Ueda2016 symposium -t2 dm management - lobna el toony

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T2DM Management …..

In search for an ideal anti-diabetic agent

LOBNA F ELTOONY Head Of Internal Medicine Department

Assiut University

Faculty Of Medicine

3

Diabetes is a huge and growing problem, and the costs

to society are high and escalating

382 million people have diabetes

By 2035, this number will rise to 592 million

Ref. IDF atlas 06, 2013

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Complex Physiology Complex Management

Insulin resistance

Years of diabetes

Beta-cell failure

Insulin output

0

100

200

300

–10 –5 0 5 10 15 20 25 30

Rel

ativ

e

-cel

l

func

tion

(%)

At risk for

diabetes

Fasting glucose

50100

200

300

Glu

cose

(m

g/dL

)

Post-meal glucose

Lifestyle InsulinSFU, glitinides, exenatide

Metformin, TZDs, AGIs, DPP4 AGI: alpha glucosidase inhibitorSFU: sulfonylurea

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Microvascular

complications

Myocardial

infarction

HbA1c

14%

Lowering HbA1c reduces the risk of Diabetes complications

37%

1%

Diabetes related

death

Peripheral Vascular

Disease

21%

43%

UKPDS

UKPDS = UK Prospective Diabetes Study; randomized patients received either conventional glucose control (primarily based on diet) or intensive glucose control (sulfonylurea or insulin). aP<0.0001. Stratton IM et al. BMJ. 2000;321:405–412.

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Diabetes management guidelines:

a sense of urgency

HbA1c “... the results of the UKPDS

mandate that treatment of type 2 diabetes include

aggressive efforts to lower blood glucose levels as close to

normal as possible”

“Diabetes must be… diagnosed earlier.

And once diagnosed, all types of

diabetes must then be managed

much more aggressively”

American Diabetes Association1

Canadian Diabetes Association2

1American Diabetes Association. Diabetes Care 2003; 26:S28–S32.

2Canadian Diabetes Association. Can J Diabetes 2003; 27 (Suppl. 2):S1–S152.

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All Anti Diabetic agents are effective

but the Important Question is How this efficacy comes?

12

13

HbA1c=haemoglobin A1c; OAD, oral antidiabetic drugs.Jacob AN, et al. Diabetes Obes Metab. 2007; 9:386–393;Kahn SE, et al. N Engl J Med. 2006; 355: 2427–2443;Wright AD, et al. J Diabetes Complications. 2006; 20: 395–401.

Decreasing HbA1c is associated with increased risks of hypoglycaemia and weight gain

Weight gain &

hypoglycaemia

Body w

eig

ht

HbA1c

Pla

sma

glu

cose

14

Hypoglycaemia

1Briscoe VJ, et al. Clin Diabetes 2006;24:115–21;2Cryer PE. Diabetologia 2002;45:937–48

A major limiting factor to achieve intensive

glycaemic control in people with T2DM1

Hypoglycaemia makes clinicians less likely

to implement glycaemic targets2

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Potential Complications and Effects of Severe Hypoglycemia

15

Plasma glucose level

10

20

30

40

50

60

70

80

90

100

110

1

2

3

4

5

6

mg/dL

mmol/L

1. Landstedt-Hallin L et al. J Intern Med. 1999;246:299–307.

2. Cryer PE. J Clin Invest. 2007;117:868–870.

Arrythmia1 Neuroglycopenia2

Abnormal prolonged

cardiac repolarization —

↑ QTc and QT dispersion

Sudden death

Cognitive impairment

Unusual behavior

Seizure

Coma

Brain death

Underlying endothelial

dysfunction leading to

decreased

vasodilatation may

also contribute to

cardiovascular risk.

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Sitagliptin Improves Glycemic Control In a Glucose-

Dependent Manner By Increasing Concentrations of Active

Incretins1–4

aIncretin hormones GLP-1 and GIP are released by the intestine throughout the day, and their levels increase in response to a meal.

GI = gastrointestinal; GIP = glucose-dependent insulinotropic peptide; GLP-1 = glucagon-like peptide-1; DPP-4 = dipeptidyl peptidase-4; FPG = fasting plasma glucose;

PPG = postprandial plasma glucose.

