Đái tháo đường týp 2:

Những tiến bộ mới

trong Quản lý và Thực hành lâm sàng

PGS.TS Nguyễn Thị Bích Đào

Những thách thức

• Chi phí chăm sóc ĐTĐ ngày càng tăng

• Biến chứng còn nhiều

• Chất lượng cuộc sống: bị hạn chế

• Chăm sóc, theo dõi giữa các lần khám trực tiếp: còn

khoảng cách

• Bệnh nhân ở vùng xa, khó tiếp cận thường xuyên

HbA1c không phản ánh

mức độ biến thiên đường huyết

Adv Ther (2019) 36:579–596 https://doi.org/10.1007/s12325-019-0870-x

Những vấn đề đương đại

trong lĩnh vực đái tháo đường Chăm sóc Đái tháo đường đang thay đổi nhanh chóng

Quản lý

Công nghệ

Các nghiên cứu

Phương pháp điều trị mới

Diabetes Technology

Thuật ngữ được sử dụng để mô tả

Phần cứng,

Thiết bị

Phần mềm

Sử dụng để giúp kiểm soát glucose máu

Cải thiện sự chăm sóc với Telemedicin

Telemedicine trong nhãn khoa giúp sàng

lọc DR

Diabetes Technology -Tiêu chuẩn chăm sóc y

tế trong Đái tháo đường ADA 2019

Trong lịch sử, Diabetes Technology được chia thành hai

loại chính:

• Thiết bị sử dụng Insulin: ống tiêm, bút hoặc bơm

• Theo dõi đường huyết

máy đo đường huyết hoặc máy đo đường huyết liên tục.

• máy đo đường huyết liên tục

thời gian thực và được quét liên tục

• Thiết bị phân phối insulin tự động.

• International Consensus on

Time-in-Range Outlines

CGM-Based Targets

• The key takeaways were that

people with type 1 and type 2

diabetes should aim to

spend:

• At least 70% of TIR (70-180

mg/dl)

• Less than 25% of time above

180 mg/dl

• Less than 5% of time below

70 mg/dl

Technologies for Diabetes

Management 2019-2029: digital health / digital therapeutics,

side effect management and diagnosis

TỪ NGHÊN CỨU THỬ NGHIỆM LÂM SÀNG

Study MACE* CV death MI Stroke Any Death HHF Renal Outcome

DP

P-4

i

SAVOR-TIMI (Saxagliptin)

EXAMINE (Alogliptin)

TECOS (Sitagliptin)

CARMELINA

(Linagliptin)

SGLT

2i

EMPA-REG

OUTCOME

(Empagliflozin)

CANVAS

(Canagliflozin)

DECLARE (Dapagliflozin)

GLP

-1

ELIXA

(Lixisenatide)

LEADER (Liraglutide)

SUSTAIN-6

(Semaglutide)

EXSCEL (Exenatide)

* All studies use 3P-MACE (CV death, MI, stroke) except TECOS and ELIXA which adds hospitalization for

unstable angina

** p>0.05 for individual components of fatal, nonfatal and silent MI, p = 0.046 for composite of fatal, nonfatal

and silent MI

Overall picture of recent CVOTs:

Trial

SGLT2i Placebo

HR (95%

CI) p-value

n event/

N analysed

(%)

Rate/

1000

PY

n event/

N analysed

(%)

Rate/

1000

PY

Dedicated cardiovascular outcomes trials: exploratory analyses

EMPA-REG OUTCOME1

Doubling of serum

creatinine,* RRT or death

from kidney causes

81/4645 6.3 71/2323 11.5 0.54 (0.40,

0.75) <0.001†

DECLARE-TIMI 582

≥40% decrease in eGFR to

<60 ml/min/1.73 m2, new

ESRD or death from kidney

causes

127/8582 3.7 238/8578 7.0 0.53 (0.43,

0.66) NR

CANVAS Program3

Doubling of serum

creatinine, ESKD or death

from kidney causes

NR 1.5 NR 2.8 0.53 (0.33,

0.84) NR

Dedicated kidney outcomes trial: primary analysis

CREDENCE4

Doubling of serum

creatinine, ESKD or death

from kidney causes

153/2202 27.0 224/2199 40.4 0.66 (0.53,

0.81) <0.001

Kidney outcomes in SGLT2 inhibitor outcomes

trials

44

0.25 0.5 1 2

Favours SGLT2i Favours placebo Comparisons of trials should be interpreted with caution due to differences in study design, populations and

