ŠTA SVE (NE)ZNAMO O

OAD
Prof.dr Dragana Tomić Naglić, endokrinolog, UKC Vojvodina
datum: 28.11.2022.
Ovo predavanje je sponzorisano od strane kompanije
Servier d.o.o
 Dijabetes i dalje veliki izazov u svetu
North America & Caribbean Europe
2045 63 million 2045 69 million
2030 57 million
24% 2030 67 million
13%
increase increase
2021 51 million 2021 61 million
WORL
D
2045 783
South & Central America Western Pacific million
2045 49 million 2045 260 million 643 46%
2030 40 million
50% 2030 238 million
27% 2030
million increase
increase increase
2021 32 million 2021 206million 537
2021
million

Africa Middle East & North Africa South-East Asia

2045 55 million 2045 136 million 2045 152 million
2030 33 million
134% 2030 95 million
87% 2030 113 million
68%
increase increase increase
2021 24million 2021 73 million 2021 90 million

Number of people (20-79 years) with diabetes globally and by IDF Region
IDF Atlas, 10th Edition, 2021
 Alarmantan % nedijagnostikovanih pacijenata sa dijabetesom (20-79g) u
zemljama niskog i srednjeg razvoja

36
%
Skoro 1 od 2 (44,7%) Europ
e
odrasla živi sa dijabetesom
a da toga nisu ni svesni 24
% 53%
NA W
C Pacific
33
%
SAC 38% 51
A
54% %
SE
MENA
Asia
87.5% u zemljama
Africa
Abbreviations: AFR, Africa région; EUR, Europe; MENA, Middle East and North Africa; NAC, North America and Carribean; SACA, South
America and Central America; SEA, South-East Africa; T2D, type 2 diabetes; WP, Western Pacific. EMG, emerging markets; EST, established
niskog i srednjeg
razvoja
markets; T2D, Type 2 Diabetes; HI High Income; MI, Middle Income; LI, Low Income
IDF Region. IDF Atlas, 10th Edition, 2021; Saeedi P et al. Diabetes Res Clin Pract. 2020 -4-
 I dalje povećana smrtnost usled dijabetesa u svetu

1/3 svih smrtnih slučajeva zbog dijabetesa

javlja se kod ljudi <60 godina

8%
Dijabetes je odgovoran za Europe

12%
6.7 milliona smrti u 2021 Worldwide

(1 smrt na svakih 5 sekundi) 18%

NAC 15%
W Pacific

8%
SACA
25% 9% 7%
MENA Africa SE Asia
Abbreviations: AFR, Africa région; EUR, Europe; MENA, Middle East and North Africa; NAC, North America and Carribean;
SACA, South America and Central America; SEA, South-East Africa; T2D, type 2 diabetes; WP, Western Pacific. EMG, emerging
markets; EST, established markets; T2D, Type 2 Diabetes; HI High Income; MI, Middle Income; LI, Low Income
IDF Region. IDF Atlas, 10th Edition, 2021; Saeedi P et al. Diabetes Res Clin Pract. 2020
-5-
 Rano lečenje T2D smanjuje smrtnost
NEW UKPDS DATA
KOJA SU NOVA SAZNANJA?

Svako povećanje HbA1c za 1% povećava rizik od smrti

 18% na 10 godina
 36% na 20 godina

Odlaganje početka lečenja ima dramatičan uticaj na smrtnost

• Ako je HbA1c smanjen od dijagnoze: Mortalitet 18.8%

• Ako se smanjenje HbA1c odloži za 5 do 10 godina: Mortalitet 2.7%

Lind M. et al.; Historical HbA1c Values May Explain the Type 2 Diabetes Legacy Effect: UKPDS 88. Diabetes Care 2021; 44 (10): 2231–2237. https://doi.org/10.2337/dc20-2439
Bolja kontrola glikemije manje komplikacija

Mikrovaskularne
UKPDS: Svaki pad HbA1c za samo 1%, smanjuje 37% komplikacije
rizik od razvoja komplikacija dijabetesa za:

Amputacije stopala
43%
HbA1c

1%
21% Smrtni slučajevi povezani sa
dijabetesom

14% Infarkt srca

12% Moždani udar

Stratton IM, et al. BMJ. 2000;321(7258):405-412.

