Expert Summit Meeting

Focus on Dapagliflozin/Sitagliptin Fixed-dose

Combination
Disclaimer

• The content in the slides you are about to see is designed to gain insights and for
consultation purposes and getting advice during the advisory board. It is not for
promotional purpose.

• The use of brand names of drugs, if any, is purely out of habit/convenience and not
for promotional purpose

• This meeting is being recorded but it won't be used for promotional purposes
Welcome to All Advisors
Cipla team
• RBM Name
• ZBM Name
• HO Name
 Objective

• To gain insights on
• The potential and usage of Dapagliflozin/Sitagliptin FDC in clinical practice.

• Preference of SGLT2i/DPP4i in routine practice.

• Seek advise in describing a rationale practical guidance for optimal use of this
combination in T2DM patients with varied comorbidities.
Agenda

Introduction & Agenda Cipla Medical Affairs

Discussion

• Evidence of Dapagliflozin/Sitagliptin
• Expert opinion
70 mins Expert Summit Panel
Using Dapagliflozin/Sitagliptin FDC in the clinical practice

Opinion from the experts

UNDERSTANDING ROUTINE CLINICAL PRACTICE
T2DM INCIDENCES IN CLINICAL PRACTICE

NEWLY T2DM PATIENTS T2DM PATIENTS

DIAGNOSED WITH WITH
T2DM INADEQUATE COMORBIDITIES*
1 PATIENTS 2 GLYCEMIC
CONTROL
3

Q) In your clinical practice, what would be the percentage of

these three patient types?

* Comorbidities of CAD, HF, CKD, HTN, obesity

ADA 2022 Recommendations

 Metformin is the first line medication along with Lifestyle modification

 Antihyperglycemic agent like DDP4i (e.g. Sitagliptin) can be considered when
adequate glycemic control is not achieved with Metformin.
 Early combination therapy can be considered in some patients at treatment initiation to
achieve glycemic target.
 SGLT2i (e.g. Dapagliflozin) must be recommended for individuals with T2DM with
established ASCVD, HF, &/or CKD. 10

Diabetes Care. 2022; 45: S125 – S143

T2DM MANAGEMENT APPROACH IN CLINICAL
PRACTICE
NEWLY T2DM PATIENTS T2DM PATIENTS
DIAGNOSED WITH WITH
T2DM INADEQUATE COMORBIDITIES
1 PATIENTS 2 GLYCEMIC
CONTROL
3

Q) What is your opinion on early initiation with

combination therapy (e.g. Dapa/Metformin or
Dapa/Sita) in these patient types?
 Diabetes Continuum
• As disease progresses, function of B-cells decline - OADs can lose efficacy with prolonged use and a progression from
monotherapy to combination (dual or triple) therapies becomes necessary with the use of injectable insulin in a triple
combination therapy.

OAD- oral antidiabetic drugs; DS – Dapagliflozin/Sitagliptin; DAPA-Dapagliflozin, SITA-

sitagliptin
Indian Journal of Endocrinology and Metabolism: July–Aug 2021 - Volume 25 - Issue 4 - p 342-347
EVIDENCE FROM RCT N = 226 T2DM patients; Single pill
Efficacy of Dapagliflozin addon to sitagliptin Study duration: 48 weeks combinations

Changes in HbA1c from baseline (>8%)

 Strong reduction in HbA1c of ~1.2% SITA +MET +

SITA SITA + MET SITA + DAPA DAPA
0
 Patients achieving HbA1c ≤ 7% were
22% with DAPA addition Vs 12% with -0.2

Changes in HbA1c (%)

placebo
-0.4
-0.4
-0.5
 DAPA addition provided significant -0.6
reduction in body weight ( ─ 2.6 Kg Vs -0.8
+ 0.2 Kg ).
-1

-1.2 -1.1
-1.2
-1.4 P < 0.0001
Doses of drugs
Dapagliflozin (DAPA): 10 mg/day; Metformin (MET) : 1500 mg/day;
Sitagliptin (SITA) : 100 mg/day

Diabetes Care 2014;37:740–750

Evidence from RCT: N = 258 T2DM patients; Fixed dose
Efficacy of Dapagliflozin/sitagliptin FDC Study duration: 16 weeks combination

 Strong reduction in HbA1c of ~1.54% with

FDC of DAPA/SITA.

