab.
2014;16(2):147–158; 5. Häring H-U, et al. Diabetes Care. 2013;36(11):3396–404; 6. Rosenstock J, et al. Diabetologia. 2013;56(suppl 1);S372 (P931); 7. Barnett A, et al, Lancet Diabetes Endocrinol. 2014;
doi:10.1016/S2213-8587(13)70208-0.
Monotherapy Add-on to
MET
Add-on to
PIO
Add-on to
MET+SU
N value
Baseline FPG
224 224 217 213 165 168 225 216 169 155
152.79 152.61 154.59 149.37 151.92 151.74 150.84 156.42 138 146
Empagliflozin 10 mg QD Empagliflozin 25 mg QD
*
*
*
*
*
* * *
Add-on to
Basal
insulin

21. -1.93
-1.63
-1.95
-1.76
-2.90
-2.15 -2.01
-1.81
-1.99
-2.80
-3.0
-2.0
-1.0
0.0
Empagliflozin is not indicated for weight loss.
Weight change was a secondary endpoint in clinical trials
Adjusted mean
difference vs
placebo in change
from
baseline in body
weight (kg)
N value
Baseline Wt
Body weight (kg) reduction in pivotal trials-24 wk
224 224 217 213 165 168 225 216 169 155
78.4 77.80 81.6 82.2 78.0 78.90 77.1 77.5 91 94
Mono 1 Add-on to
Met 2
Add-on to
Pio 3
Add-on to
Met + SU 4
MET, metformin; PIO, pioglitazone; QD, once daily; SU, sulphonylurea. * All data are placebo-corrected and statistically significant unless otherwise marked. 1. Hach T, et al. Diabetes. 2013;62(suppl 1A);A21
(P69-LB); 2. Roden M, et al. Lancet Diabetes Endocrinol. 2013;1(3):208–219; 3. Häring H-U, et al. Diabetes Care. 2014 (in press); 4. Kovacs C, et al. Diabetes Obes Metab. 2014;16(2):147–158;
Empagliflozin 10 mg QD Empagliflozin 25 mg QD
Add-on to
Basal insulin4

22. 17.7
-22.3
-40
-30
-20
-10
0
10
20
30
40
11.2
-11.0
-30
-20
-10
0
10
20
30
CI, confidence interval; EMPA, empagliflozin; H2H, head-to-head; QD, once daily.
*Dedicated sub-study using magnetic resonance imaging; patient participation was optional.
Ridderstråle M, et al. Lancet Diabetes Endocrinol. 2014;2:691‒700.
Change in Visceral and Subcutaneous Fat at 2 years*
vs. Glimepiride
Glimepiride
(n = 34)
Empagliflozin
(n = 39)
Glimepiride EMPA 25 mg QD
Mean baseline
(95% CI)
174.4
(143.3, 205.5)
156.7
(138.6, 174.8)
Glimepiride EMPA 25 mg QD
Mean baseline (95%
CI)
337.0
(297.8, 376.2)
346.3
(312.5, 380.2)
-22.2 cm3
(95% CI:
-37.1, -7.4)
p = 0.0039
-40.0 cm3
(95% CI:
-58.9, -21.1)
p < 0.0001
Mean(95%CI)changefrombaselinein
abdominalvisceraladiposetissue(cm3)
Mean(95%CI)changefrombaselinein
subcutaneousadiposetissue(cm3)
Glimepiride
(n = 34)
Empagliflozin
(n = 39)

23. Poster: SA-PO1101, American Society of Nephrology (ASN) Kidney Week, 11–16 November 2014, Philadelphia, PA, USA
Change in SBP, DBP and PP across Various Baselines

24. -2.5
-7.0
-7.7-9
-8
-7
-6
-5
-4
-3
-2
-1
0
Placebo(n = 501) 10 mg QD (n = 517) 25 mg QD (n = 506)
Adjustedmean(SE)changefrom
baselineinSBP(mmHg)
BP, blood pressure; DBP, diastolic blood pressure; QD, once daily; SBP, systolic blood pressure; SE, standard error.
Comparisons versus placebo: *p < 0.001. **p = 0.0152. ***p = 0.1059. FAS (LOCF).
Hach T, et al. Diabetes. 2013;62(suppl 1A):A21 (P69-LB). Data on file.
Phase III Pooled Risk Factor Analysis: Change from Baseline in SBP
by BP Control at Baseline
Patients with uncontrolled BP
(SBP ≥ 130 mmHg and DBP ≥ 80 mmHg)
Mean baseline SBP (mmHg)
136.3 136.9 137.4
*
*
Empagliflozin 10 mg QD
Empagliflozin 25 mg QD
Placebo

