Swiss recommendations 2016Swiss Society of Endocrinology and Diabetology

2. eGFR < 30

ml/min?

DPP-4

Inhibitors

Basal

Insulin

3. Cardiovascular Disease?

yes no

Metformin+

SGLT2 I.

Metformin+

GLP-1 RA

Metformin +

DPP-4 I.

Metformin+

SGLT2 I. Metformin+

GLP-1 RA

+ DPP-4 I. or

Gliclazide or

Basal Insulin

+ Gliclazide or

Basal Insulin

+ Gliclazide

or Basal

Insulin

4. Heart Failure?

Metformin+

SGLT2 I.

+ DPP-4 I.

Basal

Insulin

www.sgedssed.ch

1. Insulin

Deficiency?Basal Insulin

Premixed-InsulinBasal

Bolusor

or

or

Basal Insulin +

GLP-1 RA (Xultophy®)

Guidelines for Type 2 Diabetes:

Keeping the Finger on the Pulse

Lancet Diabetes Endocrinol 2017

Anthony H Barnett, Paul O’Hare, Julian HalcoxPublished Online

April 19, 2017 http://dx.doi.org/10.1016/ S2213-8587(17)30136-5

........Several national guidelines, including those

from Canada and Switzerland, have also

responded quickly to these new data. However, to

our knowledge, NICE in the UK has not yet

responded to this evidence, even though results

from EMPA- REG OUTCOME were published 3

months before the most recent NICE guidance in 2015 (NG28).........

Overview of current T2D treatmentsWhich Priorities?

– Rarely used medications not used in treatment recommendations

(<5% market share = a-glucosidase inhibitors, Pioglitazone, Repaglinide)

– Priority according to treatment strategy

Class

Reduction

cardiovascular

complications

Relative HbA1c

Lowering

(Effectiveness)

Reduced

e-GFR

( <45/<30 mlmin)

Hypo-

glycemia

Risk

Body

WeightApplication Costs

Metformin (long-term) + /- oral $

SGLT-2

Inhibitors - + /- oral $$

GLP-1 R

Agonists () + /- Injection $$$

DPP-4

Inhibitors + /+ oral $$

Insulin

(basal) + /+ Injection

$ -

$$Sulfonyl-

urea -/- oral $

Swiss Recommendations 2016

– Priority: Reduction of cardiovascular disease

www.sgedssed.ch

Classes

Reduction

cardiovascular

complications

Relative HbA1c

Lowering

(Effectiveness)

Reduced

e-GFR

( <45/<30 mlmin)

Hypo-

glycemia

Risk

Body

WeightApplication Costs

SGLT-2

Inhibitors - + /- oral $$

GLP-1 R

Agonists () + /- Injection $$$

Metformin (long-term) + /- oral $

DPP-4

Inhibitors + /+ oral $$

Insulin

(basal) + /+ Injection

$ -

$$Sulfonyl-

urea -/- oral $

Swiss Recommendations 2016

www.sgedssed.ch

– Priority: No Hypoglycemia

Classes

Reduction

cardiovascular

complications

Relative HbA1c

Lowering

(Effectiveness)

Reduced

e-GFR

( <45/<30 mlmin)

Hypo-

glycemia

Risk

Body

WeightApplication Costs

Metformin (long-term) + /- oral $

SGLT-2

Inhibitors - + /- oral $$

GLP-1 R

Agonists () + /- Injection $$$

DPP-4

Inhibitors + /+ oral $$

Insulin

(basal) + /+ Injection

$ -

$$Sulfonyl-

urea -/- oral $

Swiss Recommendations 2016

– Priority: Costs

www.sgedssed.ch

Classes

Reduction

cardiovascular

complications

Relative HbA1c

Lowering

(Effectiveness)

Reduced

e-GFR

( <45/<30 mlmin)

Hypo-

glycemia

Risk

Body

WeightApplication Costs

Metformin (long-term) + /- oral $

Sulfonyl-

urea -/- oral $

Insulin

(basal) + /+ Injection

$ -

$$SGLT-2

Inhibitors - + /- oral $$

DPP-4

Inhibitors + /+ oral $$

GLP-1 R

Agonists () + /- Injection $$$

www.sgedssed.ch

1. Insulin Deficiency?

2. eGFR < 45/30 ml/min?

3. Cardiovascular Disease?

4. Heart Failure?

Swiss recommendations 2016

4 clinical questions

Question 1:

Is there insulin deficiency?