 Patients achieving HbA1c ≤ 7% were 47%

with DAPA/SITA FDC Vs 25% with SITA

 DAPA/SITA FDC provided significant

reduction in body weight
(-1.31 Kg Vs 0.13Kg).
P < 0.0001

Data from prescribing information, DAPASACH S. Data on File

Sitagliptin + Dapagliflozin
Significantly Greater Glycaemic Reduction

FPG Reduction PPG Reduction

Sitagliptin + Dapagliflozin Sitagliptin Sitagliptin + Dapagliflozin Sitagliptin
0 0
Baseline Baseline Baseline Baseline
178.73 176.48 266.22 259.88
-5 mg/dL mg/dL -10 mg/dL mg/dL
FPG Reduction (mg/dL)

PPG Reduction (mg/dL)

-10 -20

-15 -30
-16.69
-34.88
-20 -40

-25 -50
-11.42 mg/dL -19.65 mg/dL
-28.11 P<0.0001 -54.53 P<0.0001
-30 -60

Data on File; 2022

 Safety Results
• No serious adverse events were reported in the study
• Key adverse events: nasopharyngitis, urinary tract infections, hypoglycaemia, headache,
genital fungal infections, abdominal pain
• No deaths/ hospitalisations during the study

No. of adverse events

Sitagliptin 100 mg + Sitagliptin 100 mg Tablets
Dapagliflozin 10 mg Tablets group
group

Mild 22 12
Moderate 5 2
Total 27 14

N=258 T2DM patients randomized to either dapagliflozin 10 mg + sitagliptin 100 mg or sitagliptin 100 mg for 16 weeks Data on File. 2022
T2DM MANAGEMENT APPROACH IN CLINICAL
PRACTICE
NEWLY T2DM PATIENTS T2DM PATIENTS
DIAGNOSED WITH INADEQUATE WITH
T2DM PATIENTS GLYCEMIC COMORBIDITIES

1 2 CONTROL
3

Q) In your clinical practice, at what stage Q) Besides HbA1c, what are the
do you prefer to prescribe SGLT2i/DPP4i parameters considered while
(e.g. DAPA/SITA) FDC in these patient prescribing SGLT2i/DPP4i (e.g.
types? DAPA/SITA) FDC?
 EVIDENCE FROM RCT (DIVERSITY CVR)
Efficacy of dapagliflozin Vs sitagliptin on cardiometabolic risk factors in Japanese patients with early initiation in
T2DM

349 T2DM patients with HbA1c 7%-10% on metformin Or treatment naive

40% were treatment naive patients

Dapagliflozin 5 -10 mg 24 weeks study Sitagliptin Tablets 50 -100 mg

N=168 N=163

Mean age Mean duration of

Mean body weight Mean HbA1c
58y T2DM
75Kg 8
6Y

Primary Efficacy Endpoint Key secondary outcomes

 Composite of  Changes in Cardio-Renal-metabolic factors
 Glycemic factors (HbA1c, FPG, PPG, plasma insulin)
 Maintenance of HbA1c ≤ 7.0%
 Lipid factors (HCL, LDL)
 Avoidance of hypoglycemia  Body weight
 Body weight loss ≥ 3.0Kg  BP (SBP, DBP)
 Renal factors (creatinine, eGFR)

Data on File; 2022

RESULT: PRIMARY ENDPOINT
Improvement of cardiometabolic risks in patients with early stage T2DM

DAPA SITA
100% 89% 92%
P<0.05
80%

60% 55%
% PATIENTS RESPONDERS

49% 50%
40% P<0.05
24% 20%
20% 14%

0%
TE 0 % ia K
g
S I 7. cem 0
PO y 3.
1 c≤ o gl s≥
M s
CO bA yp o
H h tl
of of h
e ce eig
anc d an y
w
ten v oi od
n B
ai A
M
 RESULT: SECONDARY ENDPOINT

GLYCEMIC CONTROL
Both groups showed similar reduction in HbA1c levels.
50% patients in both groups achieved HbA1c ≤ 7%.