Strategija lečenja dijabetesa

Cardiovascular Disease and Risk Management:

Standards of Medical Care in Diabetes - 2022. Diabetes Care 2022;45(Suppl. 1):S144-S174
Makrovaskularne komplikacije – faktor rizika koji prednjači je
HbA1c
Relative importance of risk factors for predicting acute MI among patients
with T2DM, with or without pre-existing conditions (N=271,174)
All patients Patients without coexisting conditions at baseline
Glycated haemoglobin Glycated haemoglobin
Systolic blood pressure LDL cholesterol
LDL cholesterol Systolic blood pressure
Physical activity Smoking
Smoking Physical activity
Duration of diabetes Estimated GFR
Estimated GFR Duration of diabetes
Income Income
Diastolic blood pressure Diastolic blood pressure
Heart failure Marital status
Blood pressure medication Education
Marital status Blood pressure medication
Education Albuminuria
Albuminuria Immigrant
Lipid-lowering medication Lipid-lowering medication
Immigrant Body mass index
Atrial fibrillation
Body mass index
R2 R2
0.000 0.005 0.010 0.015 0.020 0.000 0.005 0.010 0.015 0.020

Increasing importance Increasing importance

GFR, glomerular filtration rate; HbA1c, glycated haemoglobin; LDL, low-density lipoprotein; MI, myocardial infarction; R , relative risk; T2DM, type 2 diabetes mellitus.
2
9
Rawshani A, et al. N Engl J Med. 2018;379(7):633-44.
Faktori koje bi trebalo uzeti u obzir prilikom postizanja dobre
glikoregulacije

Adaptirano Inzzucchi, Diabetes Care, 2015

 Za većinu pacijenata na monoterapiji metforminom,
izazov je postići glikemijske ciljne vrednosti

55%
Pacijenti na
monoterapiji sa HbA1c
>6,5 (%)

55

Pacijenti sa HbA1c>6,5% Pacijenti sa HbA1c<6,5%

 Preko polovine pacijenata na monoterapiji metforminom, ne postignu

Yurgin N et al. Clin Therapy 2007; 29:316-25. ciljne vrednosti
Broj pacijenata koji su kontrolisani na metforminu nakon
postizanja inicijalnog HbA1c < 6,5%

Pacijenti sa HbA1c <7% koji su inicijalno dostigli

HbA1c<6,5% (%)

 Kada nivo HbA1c počne da raste, neophodno je uvesti u terapiju

najmanje još jedan lek za većinu pacijenata
Cook MN et al. Diabet Med 2007; 24:350-8.
Data taken from electronic medical records of patients initiating metformin (n=3362) or a sulphonylurea (SU) (n=3070) from 1998 to 2004 in 290 UK primary care
practices. Patients had HbA1c recorded 0-90 days before and 90-365 days after initiating monotherapy .
ADA/EASD consensus, Diabetes Care 2022.
 Većini pacijenata sa T2D je potrebna primarna prevencija

38 countries
90% DISCOVER 1
N = 16,000
Procenat pacijenata sa T2D
bez KV bolesti:
25 countries
70% systematic N = 4.5 million
literature review2

1. Prospective observational studies in 38 countries.

N=15,992. 45.7% endocrinologists/diabetologists, 33.7% primary care physicians, 14.8% internists.
Africa (Algeria and South Africa); the Americas (Argentina, Brazil, Canada, Colombia, Costa Rica, Mexico and Panama); South-East Asia (India and Indonesia); Europe (Austria, Czech Republic,
Denmark, France, Italy, the Netherlands, Norway, Poland, Russia, Spain, Sweden and Turkey); the Eastern Mediterranean - “Middle East” (Bahrain, Egypt, Jordan, Kuwait, Lebanon, Oman, Saudi Arabia,
Tunisia and United Arab Emirates); and the Western Pacific (Australia, China, Japan, Malaysia, South Korea and Taiwan).
2. Systematic literature review.
N=4,549,481. 25 countries: Australia, Belgium, Brazil, Cameroon, China, France, India, Indonesia, Iraq, Ireland, Italy, Korea, Mexico, Netherlands, Portugal, Qatar, Russian Federation, Saudi Arabia,
Scotland, Spain, Sweden, Switzerland, Thailand, UK and USA.
Abbreviations: T2D, type 2 diabetes