1. Ahrén B. Curr Diabetes Rep. 2003;3:365–372. 2. Drucker DJ. Diabetes Care. 2003;26:2929–2940. 3. Holst JJ. Diabetes Metab Res Rev. 2002;18:430–441. 4. Adapted with permission

from Drucker D. J Clin Invest. 2007;117:24-32. 5. JANUVIA SPC.

Sitagliptin

(DPP-4 inhibitor)

Ingestion

of food

GlucagonGI tract

Inactive

GLP-1

Insulin

Glucose-

dependent

Pancreatic islet

Inactive

GIP

α-cell

β-cell

Glucose-

dependent

Hepatic

glucose

production

Liver

Glucose

FPG, PPG

DPP-4

Active GLP-1a

Active GIPa

X

Skeletal

muscle

Peripheral

glucose uptake

Adipose

tissue

Sitagliptin and Metformin Target the

Metabolic Defects of Type 2 Diabetes

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1. Aschner P et al. Diabetes Care. 2006;29:2632–2637.

2.,Vardarli I et al. Diabetes. 2014;63:663–674.

3. Abbasi F et al. Diabetes Care. 1998;21:1301–1305.

4. Kirpichnikov D et al. Ann Intern Med. 2002;137:25–33.

5. Zhou G et al. J Clin Invest. 2001;108:1167–1174.

6. Solis-Herrera et al. Diabetes Care. 2013;36:2756–2762.

Beta-Cell Dysfunction

Hepatic Glucose Overproduction (HGO)

Insulin Resistance

Sitagliptin improves

markers of beta-cell

function and increases

insulin synthesis and

release.1,2

Sitagliptin reduces

HGO through

suppression of

glucagon from alpha

cells.6

Metformin decreases

HGO by targeting the

liver to decrease

gluconeogenesis and

glycogenolysis.4

Metformin has insulin-

sensitizing

properties.3–5

(Liver > Muscle)

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin

Monotherapy: Change from Baseline in HbA1c by Baseline HbA1c at Week

18

FAS=full analysis set; FDC=fixed-dose combination.

1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5–9, 2009.

2. Data on file, MSD.

Hb

A1c

LS

Mea

n C

han

ge

fro

m B

ase

lin

e, %

Baseline HbA1c,% <8 ≥8 and <9 ≥9 and <10 ≥10 and <11 ≥11

FAS (Week 18)

P=0.009

P<0.001

P<0.001

Mean HbA1c,% 7.6 8.4 9.5 9.4 10.4 12.2

n=

–1.1

–1.6

–2.0

–2.9–2.7

–2.1

–1.7

–1.1

–0.8

–4.0

–3.5

–3.0

–2.5

–2.0

–1.5

–1.0

–0.5

0

Sitagliptin/metformin FDC

Metformin

99 95 99 11187 101 124 109 150 148

P=0.158

P=0.111

–3.6

HbA1c-Lowering Efficacy of Sitagliptin atWeek 30 Was Non inferior to That of Glimepiridein Patients Inadequately Controlled on Metformin1

LS=least squares; SE=standard error.

aMean dose of glimepiride (following the 18-week titration period) was 2.1 mg per day.

1. Arechavaleta R et al. Diabetes Obes Metab. 2011;13(2):160–168.

Week

LS

Mean

(±

SE

) H

bA

1c, %

Per-Protocol Population

6.0

6.2

6.4

6.6

6.8

7.0

7.2

7.4

7.6

7.8

8.0

0 6 12 18 24 30

(95% CI)

0.07% (–0.03, 0.16)

Sitagliptin 100 mg + metformin (n=443)

Glimepiridea + metformin (n=436)

–0.47

–0.54

Sitagliptin Was Associated With a Lower Incidence of

Hypoglycemia and Reduced Body Weight vs Glimepiride1

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Hypoglycemia Over 30 Weeks Body Weight Change at Week 30

APaT=all patients as treated; CI=confidence interval; LS=least-squares.aMean dose of glimepiride (following the 18-week titration period) was 2.1 mg per day.