DAPA superior over SITA SITA superior over DAPA

• CARDIORENAL METABOLIC RISK FACTORS • GLYCEMIC FACTORS
• Reduction of body weight -2.8 Vs -0.5 Kg • Glucose variability (MAGE, and CONGA at 2 and
• Fasting plasma insulin − 0.17 vs. 0.17 μU/mL 6 h) assessed using FGM.
• ↑ HDL Cholestrol 0.07 vs. 0.00 mg/dL • Predominantly lower PPG
• ↓ Uric acid -0.5 Vs 0.3 mg/dL

MAGE mean amplitude of glycemic excursion, CONGA continuous overall net glycemic action FGM flash glucose
measurement Fuchigami et al. Cardiovasc Diabetol (2020) 19:1
 EFFECT ON CARDIOVASCULAR OUTCOMES

Diabetes Metab J 2021;45:158-172

 CARDIOVASCULAR BENEFITS
TECOS: SITAGLIPTIN DECLARE TIMI: DAPAGLIFLOZIN

Does not increase the risk of CV outcomes Significant improvement in the MACE and
CVD especially in patients with prior MI
N Engl J Med 2015;373:232-42. Circulation. 2019;139:2537–2541
T2DM MANAGEMENT APPROACH IN CLINICAL
PRACTICE
T2DM PATIENTS T2DM PATIENTS
WITH H/O CV
EVENTS

1 2

Q) What is your opinion on the early initiation with SGLT2i/DPP4i (e.g. DAPA/SITA)
combination to prevent cardiovascular complications in these patient types?
OPINION ON CLINICAL EVIDENCE

Q) What additional evidence would instill confidence among HCPs for this product?

Q) In your opinion, what should be the key points of communication to physicians to

ensure optimal usage of this combination?
Usage of DAPA + SITA in CKD patients

T2DM PATIENTS
WITH CKD Q) What is your opinion on usage of DAPA+
SITA in patients with impaired kidney
function?

Q) What is the eGFR value that needs to be

considered while prescribing DAPA/SITA
FDC?
EXPERT OPINION

Presenter’s Name DD-MM-YEAR Slide No.

 SGLT2i/DPP4i FDC therapies approved by DCGI
Parameters SGLT2i/DPP4i combination

Molecule name DAPA SITA EMPA LINA DAPA SAXA REMO VILDA

FDC Available    

One tablet One tablet One tablet

Dosing To be individualized Once daily Once daily Twice daily

Efficacy studies of FDC    No data in public domain

Safety studies of FDC    No data in public domain

Outcome trial conducted

      X X
(Cardio-renal safety)

Cardiorenal outcomes ↓ ↔ ↓ ↔ ↔ ↑ NO DATA NO DATA

↓ Benefit ↔ Neutrality ↑ Risk

SGLT2i + DPP4i preference in patients with comorbidities

DAPA + SITA DAPA + SAXA EMPA + LINA EMPA + LINA

Diabetes Diabetes Diabetes Diabetes,

1 With risk 2 ASCVD 3 Heart 4 CKD
factors Failure

HTN

OBESITY

Q) Please guide us on your preference of Q) In which aspects does one have an edge over
SGLT2i +DPP4i in these various patient the other SGLT2i/DPP4i combinations used in
types. the clinical practice
Ideal patient profile for DAPA + SITA FDC

Q) In your clinical practice, what would be the

patient characteristic parameters for prescribing
DAPA + SITA combination?
(based on these parameters)
• Age -
• Obesity -
• CVD risk -
• Glycemic status –
• Duration of T2DM -
• Presence of comorbid conditions -
• Others
 DESCRIBING A RATIONALE PRACTICAL
GUIDANCE FOR OPTIMAL USE OF THIS
COMBINATION
Q) What in your opinion would be a rational practical guidance for the appropriate usage of
SGLT2i + DPP4i combinations ?

Guidance on when to initiate

A. Based on glycemic factors
i. Treatment naïve patients
ii. Uncontrolled on monotherapy
iii. Patients presenting high CV risk/CKD

B. Based on comorbidities
iv. CV risk factors like HTN, obesity
v. ASCVD & HF patients
vi. CKD patients
Thank You