1. DISCOVER: Gomes MB et al. Diabetes Res Clin. Pract. 2019; 151:20-32.

2. Einarson TE et al. Cardiovasc Diabetol. 2018;17:83.
 Izbor AD lekova mora biti individualizovan u skladu sa
karakteristikama pacijenta

CV benefits
HbA1C Effect on Risk of Renal Other adverse
reduction weight hypoglycaemia ASCVD HF benefits effects Cost Administration

Potential GI events
Metformin Neutral Low Neutral Neutral $ Oral
benefit Lactic acidosis

Sulphonylureas Moderate* Neutral* Neutral Moderate $ Oral

SGLT-2 GMIs/UTIs, DKA,

Low Benefit Benefit Benefit $$$ Oral
inhibitors volume depletion

DPP-4 inhibitors Neutral Low Neutral Neutral** Neutral $$$ Oral

GLP-1 receptor Gastrointestinal Oral

Low Benefit*** Neutral Moderate $$$$$
agonists events SC injection

Adapted from American Diabetes Association’s standards of medical care in diabetes 2022 (Draznin B et al. Diabetes Care. 2022;45(Suppl 1):S125-S143)
Insulin High Neutral Neutral Neutral
* Newer generation, especially gliclazide, demonstrated lower risk of hypoglycemia and no increased risk of cardiovascular events compared to older
$$ SC injection
generation; ** Potential risk of heart failure with saxagliptin; *** CV benefit demonstrated with liraglutide, dulaglutide and semaglutide (lixisenatide and exenatide: neutral)
Abreviations. ASCVD, atherosclerotic cardiovascular disease; CV, cardiovascular; DKA, diabetic ketoacidosis; GI, gastrointestinal;
genital mycotic infection; HF, heart failure; SC, subcutaneous; UTI, urinary tract
GMI, - 24 -
 Gliklazid MR – Drugačija SU

Gliclazide MR SU as th. group

HbA1c reduction ↓↓↓↓ ↓↓↓↓
Effect on weight Neutral ↑
Risk of hypoglycaemia Low Moderate
CV ASCVD CV Safety Neutral
benefits HF Neutral Neutral
Renal benefits Benefit Neutral
Other adverse effects
Cost $ $
Administration Oral Oral

Adapted from American Diabetes Association’s standards of medical care in diabetes 2022 (Draznin B et al. Diabetes Care. 2022;45(Suppl 1):S125-S143)
*Newer generation, especially gliclazide, demonstrated lower risk of hypoglycemia and no increased risk of cardiovascular events compared to older generation
 Gliklazid MR u poredjenju sa novim molekulima

HbA1C CV benefits
Effect on Risk of Renal Other adverse
reduction weight hypoglycaemia ASCVD HF benefits effects Cost Administration

Potential GI events
Metformin Neutral Low Neutral Neutral $ Oral
benefit Lactic acidosis

Other Moderate Neutral Neutral Moderate $ Oral

Sulphonylureas
Gliclazide MR Neutral Low CV safety Neutral Benefit $ Oral

SGLT-2 GMIs/UTIs, DKA,

Low Low Benefit Benefit Benefit $$$ Oral
inhibitors volume depletion

DPP-4 inhibitors Neutral Low Neutral Neutral** Neutral $$$ Oral

GLP-1 receptor Gastrointestinal Oral

Low Benefit*** Neutral Moderate $$$$$
agonists
Adapted from American Diabetes Association’s standards of medical care in diabetes 2022 (Draznin B et al. Diabetes Care. 2022;45(Suppl 1):S125-S143) events SC injection
*Newer generation, especially gliclazide, demonstrated lower risk of hypoglycemia and no increased risk of cardiovascular events compared to older generation; ** Potential risk of
heart failure with saxagliptin; *** CV benefit demonstrated with liraglutide, dulaglutide and semaglutide (lixisenatide
- 24 - and exenatide: neutral)
Insulin High Neutral Neutral Neutral $$ SC injection
Abreviations. ASCVD, atherosclerotic cardiovascular disease; CV, cardiovascular; DKA, diabetic ketoacidosis; GI, gastrointestinal;
genital
GMI, mycotic infection; HF, heart failure; SC, subcutaneous; UTI, urinary tract
Mesto gliklazida MR u svakodnevnoj praksi

1. Pacijent sa
neregulisanom
glikemijom na
metforminu1
2. Pacijent sa neregulisanom
glikemijom na kombinaciji
metformin/glimepirid1