1. Arechavaleta R et al. Diabetes Obes Metab. 2011;13:160–168.

2. Data on file, MSD.

Pat

ien

ts W

ith

≥1

Hyp

og

lyce

mic

Ep

iso

de,

%

LS

Mea

n (

95%

CI)

Ch

ang

e in

Bo

dy

Wei

gh

t F

rom

Bas

elin

e, k

g

n=516 n=518

All patients inadequately controlled on metformin monotherapy (≥1500 mg/day)

(APaT Population)

(95% CI)

–15.0% (–19.3, –10.9) (P<0.001)

Sitagliptin 100 mg + metformin

Glimepiridea + metformin

= –2.0 kg

(P<0.001)

n=461

n=465

ODYSSÉE: HbA1c Over Time Until

Modification of Combination Therapy1

Sitagliptin + metformin SU + metforminLS=least square; SD=standard deviation; SU=sulfonylurea.

1. Valensi P et al. American Diabetes Association 2014. Abstract 136-LB.

6.4

6.6

6.8

7.0

7.2

7.4

7.6

7.8

Inclusion 6 12 18 24 30 36

LS M

ean

HbA

1c±

SD

, %

n=1735

n=678

n=1,263

n=490

n=1,089

n=370

n=921

n=286

n=793

n=245

n=688

n=206

n=592

n=190

LS Mean Change in HbA1c:

~ –0.6 in both groups

7.7

7.5

7.3

7.1

6.9

6.7

6.5

Time, months

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Gliclazide was the most

commonly prescribed SU (54%)

ODYSSÉE: Patient-reported Hypoglycemia

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aDifference between baseline weight was statistically significant: sitaglptin + metformin, 85.0 kg; SU + metformin, 83.4 kg, P=0.002)

SU=sulfonylurea.

1. Valensi P et al. American Diabetes Association 2014. Abstract 136-LB.

100

30

20

10

0

9.7%

21%

Pat

ien

t s

Wit

h ≥

1 E

pis

od

e o

f H

ypo

gly

cem

ia, %

Sitagliptin + metformin (n=1,874) SU + metformin (n=733)

Patient-reported

Hypoglycemia

During Study

Follow-Up or Until

Change in

Therapy

Gliclazide was the most

commonly prescribed SU (54%)

Durability 29

Sitagliptin and -cell mass

Mu J. et al. Eur J Pharm 2009; 623: 148-154

Sitagliptin Add-on to Metformin – 30-week study

Adding Sitagliptin 100 mg Once Daily to Metformin Improved Markers of β-cell Function at 18 Weeks

HOMA-β=homeostasis model of assessment β; LSM=least squares mean.aSitagliptin=100 mg/day; bMetformin≥1500 mg/day.

Raz I et al. Curr Med Res Opin. 2008;24:537–550.

LS

M C

han

ge in

Pro

insu

lin

to

In

su

lin

Rati

o F

rom

Base

lin

e

Proinsulin to Insulin Ratio

P<0.001

17.0

2.5

–5

0

5

10

15

20

LS

M C

han

ge in

HO

MA

-β

Fro

m B

ase

lin

e, %

Sitagliptina + metforminb Placebo + metforminb

HOMA-β

P<0.001

–0.12

–0.03

–0.20

–0.15

–0.10

–0.05

0.00

0.05

n=74 n=65

n=72 n=60

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P.Valensi et al. Treatment Maintenance Duration of Dual Therapy with Metformin and Sitagliptin in Type 2 Diabetes: The Odyssee

Observational Study. Diabetes 63(S1): LB-35 Abst 136-LB 2014 Jun 13-17 2014 - ADA 2014 74th American Diabetes Association

Scientific Sessions, San Francisco, California Abst: 136-LB

ODYSSÉE Study: Results…

Treatment maintenance duration until treatment modification

MetSita group : 43.2 months [95%CI: 41.4 – NE*]

MetSU group : 20.2 months [95%CI: 17.0 - 25.1]

Pro

po

rtio

n o

f P

ati

en

ts m

ain

tain

ed

*non-evaluable

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The natural course of HbA1c

Ferrannini et al. J Clin Endocrinol Metab 2005

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TECOS CV Safety Trial:

Time-to-Initiation of Insulin Therapy1

Intention-to-Treat Populationa

Sitagliptin

N=5,608

Placebo

N=5,655 HR (95% CI) P-value

Initiation of insulin ,

n (%); rate per 100 patient-years

542 (9.7)

3.44

744 (13.2);