methodology

*Accompanied by eGFR ≤45 ml/min/1.73 m2; †Nominal p-value. eGFR, estimated glomerular filtration rate; ESKD, end-

stage kidney disease; ESRD, end-stage renal disease; NR, not reported; PY, patient-years; RRT, renal replacement

therapy; SGLT2i, sodium-glucose co-transporter-2 inhibitor

1. Wanner C et al. N Engl J Med 2016;375:323; 2. Wiviott SD et al. N Engl J Med 2019;380:347; 3. Perkovic V et al.

Lancet Diabetes Endocrinol 2018;6:691;

4. Perkovic V et al. N Engl J Med 2019; doi: 10.1056/NEJMoa1811744

CREDENCE

EMPA-REG OUTCOME®: Overall trial

population

Secondary Composite Kidney Outcomes in

EMPA-REG OUTCOME® and CREDENCE

14

0

5

10

15

20

25

0 26 52 78 104 130 156 182Months since randomization

HR 0.66

(95% CI, 0.53, 0.81)

p<0.001

6 1

2 1

8

2

4

30 3

6

4

2

Pa

rtic

ipa

nts

wit

h a

n e

ve

nt

(%)

Placebo

Canagliflozin

Placebo

Empagliflozin

HR 0.54

(95% CI 0.40, 0.75)

p<0.001

8

7

6

5

4

3

2

1

0

0 6 12 18 24 30 36 42 48

Months

Composite of ESKD, doubling of

serum

creatinine or death from kidney

causes

Composite of renal replacement

therapy, doubling of serum creatinine

or death from kidney causes Comparison of trials should be interpreted with caution due to differences in study design, populations

and methodology

Perkovic V et al. N Engl J Med 2019;DOI:10.1056/NEJMoa1811744; Wanner C et al. N Engl J Med 2016;375:323

0.25 1 4

Comparator Placebo Hazard ratio (95% CI)

Hazard ratio (95% CI) n with event/N analysed

ESKD, sustained doubling of serum creatinine and renal or CV death

EMPA-REG OUTCOME® CREDENCE-like1 49/420 48/221 0.46 (0.31, 0.68)

CREDENCE2 245/2202 340/2199 0.70 (0.59, 0.82)

HHF or CV death

EMPA-REG OUTCOME® CREDENCE-like1 57/422 46/221 0.56 (0.38, 0.83)

CREDENCE2 179/2202 253/2199 0.69 (0.57, 0.83)

CV death

EMPA-REG OUTCOME® CREDENCE-like1 36/422 34/221 0.51 (0.32, 0.82)

CREDENCE2 110/2202 140/2199 0.78 (0.61, 1.00)

ESKD, sustained doubling of serum creatinine and renal death

EMPA-REG OUTCOME® CREDENCE-like1 14/418 17/221 0.38 (0.18, 0.77)

CREDENCE2 153/2202 224/2199 0.66 (0.53, 0.81)

Cardiorenal outcomes in patients with proteinuric DKD

in EMPA-REG OUTCOME® and CREDENCE

15

Favours comparator Favours placebo

Comparison of trials should be interpreted with caution due to differences in study design,

populations and methodology

Cox regression analysis in patients treated with ≥1 dose of study drug. p-value relates to test of

homogeneity of treatment group differences among subgroups (test for treatment by subgroup

interaction), with no adjustment for multiple testing. Data for patients who did not have an event

were censored on the last day they were known to be free of the outcome. „CREDENCE-like‟

definition: eGFR ≥30 to <90 ml/min/1.73 m2 and UACR >300 mg/g. ESKD defined as initiation of