3. Novodijagnostikovani
pacijenti sa T2D HbA1c veći za
1,5% od ciljnog2 (met+gliklazid
MR)

1. Trubitsyna N et al. Diabetes Res Clin Pract .doi: 10.1016/j.diabres.2015.11.001.

2. Informacije na slajdu predstavljaju ekspertsko mišljenje NTAE
 Gliklazid MR
Snažna efikasnost
Gliklazid MR - Efikasan u kontroli glikemije i prilagođen svakom
pacijentu
bez obzira na početne vrednosti HbA1c

9-
7-8% 8-9%
10%

Što je veći početni HbA1c, to je kontrola glikemije sa gliklazidom veća

Zoungas S et al. Diabetes Res Clin Pract. 2010, 89: 126 –133
 Gliklazid MR - superiorniji u sniženju HbA1c u poredjenju sa
glimepiridom i SGLT2i

Biguanide metformin
Dipeptidyl peptidase-4 inhibitors
Glucagon-like peptide 1 receptor agonists
Sodium glucose transporter-2 inhibitors
Sulfonylureas
Thiazolidinediones

Model-based meta-analysis used to compare 24 T2D drugs from six drug classes in terms of
glycemic control, weight change, and hypoglycemia risk.
Data from 229 RCT were collated, representing 710 individual treatment arms and a total of
121,914 patients.
Abbreviations: RCT, randomized controlled trial; T2D, type 2 diabetes.
Maloney A et al. Clin Pharmacol Ther. 2019;105(5):1213-1223.
Gliklazid MR – Dugoročna kontrola glikemije ADVANCE

Srednja vrednost
9.0 Standardna HbA1c na kraju
8.5
Intenzivirana studije
Srednji HbA1c (%)
8.0

7.5
7.3%
7.0 Δ 0.67% (95% CI 0.64 - 0.70); p<0.001
6.5%
6.5

6.0 Dugoročna kontrola glikemije tokom 5 godina

0 6 12 18 24 30 36 42 48 54 60 66

Period praćenja (Meseci)

Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. ADVANCE Collaborative Group. N Engl J Med 2008; 358:2560-2572.
 Benefiti od kombinovane terapije dodatkom SGLT2i na SU
All classes of antidiabetic drugs improved glucose control when added to SU.
However, SGLT-2i exhibited superior effects in terms of weight loss and did not increase the risk of hypoglycemia.
Differences versus placebo in efficacy and safety outcomes.

HbA1c (%) Mean with 95% CI FPG (mmol/l) Mean with 95% CI
GLP-1 RA -1.12 (-1.36, -0.89) TZD -2.37 (-2.98, -1.76)
Basal -0.97 (-1.48, -0.46) SGLT-2i -1.84 (-2.40, -1.27)
TZD -0.85 (-1.07, -0.63)
Met -1.79 (-2.52, -1.06)
Met -0.82 (-1.20, -0.44)
GLP-1 RA -1.46 (-2.01, -0.91)
DPP-4i -0.67 (-0.83,-0.51)
SGLT-2i -0.65 (-0.96, -0.35) AGI -0.78 (-1.37,-0.20)
AGI -0.59 (-0.89, -0.29) DPP-4i -0.68 (-0.99, -0.37)

-1.5 -1.2 -0.6 -0.3 0 -3 -2.3 -0.9 -0.2 0

Body weight (kg) Mean with 95% CI Hypoglycemia OR with 95% CI

SGLT-2i -1.00 (-1.73, -0.27) AGI 1.16 (0.55, 2.44)
GLP-1 RA -0.56 (-1.10, -0.02) SGLT-2i 1.35 (0.81, 2.25)
DPP-4i 1.51 (1.05, 2.15)
AGI -0.30 (-0.98, -0.39)
TZD 2.04 (1.25, 3.33)
DPP-4i 1.00 (0.90,1.11)
Met 2.76 (1.55, 4.92)
Met 1.45 (0.47, 2,43) Basal 3.61 (1.48, 8.77)
TZD 1.91 (0.92, 2.91) GLP-1 RA 4.75 (2.61, 8.62)
-1.7 -0.5 0 1.8 2.9 0.5 1
Favours Treatment Favours placebo
4.5 9