SGLT-2

Inhibitoro

Metformin GLP-1

RA

DPP-4

inhibitor

Insulin Sulfonyl-

urea

Insulin

Deficiencyo o o o + o

Symptomatic

Hyperglycemia

+

Metabolic

Decompensation

• Polyuria

• Polydipsia

• Weight Loss

• Volume Depletion

Insulin

1. SSED/SGED guidelines. 2016 update.

www.sgedssed.ch

Insulin use in type 2 diabetes in SwitzerlandIncreasing need for insulin with advancing kidney

failure

Insulin need (27-50%)

1 359 patients

(mean age 66.5 ± 12.4 years)

included by

109 primary care physicians

Swiss Med Wkly. 2016 Feb 28;146:w14282

Diabetes Treatment with CKD in Switzerland

CKD e-GFR <60 ml/min: 22.4%

CKD 4+5: eGFR

< 30 ml/min?

2.4 % of all patients

Swiss Med Wkly. 2016 Feb 28;146:w14282

CKD 3b: eGFR

< 45 and >30 ml/min?

6.1 % of all patients

CKD 3a: eGFR

< 60 and > 45 ml/min?

13.9 % of all patients

DPP-4

Inhibitor

Basal

Insulin

Metformin

(1/2 dose)

+SGLT2-I. or

GLP-1 RA

DPP-4 I.

Basal-Insulin

Metformin

+SGLT2-I. or

GLP-1 RA

DPP-4 I. /Glicazide

Basal-Insulin

Early combination

Swiss recommendations 2016Asymptomatic with high risk for cardiovascular event

3. Cardiovascular Disease?

yes

Metformin+

SGLT2 I.

Metformin+

GLP-1 RA

BMI > 28

~25/50% of all patients with T2D

>13 or 7 fold increased risk for

CHD and stroke events

Eur Heart J. 2008;29(18):2244-2251. doi:10.1093/eurheartj/ehn279

Predict Study

(589 Patients (50-70 years old:

T2D + no cardiovascular disease):

Coronary Artery Calcium Score (CACS)

Follow-up: 4 years; first CHD + stroke event

Relative

Risk

Percentage

of

population

1

4

7.1

8.4

13.8

51%

77%

22%

Swiss recommendations 2016Symptomatic cardiovasular disease?

3. Cardiovascular Disease?

yes

Metformin+

SGLT2 I.

Metformin+

GLP-1 RA

BMI > 28

• 1.9 Million Individuals > 30 years and

free of cardiovascular disease

• Follow-up: 5.5 years

• Endpoint: First occurence of

cardiovascular disease event

• Type 2 Diabetes (n=34‘198)

• 6137 events = 17.9% of population

• Most frequent: PAD 16.2% and

heart failure 14.1%

• No Diabetes

• 107’501 events = 5.7% of population

• Heart failure 12.1% and PAD: 9.2%

Lancet Diabetes Endocrinol. 2015 Feb; 3(2): 105–113

Cardiovascular disease in individuals

without and with type 2 diabetes?

Lancet Diabetes Endocrinol. 2015 Feb; 3(2): 105–113

16.2% peripheral arterial disease

14.1% heart failure

11.9% stable angina

11.5% non-fatal MI

10.3% stroke not specified

10.2% coronary disease not spec.

8.4% transient ischemic attack

5.1% ischemic stroke

1.0% aortic aneurysm

4.2% unheralded coronary death

4.0% unstable angina

1.6% arrhythmia or sudden cardiac death

1.4% intracerebral hemorrhage

1.0% aortic aneurysm

0.2% subarachnoid hemorrhage

9.4%

12.2%

9.3%

9.4%

14.1%

11.4%

4.9%

4.7%

5.2%

10.2%

3.0%

2.1%2.8%1.2%

Swiss recommendations 2016Symptomatic cardiovasular disease?

Rawshani A. et al, NEJM 2017, 376: 1407-18

• Swedish National Diabetes Register

• 457’473 individuals with type 2 diabetes

• Age: 65 years

• Coronary Heart Disease: 17.3%

• Acute Myocardial Infarction: 9.1

• Stroke: 6.6%

• Amputation: 0.4%

• Atrial fibrillation 7.6%

• Heart failure: 6.6%

24.3%

4th clinical question:

Asymptomatic Heart Failure?

1. SSED/SGED guidelines. 2016 update.

581 Patients >60 years with T2D

and no none heart failure in primary care

Diabetologia. 2012 Aug; 55(8): 2154–2162

HFpEF: 22.9%

HFrEF: 4.8%27.6%

Asymptomatic, diagnosed

with echocardiography

HFpEF: 22.9%HFrEF: 4.8%

∼25% of Patients >60 years have asymptomatic heart failure

4th clinical question: Symptomatic Heart Failure?

• Diagnosed clinically?

