DIABETES GUIDELINES MOA EFFICACY PROTECTION SAFETY BENEFITS &

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 8.5
Diabetes is a Major Health Issue

536.6 Million People are Living Egypt Comes in the Top 10 Countries
Worldwide for Number of Adults
with Diabetes Worldwide (1) with Diabetes in 2021
with 10.9 Million Patients

Rank No.5 for the Number of Adults with

Undiagnosed Diabetes
With 6.8 Million Patients

Diabetes
Prevalence
10.5% of the world’s population (1)

IDF Diabetes Atlas 2021 – 10th edition | www.diabetesatlas.org

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8.5 The Diabetes Drama

Patients with T2D

4×
Globally, 1/3 of patients
4-Fold greater Risk
with T2D have CV disease
of CV Diseases

3× 4×

3 Folds higher mortality from 4 Folds higher mortality from 2/3 of Deaths in people with
Stroke with Type 2 Diabetes CHD with Type 2 Diabetes Type 2 Diabetes is Due to CVD
Analysis of 60 studies with 4,549,481 patients with T2D CV, cardiovascular; T2D, type 2 diabetes Einarson TR et al. Cardiovasc Diabetol 2018;17:83
World J Diabetes v.6(13); 2015 Oct 10 PMC4600176
Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, 1997. Blackwell Sciences

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 Diabetes-Related End-Stage Renal Disease 9

Diabetic
10 Folds more 35% of new
nephropathy 42% of adults with
likely to develop patients beginning
the leading cause ESRD with T2D
T2D have CKD
dialysis therapy
of (ESRD) patients have T2D

#1 10 X

(9) Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–869.

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 Glycemic Targets 11

ADA 2022
 Glycemic Targets

A1C <7.0%(53mmol/mol).
FPG <130 (mg/dl).
2-hr PPG <180 (mg/dl).

ESC 2021
 Glycemic Targets

A1C <7.0%(53mmol/mol).
A1C <6.5%(48mmol/mol).
Should be considered at diagnosis early
in course of T2D in persons who are not
frail or NOT have ASCVD

(11) Diabetes Care Volume 45, Supplement 1, January 2022

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Atcogliflozin A potential Approach in Treatment of T2D a Non Insulin Oral Antidiabetic
Empagliflozin 10,25 mg “SGLT-2 inhibitor”

Empagliflozin

Empagliflozin

Empagliflozin

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 Empagliflozin Monotherapy with Sitagliptin as an Active Comparator
EMPA-REG MONO® in Patients with Type 2 Diabetes

Randomized , Double-Blind,
Parallel-Group, Placebo-
Controlled, Phase 3 Trial

EMPA-REG MONO: study 1245.20

Multicenter
If HbA1c ≥ 7 to ≤ 10% (≥ 53 to ≤ 86 mmol/mol) Placebo (n = 228)
124 sites
Placebo run-in Randomization Empagliflozin 10 mg QD
(2 weeks) (n = 899) (n = 224)
Screening
(n = 1616) Empagliflozin 25 mg QD
Open-label empagliflozin 25 mg QD
24-Weeks (n = 87) (n = 224)

If HbA1c > 10% (> 86 mmol/mol) Sitagliptin 100 mg QD

Enrolled patients (n = 223)

899 Treatment duration Treatment duration

T2D 24 weeks 24 weeks
BMI ≤ 45 kg/m2
Drug-naïve (no oral/injectable anti-
diabetes therapy
For ≤ 12 weeks prior to study)
insufficient glycemic control
BMI, body mass index; HbA1c, glycosylated haemoglobin;QD, once daily; T2D, Type 2 Diabetes.
Roden M, et al. Lancet DiabetesEndocrinol. 2013;1:208–219.

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 Atcogliflozin Optimal Glycemic Control

Atcogliflozin 10 mg & 25 mg showed Significant &

Both doses of Atcogliflozin 10 mg & 25 mg provided Sustained Greater Reductions in FPG than placebo or
Significant Greater HbA1c reductions than placebo or Sitagliptin.
Sitagliptin (HbA1c ≥ 8.5%) at week 24

Adjusted mean (95% CI) change from baseline in

EMPA-REG MONO: study 1245.20

0.5
0

0.01
-0.5
HbA1c (%)

-1

-1.04
-1.5
-1.44 -1.43
-2
Empagliflozin
Placebo 10 mg QD 25 mg QD Sitagliptin

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 Empagliflozin 10 mg & 25 mg showed significant greater reductions in
body weight compared with Sitagliptin or placebo with higher
proportion of Patients reached < 5% Reduction in Bodyweight.
Atcogliflozin Beyond Glycemic Control
Patients with < 5% Reduction in Bodyweight (%)
Atcogliflozin 10 mg & 25 mg provided significant
reductions in SBP compared with placebo or Sitagliptin
4.4% Placebo