RRT or sustained eGFR <15 ml/min/1.73 m2. eGFR according to CKD-EPI. See slide notes for

abbreviations

1. Wanner C et al. ISN World Congress of Nephrology 2019; poster; 2. Perkovic V et al. N Engl J

Med 2019;DOI:10.1056/NEJMoa1811744

CARMELINA® and CAROLINA® constitute a unique and comprehensive

CVOT programme demonstrating linagliptin‟s long-term safety profile

1. Rosenstock J et al. Cardiovasc Diabetol 2018;17:39; 2. Marx N et al. Diab Vasc Dis Res 2015;12:164

16

N=6979

CARMELINA®1

PLACEBO

controlled

Patients with

established CVD

and/or CKD

2.2 years

duration N=6033

CAROLINA®2

Unique ACTIVE

comparator

(glimepiride)

Patients with early

T2D at increased CV

risk

6.3 years duration

A robust CVOT programme

demonstrating the LONG-TERM

SAFETY OF LINAGLIPTIN

in two independent CVOTs

for a BROAD RANGE of T2D patients

4 of

10

Home Summary in Context

Metabolic/Hypoglycae

mia Cardiovascular Safety Trial Excellence

Continuum of risk for complications in type 2 diabetes

CVD, cardiovascular disease; HbA1c, glycated hemoglobin

1. Rosenstock J et al. JAMA 2019;321:69

CAROLINA® (N=6033)

Comparator Active (sulfonylurea)

Established CVD 42% of patients

Baseline HbA1c 7.2%

Macroalbuminuria

4.3%

Duration of diabetes

6.3 years

Baseline insulin use

0% of patients

Study duration 6.3 years

CARMELINA® (N=6979)1

Comparator Placebo

Established CVD 57% of patients

Baseline HbA1c 8.0%

Macroalbuminuria

38.5%

Duration of diabetes

14.8 years

Baseline insulin use

57% of patients

Study duration 2.2 years

Atherosclerosis

Chronic kidney

disease

Target-organ

damage

Ris

k

Early

disease

Advanced

disease

Asymptoma

tic

Symptomati

c

TỪ NGHÊN CỨU THỬ NGHIỆM LÂM SÀNG

ĐẾN HƯỚNG DẪN THỰC HÀNH LÂM SÀNG

“Among patients with

ASCVD at high risk of

heart failure or in whom

heart failure coexists,

SGLT2 inhibitors are

preferred. For patients with

T2D and CKD, consider

use of a SGLT2 inhibitor

or GLP-1 RA shown to

reduce risk of CKD

progression, CV events,

or both”4

*For SGLT2 inhibitors, evidence modestly stronger for empagliflozin > canagliflozin; for GLP-1 RAs, strongest evidence for

liraglutide > semaglutide > exenatide extended release

ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; GLP-1 RA, glucagon-like peptide-1 receptor

agonist; SGLT2, sodium-glucose co-transporter-2

1. American Diabetes Association. Diabetes Care 2016;39:S1; 2. American Diabetes Association. Diabetes Care 2017;40:S1;

3. American Diabetes Association. Diabetes Care 2018;41:S1; 4. American Diabetes Association. Diabetes Care 2019;42:S1

Thay đổi trong tiếp cận điều trị ĐTĐ từ KSĐH sang quản lý nguy cơ tim mạch

Thay đổi trong tiêu chuẩn chăm sóc ĐTĐ của

Hội ĐTĐ Hoa Kỳ từ 2016−2019

Jan 2016 Jan 2017 Jan 2019

“SGLT2 inhibitors

provide insulin-

independent

glucose lowering…

These agents provide

modest weight loss

and blood pressure

reduction”1

Glucose lowering

“…empagliflozin or

liraglutide should be

considered as they

have been shown to

reduce CV and all-

cause mortality when

added to standard

care”2

Consider

empagliflozin

or liraglutide to reduce

mortality (Level B)

SGLT2 inhibitors or

GLP-1 RAs with

demonstrated CVD

benefit are

recommended* (Level

A) “…incorporate an

agent proven to

reduce major adverse

CV events and

CV mortality (currently

empagliflozin and

liraglutide)”3

Incorporate an agent

proven to reduce CV

events and mortality

(Level A)