– 9591 individuals with type 2 diabetes

– Kaiser Permanente, Oregon, USA

– 64 years old

– 4.8 years diabetes duration

– 25% with coronary heart disease

– 52% with hypertension

– 19.7% on insulin

• Prevalence

– 11.8% vs. 4.5% (without diabetes)

• Incidence per year

– 7.7% vs. 3.4% (without diabetes)

Age = major risk factor

Prevalence

45-54 yrs: 3.3%

55-64 yrs: 6.8%

65-74 yrs: 13.5%

2x

2x

Incidence

45-54 yrs: 1.0%

55-64 yrs: 2.6%

65-74 yrs: 3.4%

Nichols GA et al. Diabetes Care 2001; 24: 1614-19

1st step: individual HbA1c-Target

2nd step: best individual therapy for patients:

Setting which priorities?

3rd step: Think in drug classes: choose the

substance with the best evidence

Classes+Substances Product Name Combination with Metformin

Biguanides

Metformin Glucophage® or Generics

SGLT-2-Inhibitors

Canagliflozin Invokana® (2x mehr Amputationen) Vokanamet®

Dapagliflozin Forxiga® Xigduo® XR*

Empagliflozin Jardiance® Jardiance Met®

DPP-4-Inhibitors

Alogliptin Vipidia® Vipdomet®

Linagliptin Trajenta® Jentadueto®

Saxagliptin Onglyza® Kombiglyze® XR*

Sitagliptin Januvia®, Xelevia® Janumet®, -XR*, Velmetia®

Vildagliptin Galvus® Galvumet®

Sulfonylurea

Gliclazide Diamicron® or Generika

GlibenclamideDaonil®/Semi-Daonil® or

GenercsGlucovance®/- mite

Glimepiride Amaryl® or Generics

Dru

gs in

red

ha

ve

be

tter

evid

en

ce

for

red

uctio

nofm

orta

lity, as

we

lla

s

mic

ro-a

nd

ma

cro

-va

scu

lar

co

mp

lica

tion

sand

sh

ou

ldbe

pre

fere

d

Class/Substance Product Name Combination

GLP-1 Rezeptor Agonists (Glucagon-Like Peptide 1)

Exenatide Byetta® (2x daily)

Exenatide Slow Release Bydureon® Pen (1x weekly)

Liraglutide Victoza® (1x daily) + Insulin Degludec: Xultophy®

Semaglutide

Dulaglutide Trulicity® (1x weekly)

Insulin analogs, long-acting

Degludec* Tresiba® + Liraglutid: Xultophy®

Detemir Levemir®

Glargine Lantus®

- Glargine 300 Toujeo® SoloStar® (Insulin tested, but not longer duration)

- Glargine-Biosimilar Abasaglar®

Human insulin, intermediate duration of action

NPH Huminsulin, Insulatard

Insulin analogs, short-acting

Lispro Humalog®

Aspart NovoRapid®

Glulisin Apidra®

Premixed insulins with short- and long-acting insulin analogs or NPH-Insulin

Lispro Humalog® Humalog® Mix (NPH-Insulin)

Aspart NovoRapid® NovoMix® (NPH Insulin)

Degludec/Aspart NovoRapid® Ryzodeg® (Degludec)

Dru

gs in

red

ha

ve

bette

re

vid

en

ce

for

red

uctio

nof

mo

rtality, a

nd

mic

ro-a

nd

macro

-vascula

rcom

plic

atio

ns

an

dshould

be

pre

fere

d

Swiss recommendations 2016Swiss Society of Endocrinology and Diabetology

2. eGFR < 30

ml/min?

DPP-4

Inhibitors

Basal

Insulin

3. Cardiovascular Disease?

yesno

Metformin+

SGLT2 I. Metformin+

GLP-1 RA

Metformin +

DPP-4 I.

Metformin+

SGLT2 I.

Metformin+

GLP-1 RA

+ DPP-4 I. or

Gliclazide or

Basal Insulin

+ Gliclazide or

Basal Insulin

+ Gliclazide

or Basal

Insulin

4. Heart Failure?

Metformin+

SGLT2 I.

+ DPP-4 I.

Basal

Insulin

1. Insulin

Deficiency?Basal Insulin

Premixed-InsulinBasal

Bolusor

or

or

Basal Insulin +

GLP-1 RA (Xultophy®)

~20-25% of all patients(~50% asymptomatic)

~ 10% of all patients(~25% asymptomatic)

2.4% of all patients

~25% of all patients

6.1%: e-GFR 30-45

13.9%: e-GFR 45-60

~25% e-GFR < 60

www.sgedssed.ch