Network meta-analyses 10,032 (24 trials), patients with type 2 diabetes

Favours Treatment Favours placebo
Abbreviations: AGI, alpha-glucosidase inhibitors; DPP4i, dipeptidyl peptidase-4 inhibitors; GLP-1RA, glucagon-like peptide-1 receptor
antagonists; 23
Met, metformin;
Qian D et al. PLoSSGLT2i, sodium–glucose linked
One. 2018.27;13(8):e0202563. 1 transporter 2 inhibitors; TZD, thiazolidinediones - 51 -
 Metformin + Sulphonylurea Participants

Benefiti od kombinovane terapije dodatkom SGLT2i na Metformin+ SU

Efikasnost
Hypoglycemia (Odds ratio)

-
-

Systemic review and meta-analysis including 43 RCTs with metformin in combination with SU
TZD
(N=20),
(N=10), basal or rapid acting insulin (N=6), DPP–4i (N=3), GLP–1RA (N=2) and SGLT–2i 24
Zaccardi F et al. Diabetes Obes Metab. 2018.;20(4):985-997
(N=2) N=16590 participants
ŠTA SVE (NE)ZNAMO O
OAD
Prof.dr Aleksandra Jotić, endokrinolog, UKC Srbije
datum: 28.11.2022.
Ovo predavanje je sponzorisano od strane kompanije
Servier d.o.o
 Gliklazid MR
Nizak rizik od hipoglikemija
 Gliclazid MR - nizak rizik od hipoglikemije
Kao i kod novih molekula

Glibenclamide
Glipizide
Comparative risk Glimepiride
of hypoglycemia Nateglinide
Gliclazide
Rosiglitazone
Canagliflozin
Sitagliptin
Saxagliptin
Vildagliptin
Dapagliflozin
Meta-analysis from 27 trials. While six trials reported no criteria for hypoglycemia, Pioglitazone
the remainder used various criteria ranging from symptoms suggestive of
hypoglycemia to symptomatic hypoglyaemia confirmed by a glucose
measurement.
Hypoglycemic episodes requiring third party or medical assistance were
typically classified as severe. 0.01 0.1 1 10 100
Yet, no consistent criteria were applied for minor hypoglycemia.
N= 16,260 patients Log (OR)
Among 1878 placebo and 5572 treated with SU (glibenclamide: 261; gliclazide:
847; glimepiride: 2981; and glipizide: 1483)
Follow-up of 16-52 weeks
Abbreviations: SU, sulfonylurea 28
Gliklazid MR – dokazano bezbedna SU

ACCORD Study Group. N Engl J Med. 2008;358:2545-2559

ADVANCE Group. N Engl JMed 2008; 358:2560-72
CONTROL Group. Diabetologia. 2009, August 6. Epub ahead of print
Aravind et al.Curr Res Med Opin 2012;28(8):1-8.
 Gliklazid MR bezbedna i efikasna SU i tokom posta

BEZBEDNOST I EFIKASNOST TOKOM

POSTA

DIARAMADAN - Prva studija koja je pokazala ,,u

stvarnom okruženju’’ da ljudi sa T2D , koji u terapiji
imaju Diaprel® MR mogu da poste sigurno sa veoma
niskim rizikom od hipoglikemije, a pritom
održavajući glikemijsku kontrolu i telesnu težinu.

Observational, N=1214,
9 countries: India, Indonesia, Malaysia, Bangladesh, Pakistan, Egypt, Saudi Arabia, United Arab
Emirates, Kuwait
Definitions: Symptomatic hypoglycaemia:
Confirmed hypoglycaemia is defined as hypoglycaemia symptomatic or hypoglycaemia asymptomatic
Abbreviations: FPG, fasting plasma glucose
Hassanein M, Al Sifri S, Shaikh S, et al. A real-world study in patients with type 2 diabetes mellitus treated with gliclazide modified-release during fasting: DIA-RAMADAN. Diabetes Res Clin Pract. 2020. doi: https://doi.org/10.1016/j.diabres.2020.108154.
 Metformin + Sulphonylurea