25. CI, confidence interval; QD, once daily; SE, standard error. ANCOVA (TS). Hach T, et al. Diabetes. 2013;62(suppl 1A):A21 (P69-LB). Data on file.
Phase III Pooled Efficacy and Cardiovascular Risk Factor Analysis
Change from Baseline in Uric Acid
1.0
-28.9 -29.5
-35
-30
-25
-20
-15
-10
-5
0
5
Placebo (n = 825) 10 mg QD (n = 830) 25 mg QD (n = 820)
Adjustedmean(SE)changefrombaseline
inuricacid(μmol/L)
Mean baseline uric acid (μmol/L)
321.4 321.8 322.4
-30.0
(95% CI:
-35.0, -24.9)
p < 0.0001
-30.6
(95% CI:
-35.7, -25.5)
p < 0.0001
Empagliflozin
Comparison with placebo

26. CI, confidence interval; gMean, geometric mean; SD, standard deviation; UACR, urine albumin-to-creatinine ratio.
*p < 0.001. **p < 0.01. Adjusted gMean based on ANCOVA with LOCF imputation (95% CI); data following a change in anti-hypertensive medication and after glycaemic rescue therapy were excluded.
Cherney D, et al. Abstract accepted at ADA 2014.
Effect of Empagliflozin on Microalbuminuria
Change in UACR at Week 24
Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Mean (SD) baseline UACR (gMean) 68.2 (64.9) 64.6 69.3
Mean (95% CI) UACR at Week 24 (gMean) 53.6 (46.5, 61.7) 37.6 (32.5, 43.4) 40.0 (34.8, 46.0)
P < 0.001 P < 0.01
gMeanchangeinUACRfrom
baseline
(mg/gcreatinine)
Ratio of relative change vs placebo at
Week 24
Empagliflozin
-14.6
-27.0
-29.3
-35
-30
-25
-20
-15
-10
-5
0
10 mg QD
(n = 141)
Placebo
(n = 147)
25 mg QD
(n = 150)

27. Hypoglycaemic events
Phase III safety and tolerability analysis
MET, metformin; PIO, pioglitazone; QD, once daily; SU, sulphonylurea.
†Confirmed events; plasma glucose ≤ 70 mg/dL and/or requiring assistance 1. Hach T, et al., 2. Roden M, et al., 3. Häring H-U, et al.
Diabetes. 2013;(suppl 1):(P69-LB, 1085-P and 1092-P, respectively);
4. Kovacs C, et al. Diabetes Obes Metab. 2014;16:147–158.
0.8 0.4 0.5
1.8
2.9
8.4
1.2
0.4
1.8 1.2
5.2
16.1
1.3
0.4
1.4
2.4
4.0
11.5
0
4
8
12
16
20
Pooled data
excl. SU
background
Monotherapy Add-on to MET Add-on to PIO Pooled data
incl. SU
background
Add-on to MET
+ SU
Percentageofpatientswith
confirmedhypoglycaemia†(%) Placebo
Empagliflozin 10 mg QD
Empagliflozin 25 mg QD
1
2 3 4
1 1

28. Events consistent with UTI-Stratified by gender
Phase III pooled† safety and tolerability analysis
QD, once daily; UTI, urinary tract infection.
†The following studies were included in the pooled analysis: Roden M, et al. Lancet Diabetes Endocrinol. 2013;1(3):208–219 (EMPA-REG MONO); Häring H-U, et
al. Diabetes Care. 2014 (EMPA-REG MET - in press); Kovacs C, et al. Diabetes Obes Metab. 2014;16(2):147–158 (EMPA-REG PIO;
Häring H-U, et al. Diabetes Care. 2013;36(11):3396–404 (EMPA-REG METSU);
Kim G, et al. Diabetes. 2013;(suppl 1):(P74-LB).
Male vs female patients
8.2
13.0
3.8
9.3
18.5
1.9
7.5
15.9
1.1
0
5
10
15
20
25
30
All patients with events Female patients Male patients
Patientswithevents
consistentwithUTI(%) Placebo
(n = 401/424)
Empagliflozin 10 mg QD
(n = 367/463)