Empagliflozin 10 mg
22.8% P > 0.001 P > 0.0001

Adjusted mean change from baseline in SBP (mm Hg)

29.0% Empagliflozin 25 mg
P > 0.001 P > 0.0001
0.7
0.4
6.3% Sitagliptin
P > 0.324

Change From Baseline in Bodyweight (Kg)

- 3.9
-0.33% -2.26% -2.48% +0.18%
- 5.0 Sitagliptin
Placebo Empagliflozin P > 0.355
10 mg QD 25 mg QD
P > 0.0001 P > 0.0001
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 EMPA-REG MET® Empagliflozin as Add-On to Metformin in Patients With Type 2
Diabetes
Randomized , Double-
Blind, Placebo-Controlled,
Phase 3 Trial

Multicenter

EMPA-REG MET: study 1245.23

Placebo QD
148 Centers (n = 207)

1 week 2 weeks If HbA1c ≥ 7 to ≤ 10% Empagliflozin 10 mg QD

(≥ 53 to ≤ 86 mmol/mol) (n = 217)

Randomization Empagliflozin 25 mg QD
24-Weeks Screening Placebo run-in
(n = 970) (n = 214)

Open-label empagliflozin
If HbA1c 10% (> 86 mmol/mol)
Enrolled patients 25 mg QD (n = 69)
638 Treatment duration
24 weeks
T2D (HbA1c 7% to 10%
BMI ≤ 45 kg/m2
Insufficient glycemic control
despite diet & exercise
Stable regimen of IR metformin*
Diabetes Care 2014;37:1650–1659 | DOI: 10.2337/dc13-2105

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 Atcogliflozin Optimal Glycemic Control

Atcogliflozin 10 mg & 25 mg provided significant & sustained reductions in HbA1c compared with placebo
with higher proportion of patients reaching HbA1c level of 7% in Atcogliflozin than with Placebo

Change in HbA1c (%) Change from baseline in HbA1c (%)

at Week 24 Patients Reaching HbA1c >7.0% (%)
Over 24 Week

13%
-0.77 Placebo
-0.70
-0.13 38%
Empagliflozin 10 mg
P > 0.001
P >0.001
p < 0.001
p < 0.001
Empagliflozin
39%
Placebo 10 mg QD 25 mg QD Empagliflozin 25 mg
P > 0.001

Diabetes Care 2014;37:1650–1659 | DOI: 10.2337/dc13-2105

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 Atcogliflozin Optimal Glycemic Control

Atcogliflozin resulted in significant reductions in MDG, FPG & 2-hPPG levels

compared with placebo at week 24.

MDG (mmol/L) FPG (mg/dL) 2-hPPG (mg/dL)

20
10 .
change from baseline in MDG (mmol/L)

6.0

change from baseline in 2-h PPG (mg/dL)

5 10
Empagliflozin 6.3

change from baseline in FPG (mg/dL)

Placebo 10 mg QD 25 mg QD 0
0 Placebo
Placebo -10 -46.0 -44.5
-0.27 -0.87 -1.16 -5
-20
-10 -20.0 -22.3
-30
-15
-40
-20
P = 0.002 P = 0.001 -50
P = 0.001 P = 0.001
-25
P = 0.001 Empagliflozin
P = 0.001 -60
-30 Empagliflozin 10 mg QD 25 mg QD
25 mg QD
10 mg QD

Diabetes Care 2014;37:1650–1659 | DOI: 10.2337/dc13-2105

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 Atcogliflozin Beyond Glycemic Control

Both doses of empagliflozin resulted in

significant reductions in body weight Both doses of Empagliflozin showed significant greater reductions from baseline
compared with placebo. in SBP & DBP at week 24 than placebo

Empagliflozin
Placebo 10 mg QD 25 mg QD
Empagliflozin
0.0
Change From Baseline in Bodyweight (Kg) Placebo 10 mg QD 25 mg QD

change from baseline in DBP (mmHg)

change from baseline in SBP (mmHg)
-0.4

-0.5 -2.1 -2.5

Placebo Empagliflozin
10 mg QD 25 mg QD -4.5
P > 0.001 P > 0.001 P > 0.001 -2.0 -1.6
-5.2 P = 0.006 P = 0.026
P > 0.001

Diabetes Care 2014;37:1650–1659 | DOI: 10.2337/dc13-2105

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 ® Comparison of Empagliflozin and Glimepiride as add-on to
EMPA-REG-H2H-SU Metformin in patients with type 2 diabetes.
Randomised,double-blind,
double dummy manner.
active-controlled, parallel-
group, 2-year trial