Jan 2018

1

ADA 2019: Chu trình điều trị BN ĐTĐ típ 2 - tiếp cận lấy

bệnh nhân làm trung tâm

ADA 2019:

https://doi.org/10.2337/dc19-SINT01

RPA

ADA 2019:

Chiến lược

Tiếp cận điều trị -

Lựa chọn thuốc

BN ĐTĐ typ 2 kèm bệnh tim

mạch do xơ vữa: Ưu tiên

SGLT2i, hoặc GLP1RA đã

chứng minh lợi ích tim mạch

được khuyến cáo là 1 phần

của chiến lược điều trị hạ ĐH

(Mức độ bằng chứng: A)

Mức độ ưu tiên dựa trên kết

quả giảm biến cố tim mạch, tử

vong tim mạch/

tử vong chung

ASCVD, atherosclerotic CVD; CV, cardiovascular; CVD, CV disease; CVOT, CV outcomes trial; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HF, heart failure; SGLT2i,

sodium–glucose transporter 2 inhibitor; T2D, type 2 diabetes.

1. Arnett et al. J Am Coll Cardiol 2019;doi:10.1016/j.jacc.2019.03.010. 2. Das et al. J Am Coll Cardiol 2018;72:3200–23.

Considering CVOTs in clinical practice: what do

cardiology guidelines say?

Recommendation: SGLT2i or GLP-1

RA as an early add-on to metformin in

patients with T2D and CV risk factors

for primary prevention of CVD1

What data are highlighted: CVOT

evidence for primary prevention of

HF with SGLT2i

3 RCTs have shown a significant

reduction in ASCVD events and HF with

use of an SGLT2 inhibitor. Although

most patients studied had established

CVD at baseline, the reduction in HF

has been shown to extend to primary

prevention populations. “

Primary Prevention of HF:

class effect

New AHA–ACC Guidelines1

Secondary Prevention of

CVD: empagliflozin is the

preferred SGLT2i New ACC Consensus

Pathway2 Recommendations

• Patients newly diagnosed

with T2D should discuss

addition of an SGLT2i or

GLP-1 RA with

demonstrated CV benefit,

concurrent to metformin,

lifestyle and CVD therapy

• Empagliflozin is the

preferred SGLT2 inhibitor,

and liraglutide is the

preferred GLP-1 RA

Tóm tắt tác động các thuốc ĐTĐ

lên kết cục tim mạch

European Heart Journal (2019) 00, 1-69

Phác đồ điều

trị ở BN ĐTĐ

típ 2 có bệnh

tim mạch xơ

vữa hoặc

nguy cơ tim

mạch cao/rất

cao

European Heart Journal (2019) 00, 1-69

Addressing the systemic effects of T2D should be

a core objective of patient management Although glucose control has traditionally been the

main focus of diabetes treatment, patients with T2D

require a more holistic clinical management

strategy to address cardio–kidney–metabolic

challenges

Patient-centred care across disciplines should be

implemented using evidence-based guidelines to

improve patient outcomes, quality of life and survival

CVOT evidence demonstrating the clinical benefits of

SGLT2 inhibitors has led to new recommendations

for the management of patients with T2D1–5

CVOT, cardiovascular outcomes trial; SGLT2, sodium-glucose co-transporter-2

1. International Diabetes Federation. Clinical practice recommendations for managing type 2 diabetes in primary care.

2017. https://idf.org/ (accessed Mar 2019); 2. Davies MJ et al. Diabetes Care 2018;41:2669; 3. American Diabetes

Association. Diabetes Care 2019;42:S1; 4. Das SR et al. J Am Coll Cardiol 2018;72:3200; 5. Sarafidis P et al. Nephrol

Dial Transplant 2019;34:208 37

Kết luận

Tiếp cận điều trị ĐTĐ típ 2 thay đổi theo thời gian

1. American Diabetes Association. Diabetes Care 2017;40(Suppl.1):S1-S2;doi:10.2337/dc17-S001. 2. Kirby Br J Diabetes Vasc Dis 2012;12:315–20.

Các chiến lược điều trị cho BN ĐTĐ típ 2

đã được cải thiện đáng kể

Trân trọng cảm ơn sự quan tâm theo dõi

của quí đồng nghiệp