29. Events consistent with UTI
Distribution of events severity
Phase III pooled† safety and tolerability analysis
QD, once daily; UTI, urinary tract infection. The intensity of the adverse event was to be judged by the investigator as mild
(awareness of signs or symptoms which were easily tolerated), moderate (enough discomfort to cause interference with usual activity)
or severe (incapacitating or causing inability to work or to perform usual activities).
†The following studies were included in the pooled analysis: Roden M, et al. Lancet Diabetes Endocrinol. 2013;1(3):208–219 (EMPA-REG MONO); Häring H-U, et al. Diabetes Care. 2014 (EMPA-REG MET - in press); Kovacs
C, et al. Diabetes Obes Metab. 2014;16(2):147–158 (EMPA-REG PIO;
Häring H-U, et al. Diabetes Care. 2013;36(11):3396–404 (EMPA-REG METSU);
Kim G, et al. Diabetes. 2013;(suppl 1):(P74-LB).
6.9
1.1
0.2
7.5
1.7
0.1
6.7
0.9
0
0
1
2
3
4
5
6
7
8
Mild Moderate Severe
Patients(%)
Placebo
(n = 825)
Empagliflozin 10 mg QD
(n = 830)
Empagliflozin 25 mg QD
(n = 822)
For Internal use only

30. 0.02
0.00
0.03
0.00
0.04
0.08
0.07
-0.11
-0.04
0.110.10
0.07
-0.02
-0.01
0.16
-0.20
-0.10
0.00
0.10
0.20Adjustedmean(SE)change,
mmol/L
Placebo (n = 825)
Empagliflozin 10 mg QD (n = 830)
Empagliflozin 25 mg QD (n = 822)
Change in Lipids from Baseline at Week 24
Phase III pooled‡ efficacy analysis
HDL-C, high-density lipoprotein cholesterol;
LDL-C, low-density lipoprotein cholesterol; QD, once daily; SE, standard error. *p < 0.05; **p < 0.001; ***p = 0.008 vs placebo. ANCOVA. TS.
†LDL/HDL-C ratio does not have units. ‡The following studies were included in the pooled analysis: Roden M, et al. Lancet Diabetes Endocrinol. 2013;1(3):208–219 (EMPA-REG MONO); Häring H-U, et al. Diabetes Care. 2014 (EMPA-
REG MET - Tin press); Kovacs C, et al. Diabetes Obes Metab. 2014;16(2):147–158 (EMPA-REG PIO;
Häring H-U, et al. Diabetes Care. 2013;36(11):3396–404 (EMPA-REG METSU);
Hach T, et al. Diabetes. 2013;62(suppl 1A):A21 (P69-LB).
LDL-C HDL-C Triglyceride LDL/HDL-C ratio† Total cholesterol
Mean baseline 2.62 2.57 2.57 1.26 1.26 1.27 1.86 1.95 1.96 2.18 2.11 2.11 4.70 4.67 4.70
***
****
*
**

31. EMPA-REG Outcome
• Study medication was given in addition to standard of care
• Glucose-lowering therapy was to remain unchanged for first 12 weeks
• Treatment assignment double-blinded
• The trial was to continue until at least 691 patients experienced
an adjudicated primary outcome event
Zinman B et al. N Engl J Med 2015;doi:10.1056/NEJMoa1504720
Screening
(n=11,531)
Randomised
and treated
(n=7020)
Pooled
Stable background glucose-
lowering therapy
Background glucose-lowering therapy adjustment allowed
to achieve glycaemic equipoise
Empagliflozin 10 mg
(n=2345)
Empagliflozin 25 mg
(n=2342)
Placebo
(n=2333)
SGLT2:1 >2500

32. Primary outcome 3P-MACE: death from CV causes, non-fatal MI or
non-fatal stroke
Relative risk reduction (RRR) for 3P-MACE is 14%; absolute risk reduction (ARR) 1.6% rates of 3P-MACE: 10.5% (empagliflozin) vs. 12.1% (placebo). Cumulative incidence
function. *Two-sided tests for superiority were conducted (statistical significance was indicated if p≤0.0498)
CI, confidence interval; HR, hazard ratio. Empagliflozin is not indicated for CV risk reduction
Zinman B et al. N Engl J Med 2015;doi:10.1056/NEJMoa1504720; Zinman B. EASD 2015; Oral presentation
HR 0.86
(95.02% CI 0.74, 0.99)
p=0.04* 15%

33. CV death
*nominal p-value
Cumulative incidence function. RRR for CV death is 38%; ARR for CV death is 2.2%; rates of CV death: 3.7% (empagliflozin) vs. 5.9% (placebo).
Empagliflozin is not indicated for CV risk reduction. HR, hazard ratio
Zinman B et al. N Engl J Med 2015;doi:10.1056/NEJMoa1504720
HR 0.62
(95% CI 0.49, 0.77)
p<0.001* 33%