EMPA-REG H2H-SU : study

Multicenter
173 Sites 2 weeks Glimepiride
1–4 mg OD
(n = 780)
Randomization
Placebo run-in (n = 1549)
Empagliflozin
104-Weeks
25mg OD
(n = 765)
Enrolled patients Treatment duration
1549
104 weeks
T2D (HbA1c 7% to 10%
BMI ≤ 45 kg/m2
Insufficient glycemic control
despite diet & exercise
Stable regimen of IR metformin*

Lancet Diabetes Endocrinol 2014 Published Online June 16, 2014 http://dx.doi.org/10.1016/ S2213-8587(14)70120-2
Martin Ridderstråle, Knut Robert Andersen, Cordula Zeller, Gabriel Kim, Hans J Woerle, Uli C Broedl, on behalf of the EMPA-REG H2H-SU trial investigators

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 Atcogliflozin Optimal Control On Diabetes and Moreover

Empagliflozin demonstrated significant The reductions in bodyweight were significant and sustained with
reductions in HbA1c compared with Empagliflozin versus an increase with Glimepiride
Glimepiride at Week 24

Adjusted mean change from baseline in HbA1c (%)

-0.55
-0.66
P 0.015

Glimepiride
Empagliflozin

Lancet Diabetes Endocrinol 2014 Published Online June 16, 2014 http://dx.doi.org/10.1016/ S2213-8587(14)70120-2

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 EMPA-REG MET SU® Empagliflozin as Add-on to Metformin Plus Sulfonylurea in
Patients With Type 2 Diabetes
Randomized , Double-
Blind, Placebo-Controlled,
Phase 3 Trial

Multicenter

EMPA-REG MET SU : study

Placebo QD
148 Centers (n = 225)

2 weeks If HbA1c ≥ 7 to ≤ 10% Empagliflozin 10 mg QD

(≥ 53 to ≤ 86 mmol/mol) (n = 226)
Screening
Metformin + Randomization Empagliflozin 25 mg QD
24-Weeks SU
Placebo run-in
(n = 669) (n = 218)
( n= 1010 )
Open-label empagliflozin
If HbA1c 10% (> 86 mmol/mol)
Enrolled patients 25 mg QD (n = 103)
669 Treatment duration
T2D (HbA1c 7% to 10% 24 weeks
BMI ≤ 45 kg/m2
Insufficient glycemic control
despite diet & exercise
Patients inadequately controlled
on metformin and sulfonylurea
DIABETES CARE, VOLUME 36, NOVEMBER 2013

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 Atcogliflozin Optimal Glycemic Control

Atcogliflozin 10 mg & 25 mg provided significant & sustained reductions in HbA1c compared with placebo
with higher proportion of patients reaching HbA1c level of 7% in Atcogliflozin than with Placebo

Placebo 10 mg Empagliflozin 25 mg
Over 24 Weeks At Week 24

Change from baseline in HbA1c (%)

P >0.001
-0.17

-0.82 -0.77 Patients Reaching HbA1c >7.0% (%)

P >0.001

P >0.001

13% 26% 32%

Empagliflozin 10 mg Empagliflozin 25 mg
Placebo

DIABETES CARE, VOLUME 36, NOVEMBER 2013

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 Atcogliflozin Optimal Control On Diabetes and Moreover

Empagliflozin 10 mg and 25 mg shows Both doses of empagliflozin resulted in Empagliflozin 10 mg and 25 mg shows
significant & sustained reductions in HbA1c significant reductions in body weight significantly reduced systolic blood
overtime compared with placebo compared with placebo. pressure versus placebo

Change From Baseline in SBP (mmHg)

Empagliflozin
Change from baseline in MDG (mmol/L) Change From Baseline in Bodyweight (Kg)
Placebo 10 mg QD 25 mg QD

change from baseline in SBP (mmHg)

+0.03 -1.05 -1.14
-1.4

-0.39 -2.16 -2.39

-4.1
Placebo Empagliflozin Placebo Empagliflozin
P > 0.005
10 mg QD 10 mg QD 25 mg QD -3.5
25 mg QD
P > 0.001 P > 0.001 P > 0.001 P > 0.03
P > 0.001

Diabetes Care 2014;37:1650–1659 | DOI: 10.2337/dc13-2105

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 Atcogliflozin Optimal Glycemic Control

Atcogliflozin Proved significant HbA1c Reduction As Monotherapy or Dual Therapy or Triple – Combination
( Open Label Arm).

-2.89 EMPA-REG MET SU

-3.23 EMPA-REG MET

-3.70 EMPA-REG MONO

Roden M, et al. Lancet Diabetes Endocrinol. 2013;1:208–219.