4.850.70 (0.63, 0.79) <0.001

Intention-to-Treat Populationa Sitagliptin Placebo

Cumulative incidence of events, % (95% CI) N=5,608 N=5,655

1 year 3.2 (2.77, 3.72) 4.8 (4.29, 5.43)

2 years 6.4 (5.75, 7.07) 9.7 (8.93, 10.53)

3 years 9.8 (8.96, 10.71) 14.1 (13.09, 15.12)

4 years 13.2 (12.09, 14.50) 17.5 (16.27, 18.89)

aIn patients not receiving insulin at baseline

TECOS = Trial Evaluating Cardiovascular Outcomes With Sitagliptin; CV = cardiovascular; HR = hazard ratio; CI = confidence interval.

1. Green JB et al. [published online ahead of print June 8, 2015] N Engl J Med. doi: 10.1056/NEJMoa1501352.

30%

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June 2015

Inzucchi et al published online: 22 JUN 2015Diabetes, Obesity and Metabolism 2015

Study Overview…

This study provides insight about different oral treatment regimens

and their possible effect on initiation of insulin under real-world

conditions.

Real-world research is an important complement to clinical trials as

we seek to improve patient health outcomes.

The objectives of the study were to assess:

• The differences in time to initiation of insulin use.

• The proportion of the population initiating insulin among patients

taking the combination of JANUVIA and metformin, and patients

taking the combination of a sulfonylurea and metformin.Inzucchi et al published online: 22 JUN 2015Diabetes, Obesity and Metabolism 2015

This Observational retrospective cohort study

used a propensity score matched sample from the

GE Centricity Electronic Medical Record database,

initially including 7,728 patients with type 2

diabetes who used JANUVIA (n=3,864) or a

sulfonylurea (n=3,864) as dual therapy with

metformin for (for Six Years) in 2006 to 2013.


Results…

Results from a late-breaking observational study showed that patients with type 2 diabetes treated

with JANUVIA progressed more slowly to insulin than patients taking a sulfonylurea

(p=0.0034).

This Analysis indicated that at year six, patients in the JANUVIA group were 24 percent

less likely to initiate insulin during the period of observation compared to patients taking a

sulfonylurea (p=0.0011).Inzucchi et al published online: 22 JUN 2015Diabetes, Obesity and Metabolism 2015

Conclusions: In this real-world matched

cohort study, patients with T2DM treated with

sitagliptin had a significantly lower risk of

insulin initiation compared with patients

treated with sulphonylurea, both as add-on to

metformin.

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Why Sitagliptin? Uniqueness

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Sitagliptin

Molecular structure

Half Life (T1/2) 12.4 hrs

DPP-4 Inhibition* post 24 hrs 100mg QD 80-97% @ 24hrs

DPP-4 Peak Inhibition ~97%

Selectivity for DPP-IV vs. DPP-8/DPP-9*2600 fold for DPP4 vs. DPP-8

10,000 fold for DPP4 vs. DPP-9

Selectivity High

Metabolism ~16% metabolized

Bioavailability ~87%

Liver Monitoring NO

Elimination

Kidney (87%)

79% mostly unchanged

Liver (13%)

FDA YES

* All use different proprietary assays with different dilutions and therefore % DPP-4 inhibition cannot be compared across assays

Data on file, MSD

F

F

F ON

NH2

N NN

CF3

Why Sitagliptin? Safety Profile

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In search for an Ideal anti diabetic

medication

There is a strong clinical need to find glucose lowering agent that are , at a

minimum , safe ………

Meglitinide

Sulfonylureas

Hypoglycemia

Biguanides

α-Glucosidaseinhibitors

GI disturbance

Sulfonylureas

Meglitinides

Thiazolidinediones

Weight gain

Major Concerns

with Hypoglycemic Agents

Glycemic Variability

Cardiovascular safety of OADs?

Ischemic preconditioning and

sulfonylureas

GLP-1 Actions on the Heart:

Direct or Indirect?

Ussher J, Drucker DJ, Endocrine Rev. 2012 Apr;33(2):187-215.

1. Golden SH. Am J Cardiol 2011;108 (Suppl):59B-67B2. Fonseca V. Am J Cardiol 2011;108 (supp):52B–58Bl

3. Clinicaltrials.gov

Therapies N Population Endpoints Results

TECOS Sitagliptin/ Placebo

14,000 Established CVD CV death, NF MI or CVA, unstableangina hospital.