Benefiti od kombinovane terapije dodatkom SGLT2i na Metformin+ SU

Metformin + Sulphonylurea Participants

Nizak rizik od
hipoglikemije

Systemic review and meta-analysis including 43 RCTs with metformin in combination with SU
TZD
(N=20),
(N=10), basal or rapid acting insulin (N=6), DPP–4i (N=3), GLP–1RA (N=2) and SGLT–2i 31
Zaccardi F et al. Diabetes Obes Metab. 2018.;20(4):985-997
(N=2) N=16590 participants
 Gliklazid MR
bez uticaja na TT
 Gliklazid MR -efikasna glikemijska kontrola bez porasta
TT

Pacijenti lečeni lekom

Gliklazid MR u intenzivnoj
grupi nakon 5 godina
nisu imali porast telesne
težine 1

Gliklazid MR 1 2 3

Kod gojaznih pacijenata, koji ne uspevaju da imaju zdrav način

života, terapijska odluka treba da bude u korist antidijabetika
koji ne utiče na povećanje telesne težine
3.VADT Group. N Engl Med.2009;360:129-139 .
2. ACCORD Study Group. N Engl J Med. 2008;358:2545-2559
1. ADVANCE Group. N Engl JMed 2008; 358:2560-72
 Benefiti od kombinovane terapije dodatkom SGLT2i na Metformin+ SU

Metformin + Sulphonylurea Participants

Gubitak težine

Systemic review and meta-analysis including 43 RCTs with metformin in combination with SU
TZD
(N=20),
(N=10), basal or rapid acting insulin (N=6), DPP–4i (N=3), GLP–1RA (N=2) and SGLT–2i 34
Zaccardi F et al. Diabetes Obes Metab. 2018.;20(4):985-997
(N=2) N=16590 participants
 Gliklazid MR
zaštita od komplikacija
Gliklazid MR pokazuje najveću selektivnost za SUR1 receptore

Gribble FM. Diabetologia. 1999;42:845-848.

Gribble FM. Diabetes. 1998;47:1412-1418.

36
Song DK. Br J Pharmacol. 2001;133:193-199.
 Gliklazid MR selektivnim vezivanjem za pankreas čuva srce

Relative risk (95% CI)

Chlorpropamide 1.45 (0.68, 2.44)
Tolbutamide 1.11 (0.79, 1.55)
CV Glibenclamide Reference group
mortality
Glipizide 1.01 (0.72, 1.43)
Glimepiride 0.79 (0.57, 1.11)
Gliclazide 0.60 (0.45, 0.84)
Chlorpropamide 1.34 (0.98, 1.86)
Tolbutamide 1.13 (0.90, 1.42)
Glibenclamide Reference group
All-cause
mortality Glipizide 0.98 (0.80, 1.19)
Glimepiride 0.83 (0.68, 1.00)
Gliclazide 0.65 (0.53, 0.79)

0.25 1 2
4
0.5 Higher risk than glibenclamide
Lower risk than glibenclamide
Meta-analysis of 24 studies reporting the risk of CV and all-cause mortaly with
SUs. N=167,327 type 2 diabetes patients of which:
N=19,334 patients treated by gliclazide; N=49,389 patients treated by glimepiride; N=14,464 patients treated by glipizide;
N=77,169 patients treated by glibenclamide; N=6187 patients treated by tolbutamide; N=784 patients treated by
chlorpropamide
Abbreviations: CV, cardiovascular; SU, sulfonylurea 37
Gliklazid MR – prevencija svih stadijuma bubrežne insuficijencije

Gliclazide MRhas established long-term renal benefits and cardiovascular safety

Renal protection is a key long-term benefit of Gliclazide MR

Figure 1. Patient comorbidities which impacted the current therapy choice with gliclazide1,2

New onset of New or New onset of

micro- worsening macro- ESRD Gliclazide shows a statistically significant
albuminuria nephropathy albuminuria
reduction of 21% of new or worsening
nephropathy.
-9%
(p=0.01)
N= 11,140 with a history of major macrovascular or
microvascular disease or at least 1 other vascular risk factor
-21% Strategy of HbA1c target Treatment
(p<0.001)
Standard glucose control Local guidelines Any SU except gliclazide
-30%
(p=0.06) Intensive glucose control ≤6.5% Gliclazide MR + other OAD

Australia, Canada, China, Czech Republic, Estonia, France, Germany, Hungary,

-65% India, Ireland, Italy, Lithuania, Malaysia, Netherlands, New Zealand, Philippines,
Poland, Russia, Slovakia, UK
(p=0.01)

T2D: Type 2 Diabetes; OAD: oral anti-diabetic drug; ESRD: End stage renal disease