Diabetes Care 2014;37:1650–1659 | DOI: 10.2337/dc13-2105
DIABETES CARE, VOLUME 36, NOVEMBER 2013

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 Atcogliflozin Optimal Glycemic Control

Atcogliflozin Delayed Need for Insulin Initiation in Patients with Type 2 DM & CV Disease: By 60%

60%

•MUTHIAH VADUGANATHAN, NAVEED SATTAR ,Diabetes 2020 Jun; 69

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 Atcogliflozin in addition to standard of care reduced CV risk
Beyond Glycemic Control
and improved overall survival in adults with T2D at high CV risk

↓ All-cause ↓ HHF
38% ↓ CV death 32% mortality 35%
14% ↓ 3P-MACE
p<0.0001 p=0.002
p<0.0001
p=0.04

Atcogliflozin Demonstrated Beneficial Effects on Renal Outcome

46% 39% 38% 44% 55%

P > 0.001 P > 0.001 P > 0.001 P > 0.001 P > 0.04

↓ Composite Renal ↓ Incident/Worsening ↓ Progression to ↓ Doubling of Serum ↓ Initiation of Renal

Outcomes Nephropathy Macroalbuminuria Creatinine Replacement Therapy
Composite renal outcomes {doubling of serum creatinine, initiation of renal replacement therapy or death due to renal disease)
n engl j med 373;22 nejm.org November 26, 2015
2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.

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 10 x Less HYPOGLYCEMIA
Atcogliflozin Showed Proven Safety, Tolerability & Wealth of Evidence

(1)

32%
 Empagliflozin Showed Significantly Lower Risk of Hypoglycemia than Glimepiride. (1) EMPA-REG-H2H-SU

60  Well Tolerated with a Frequency of Hypoglycemia Akin to Placebo.(2) EMPA-REG MONO

mg/dl
 Frequency of UTIs with empagliflozin was comparable to placebo. (2) EMPA-REG MONO

 Significantly Reduced SBP by 4.1–4.8 mmHg, & DBP by 1.6–1.9 mmHg Compared with
placebo without Increases in Pulse Rate.(3) EMPA-REG MET

Atcogliflozin Guidelines Recommendations

Empagliflozin Recommended by ADA 2022 Empagliflozin Recommended by ESC 2021

 For diabetic patients to achieve glycemic goal. (3) For T2D naiive patients on High or very high CV risk
 For Diabetic patients at high risk of CV events . Metformin treated T2D patients.
 For ASCVD, HF & CKD patients with or without albuminuria. ASCVD & HF patients
 To promote weight loss and minimize hypoglycemia . CKD patients

(1) Lancet Diabetes Endocrinol 2014 Published Online June 16, 2014 http://dx.doi.org/10.1016/ S2213-8587(14)70120-2
(4) Diabetes Care Volume 45, Supplement 1, January 2022
(2)Roden M, et al. Lancet Diabetes Endocrinol. 2013;1:208–219.
(3) Häring HU, et al. Diabetes Care. 2014;37:1650–1659.

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 Atcogliflozin Showed Multidimensional Benefits
EFFICACY
Atcogliflozin Proven Optimal Glycemic Control
HbA1c
-0.78 -3.70 -24.5
Double blind – Open Label
Atcogliflozin Efficacy Beyond Glycemic Control
Significant Reduction in Bodyweight (Kg)
Significant Reduction in SBP & DBP (mmHg)
PROTECTION
Atcogliflozin For Diabetes Moreover
Atcogliflozin Reduced CV risk and
FPG Improved CV Outcomes & Overall
Survival in T2D established CV disease
14% Reduction ↓ 3P-MACE
38% Reduction ↓ CV death
-2.48
32% Reduction ↓ All-cause
mortality
SAFETY
 Atcogliflozin Showed Significantly
Lower Risk of Hypoglycemia than
Glimepiride & Akin to Placebo.
 Significantly Reduced SBP & DBP
Compared with placebo without
Increases in Pulse Rate.(3)
DOSAGE & ADMINSTRATION
Convenient Once Daily Dose

SBP -5.0 DBP -1.6 35% Reduction ↓ HHF

Atcogliflozin Demonstrated
WEALTH OF EVIDENCE Beneficial Effects on Renal
Outcome
Atcogliflozin Showed Beneficial Outcomes As Monotherapy,
Reduction ↓ Incident
Or Dual therapy or Triple Combination. 46% / Worsening Nephropathy
Add on to Metformin or Sulphonylurea with/ without Metformin.
(1) Lancet Diabetes Endocrinol 2014 Published Online June 16, 2014 http://dx.doi.org/10.1016/ S2213-8587(14)70120-2
(2)Roden M, et al. Lancet Diabetes Endocrinol. 2013;1:208–219.
39% ↓ Composite Renal Outcomes
(3) Häring HU, et al. Diabetes Care. 2014;37:1650–1659.

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