34. Hospitalisation for Heart Failure
*Nominal p-value
Cumulative incidence function. HR, hazard ratio
RRR for HHF is 35%; ARR for HHF is 1.4%, rates of HHF: 2.7% (empagliflozin) vs. 4.1% (placebo)
Zinman B et al. N Engl J Med 2015;doi:10.1056/NEJMoa1504720
HR 0.65
(95% CI 0.50, 0.85);
p=0.002*
35%

35. All-cause Mortality
*Nominal p-value. Kaplan–Meier estimate
RRR for all-cause mortality is 32%; ARR for all-cause mortality is 2.6%; rates of all-cause mortality: 5.7% (empagliflozin) vs. 8.3% (placebo)
Empagliflozin is not indicated for CV risk reduction. HR, hazard ratio
Zinman B et al. N Engl J Med 2015;doi:10.1056/NEJMoa1504720
HR 0.68
(95% CI 0.57, 0.82)
p<0.001* 35%

36. New Onset or Worsening Nephropathy
Kaplan-Meier estimate. Patients treated with at least one dose of study drug. Hazard ratios are based on Cox regression analyses. HR, hazard ratio; CI, confidence
interval.
39%
RRR

37. New Onset or Worsening Nephropathy:
Consistent Benefit for Both Doses
Kaplan-Meier estimate. Patients treated with at least one dose of study drug. Hazard ratios are based on Cox regression analyses. HR, hazard ratio; CI, confidence
interval.

38. New Onset of Macroalbuminuria
Kaplan-Meier estimate in treated set.
Hazard ratios are based on Cox regression analyses.
HR 0.62
(95% CI 0.54, 0.72)
p<0.0001
38%
RRR

39. First initiation of continuous renal replacement therapy or
dialysis
Kaplan-Meier estimate in treated set.
Hazard ratios are based on Cox regression analyses.
HR 0.45
(95% CI 0.21, 0.97)
p=0.0409
55%
RRR

40. Declare TIMI 58
• Dapagliflozin
• Bladder Ca rare
• 3PMACE 15% DROP
• HHF 30% DROP
• CV DEATH NOT STATISTICALLY SIGN DROP
• CVD REAL ongoing
SGLT2:1 >1200

41. CANVAS
• Canaglifozin
• Hyperkalemia
• Bone # NNH 1/96 (3 yrs)
• Amputation NNH 1/115 (3 yrs)
• 3P MACE, HHF, CV death none statistically significant
• ONGOING CREDENCE
• FDA Recently approved in HF
SGLT2:1 >250

42. IN THE PIPELINE

43. Case 1
• 50 YR MALE
• DCM PATIENT. EF 30%
• DM FOR 5 YEAR, WELL CONTROLLED WITH GLIMEPERIDE
• DIURETICS, BB, ACEI
• HOSPITALISED WITH HEART FAILURE
• WHICH ADD?
• SGLT2I
• OPTIMIZE DU

44. Case 2
• 40 YR MALE
• HTN
• STEMI
• PPCI TO LAD
• EF 35%
• RECENT ONSET DM
• WHICH ADD?
• SGLT2I after 6 weeks cooling period
• OPTIMIZE antiHTNives

45. Case 3
• 45 YR obese LADY
• Started on strict dieting
• HTN DM ON GLIPTANS
• CAS CSA CCS2
• OMT
• WHICH ADD?
• SGLT2I
• Caution: Fasting

47. BEST CLINICAL PRACTICE: CAUTION!
• Elderly
• Moderate to Severe CKD (eGFR <45mL/min/1.73 m2)
• HYPERKALEMIA
• H/O DKA
• Acute stressful states
• Hypotension
• Risk of volume depletion (diuretics)
• Complicated UTIs: temporary discontinuation recommended
• Conditions of fasting: precipitation of DKA
• ABPI<0.9
• Osteoposis (DEXA SCAN), History of bone #
Adapted: Rajput R, Ved J. Diabetes Metab Syndr. 2017 Mar 31. pii: S1871-4021(17)30016-4.

48. NOT TO WORRY IF
• Creat increases by <25%
• Post hypoTN
• Polyurea
• Hct increases by <25%
• Lipids increases

49. Summary
• 1st choice in cardiac patients
• Class effect in HF patients
• No hypoglycemia
• HBAIC reduction
• Prevents renal deterioration
• Reduces uric acid
• Reduces BP. Prevents LV remodelling
• Also add-ons
• Practice caution. In elderly
• Not to worry if creat increases initially

50. Thank You!