1- Perkovic et al.,Kidney international. 2013 Mar 1;83(3):517-23; 2- ADVANCE collaborative group, New England journal of medicine. 2008 Jun 12;358(24):2560-
72.; 3- Satoh et al,, Diabetes research and clinical practice. 2005 Dec 1;70(3):291-7. .
Posledica reverzibilnog vezivanja na nivou pankreasa...
Gliklazid MR obezbeđuje pravu dozu insulina u pravom trenutku

Glukozno zavisna insulinska sekrecija prema potrebama pacijenta

Gliklazid MR stimuliše beta ćelije po potrebi

Štiti pankreas
od
iscrpljivanja

Gliklazid MR stimuliše oslobađanje insulina sa povećanjem nivoa glikemije i

redukuje oslobađanje insulina sa sniženjem glikemije
Gregorio F et al. Diabetes Res Clin Pract. 1992;18:197-206.
Čuva β-ćeliju i produžava vreme do insulina za 14.5 godina

Gliklazid MR
60mg

5. Satoh J et al. Diabetes Res Clin Pract 2005; 70: 291-297.

Gliklazid MR
Mogućnost titriranja doze do 2 tablete

Zoungas S et al. Diabetes Res Clin Pract. 2010, 89: 126 –133
 Gliklazid MR
primena u svetlu novih molekula
Gliklazid MR, rešenje za pacijente....

...koji ne postižu
ciljne vrednosti
HbA1c na
metforminu

Sažetak karakteristika leka Diaprel MR, Mart 2021.

Lek Diaprel MR je indikovan za insulin nezavisni dijabetes (tip 2) kod odraslih, kada dijeta, fizička aktivnost i smanjenje telesne mase nisu
dovoljni za postizanje zadovoljavajuće kontrole koncentracije glukoze u krvi.
 Benefiti od istovremene primene_ Gliklazid MR +
SGLT2i

“Dobri SNAŽNA KV
partneri” EFIKASNOST ZAŠTITA

Adapted from Qian D et al. PLoS ONE. 2018;13(8):e0202563. https://doi.org/10.1371/journal.pone.0202563

Zoungas S.et al. Diabetes Res Clin Pract 2010; 89: 126-133.
Jia Y et al. Obes Rev. 2018 Sep 17. doi: 10.1111/obr.12753. [Epub ahead of print] Review
McMurray JJV,et al.N Engl J Med 2019;381:1995-2008
 Gliklazid MR + GLP1 RA _Pouzdani partneri i danas i
sutra

KOMPLEMENTARNO DEJSTVO

Qian D et al. PLoS ONE. 2018;13(8):e0202563. https://doi.org/10.1371/journal.pone.0202563

Gliklazid MR _primena u svetlu novih molekula

NE
ZAMENITI
VEĆ
KOMBINOVATI
Poruke za poneti
Gliklazid MR – superiorna metabolička kontrola:
• jednostavno doziranje ujutru, jednom dnevno – optimalni efekat tokom 24h 1,2

• efikasna i dugoročna kontrola glikemije 1

• mogućnost titracije do 2 tablete uz nizak rizik od hipoglikemija i bez dobijanja u TM1,2

Gliklazid MR – jedina SU sa dokazanom kardiorenalnom protekcijom:

• dokazana nefroprotekcija u svim stadijumima hronične bubrežne bolesti 4
• Selektivnim vezivanjem za pankreas čuva srce 5

Gliklazid MR – dobro se kombinuje:

1. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. ADVANCE

• Gliklazid MR i SGLT2 inhibitori – dobri partneri 6 Collaborative Group. N Engl J Med 2008; 358:2560-2572.
2. Sažetak karakteristika leka Diaprel MR, Mart 2021.
3. Trubitsyna N et al. Diabetes Res Clin Pract .doi: 10.1016/j.diabres.2015.11.001.
4.Intensive glucose control improves kidney outcomes in patients with type 2 diabetes. Perkovic V et al.
Kidney Int 2013; 83(3): 517-623.
5. Simpson S, Lancet Diabetes Endocrinol. 2015 Jan;3(1):43-51.
RS-076-DMR-22-PPT 6. Qian D et al. PLoS ONE. 2018;13(8):e0202563. https://doi.org/10.1371/journal.pone.0202563
Pitanja?