Dec 2014

SAVOR-TIMI 53 Saxagliptin/ Placebo

16,5003 CVD or ≥ 2 RF CV death, NF MI or ischemicstroke

June 2014

CAROLINA Linagliptin/ Glimepiride

6000 CVD or ≥ 2 RF CV death, NF MI or CVA, unstableangina hospital.

Sept 2018

LEADER Liraglutide/ Placebo

8754 CVD, PAD, CKD, CHF or RF if >60yrs

CV death, NF MI or stroke, revasc

Jan 2016

EXSCEL Exenatide LAR/Placebo

9500 Not specified CV death, NF MI or stroke

Mar 2017

Ongoing Cardiovascular Outcome Trials:DPP-4 Inhibitors and GLP-1 Agonists

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TECOS CV Safety Trial:Trial Evaluating Cardiovascular Outcomes With Sitagliptin

To assess the long-term CV safety of adding sitagliptin to

usual care, as compared with usual care alone, in patients

with type 2 diabetes and established CV disease

TECOS = Trial Evaluating Cardiovascular Outcomes With Sitagliptin; CV = cardiovascular.


Usual care defined as care provided by patient’s physicians based on local and

institutional practice and regional guidelines, and included continuation of existing

therapy at baseline and adjustment of open-label therapy as required during study

Primary Objective1

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Primary OutcomePrimary outcomea was time from randomization to the first confirmedb:

CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization

Secondary Outcomes Other Prespecified Outcomes

Composite end point of: time to first

adjudicated, confirmed CV-related

death, nonfatal MI, or nonfatal stroke

Time to the occurrence of the individual

components of the primary end point

Time to all-cause mortality

Time to hospital admission for

adjudicated congestive heart failure

Changes from baseline in urinary

albumin:creatinine ratio, eGFR, HbA1c, body weight

Time to initiation of additional antihyperglycemic

therapy and/or initiation of chronic insulin

Time to non-CV death; time to first CV or peripheral

revascularization procedure; frequency of severe

hypoglycemia

Counts of outpatient visits and hospitalizations

aIf both MACE+ and MACE analyses met noninferiority and HR <1.0, superiority was to be tested.bCV events were adjudicated by an independent committee, blinded to study therapy.

TECOS = Trial Evaluating Cardiovascular Outcomes With Sitagliptin; CV = cardiovascular; MI = myocardial infarction; eGFR = estimated glomerular filtration rate.

1. Green JB et al. Am Heart J. 2013;166:983–989.e7.


Primary and Secondary Outcomes1

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TECOS CV Safety Trial: Primary Composite CV

Outcome (Analysis for non Inferiority)1

aNoninferiority P-value for a margin of 1.30 in hazard ratio.

TECOS = Trial Evaluating Cardiovascular Outcomes With Sitagliptin; CV = cardiovascular; ITT = intention-to-treat; PP = per protocol; HR = hazard ratio; CI = confidence interval.


100

80

60

40

20

0

0 4 8 12 18 24 30 36 42 48

484 8 12 18 24 30 36 420

0

15

Month

Pat

ien

ts w

ith

Eve

nt,

%

No. at Risk

Sitagliptin 7257 6857 6519 6275 5931 5616 3919 2896 1748 1028

Placebo 7266 6846 6449 6165 5803 5421 3780 2743 1690 1005

10

5

Placebo

Sitagliptin

Primary Composite CV Outcome: Per-Protocol Population

HR (95% CI) 0.98 (0.88, 1.09)

P value for non inferiority: P >0.001

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TECOS CV Safety Trial: Hospitalizations for Heart

Failure (ITT)1

TECOS = Trial Evaluating Cardiovascular Outcomes With Sitagliptin; CV = cardiovascular; HR = hazard ratio; CI = confidence interval; ITT = intention-to-treat.


Placebo

229 (3.1%)

Sitagliptin

228 (3.1%)

Hospitalizations for Heart Failure: Intention-to-Treat Population

100

80

60

40

20

0

0 4 8 12 18 24 30 36 42 48

484 8 12 18 24 30 36 420

0

1

2

3

4

5

Month

Pat

ien

ts w

ith

Eve

nt

(%)

No. at Risk

Sitagliptin 7332 7189 7036 6917 6780 6619 4728 3515 2175 1324

Placebo 7339 7204 7025 6903 6712 6549 4599 3443 2131 1315

HR (95% CI) 1.00 (0.83, 1.20)

Between group difference was not statistically significant (P=0.98)

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Non-CV outcomesa Sitagliptin Placebo

n (%); rate per 100 patient-years N=7,332 N=7,339 HR (95% CI) P-value

Acute pancreatitis 23 (0.3);

0.11

12 (0.2);

0.06

1.93 (0.96, 3.88) 0.07

Charter-defined cancer 268 (3.7);

1.25

290 (4.0);

1.37

0.91 (0.77, 1.08) 0.27

Pancreatic cancer 9 (0.1);

0.04

14 (0.2);

0.07

0.66 (0.28, 1.51) 0.32

Severe hypoglycemia 160 (2.2);

0.78

143 (1.9);

0.70

1.12 (0.89, 1.40) 0.33


Key Non-CV Outcomes (ITT)1

aITT population.

TECOS = Trial Evaluating Cardiovascular Outcomes With Sitagliptin; CV = cardiovascular; ITT = intention-to-treat; HR = hazard ratio; CI = confidence interval.


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TECOS CV Safety Trial: Summary of Results1

Sitagliptin met primary end point (no increased CV risk) when added to

usual care in patients with type 2 diabetes and established CV disease

Sitagliptin therapy did not increase all-cause mortality, CV death, or

non-CV death

No between-group difference in hospitalization for heart failure

Sitagliptin treatment not associated with a significant increase in severe

hypoglycemia

TECOS = Trial Evaluating Cardiovascular Outcomes With Sitagliptin; CV = cardiovascular.


Healthy eating, weight control, increased physical activity & diabetes education

Metformin high low risk

neutral/loss

GI / lactic acidosis

low

If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin +

Metformin +

Metformin +

Metformin +

Metformin +

high low risk

gain

edema, HF, fxs

low

Thiazolidine- dione

intermediate low risk

neutral

rare

high

DPP-4 inhibitor

highest high risk

gain

hypoglycemia

variable

Insulin (basal)

Metformin +

Metformin +

Metformin +

Metformin +

Metformin +

Basal Insulin +

Sulfonylurea

+

TZD

DPP-4-i

GLP-1-RA

Insulin§

or

or

or

or

Thiazolidine-dione

+ SU

DPP-4-i

GLP-1-RA

Insulin§

TZD

DPP-4-i

or

or

or

GLP-1-RA

high low risk

loss

GI

high

GLP-1 receptor agonist

Sulfonylurea

high moderate risk

gain

hypoglycemia

low

SGLT2 inhibitor

intermediate low risk

loss

GU, dehydration

high

SU

TZD

Insulin§

GLP-1 receptor agonist

+

SGLT-2 Inhibitor +

SU

TZD

Insulin§

Metformin +

Metformin +

or

or

or

or

SGLT2-i

or

or

or

SGLT2-i

Mono- therapy

Efficacy* Hypo risk

Weight

Side effects

Costs

Dual therapy†

Efficacy* Hypo risk

Weight

Side effects

Costs

Triple therapy

or

or

DPP-4 Inhibitor

+ SU

TZD

Insulin§

SGLT2-i

or

or

or

SGLT2-i

or

DPP-4-i

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors):

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Metformin +

Combination injectable therapy‡

GLP-1-RA Mealtime Insulin

Insulin (basal)

+

Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0

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Take home message :

DPP4I Sitagliptin Improves Glycemic Control In a Glucose-

Dependent Manner helping T2DM patients to reach targets without

compromise

Sitagliptin and Metformin combination targets the 3 Metabolic

Defects of Type 2 Diabetes with a reduction in A1c up to -3.6%

Because people with type 2 diabetes are at increased risk for CV

complications, understanding the CV safety of these medicines is

important, That is what the TECOS CV Safety Trial addressed – the

CV safety of Sitagliptin

When considering managing T2DM with CV disease ; Sitagliptin

should be on top of the list.

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Thank You ….

Ueda2016 symposium -t2 dm management - lobna el toony

Health & Medicine

Transcript of Ueda2016 symposium -t2 dm management - lobna el toony