LA STRATEGIA TERAPEUTICA NEL PAZIENTE ANZIANO Prato.pdf · •Farmacoterapia multipla e complessa – interazione tra ... Can J Diabetes.2003;27:128 –140; 7McEwan P, et al. Diabetes

Stefano Del Prato

LA STRATEGIA TERAPEUTICA

NEL PAZIENTE ANZIANO

Diabetes Mellitus in elderly subjects

0

20

40

60

80

100

120

140

160

180

200

20-44 45-64 65+

Estim

ate

d N

. of

people

with D

M

2010 2030

0

2

4

6

8

10

12

14

<2

0

20-2

4

25-2

9

30-3

4

35-3

9

40-4

4

45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80+

Pre

vale

nce

of D

M in U

SA

(%

)

Global diabetic

population

Distribution of DM in age-

groups at diagnosis.

Vacante M et al. Arch Gerontol Geriatr. 2011;53:113-9

Diabetes Mellitus in elderly subjects

0

20

40

60

80

100

120

140

160

180

200

20-44 45-64 65+

Estim

ate

d N

. of

people

with D

M

2010 2030

0

2

4

6

8

10

12

14

<2

0

20-2

4

25-2

9

30-3

4

35-3

9

40-4

4

45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80+

Pre

vale

nce

of D

M in U

SA

(%

)

Global diabetic

population

Distribution of DM in age-

groups at diagnosis.

Vacante M et al. Arch Gerontol Geriatr. 2011;53:113-9

Narayan KM et al. Diabetes Care 2006;29:2114-6

Impact of recent increase in incidence on future

diabetes burden – U.S.A. 2005 - 2050

0

5

10

15

20

25

0-19 20-34 35-49 50-64 65-79 ≥80 Total

Perc

ent

Age (years)

Male Female

Miccoli R. 2012 Personal Communication

Diabetes prevalence per age group –

ARNO-Diabete 2010

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Diabetes No Diabetes

≥80

65-79

50-64

35-49

20-34

0-19

Age distribution in the population with or

without diabetes - ARNO-Diabete 2010

Age (years)

Miccoli R. 2012 Personal Communication

NHANES 1999-2006 - Diabetes, Comorbidities,

A1c and Functional Disability in Older Adults

0

10

20

30

40

50

60

70

80

GPA LEM IADL ADL LSA

Perc

ent

with d

ifficulty

Effect of Diabetes

Contribution to

excess OR (%)

LEM 85

LSA 85

GPA 79

IADL 72

ADL 59

GPA: General Physical Activity; LEM: Lower Extremity Mobility; IADL: Instrumental Activity of Daily Life;

ADL: Activity of Daily Life; LSA: Leisure and Social Activity

Kalyani RR et al. Diabetes Care 2010;33:1055

Comorbidities and A1c

NHANES 1999-2006 - Diabetes, Comorbidities,

A1c and Functional Disability in Older Adults

0

10

20

30

40

50

60

70

80

GPA LEM IADL ADL LSA

Perc

ent

with d

ifficulty

Effect of Diabetes

Contribution to

excess OR (%)

LEM 85

LSA 85

GPA 79

IADL 72

ADL 59

GPA: General Physical Activity; LEM: Lower Extremity Mobility; IADL: Instrumental Activity of Daily Life;

ADL: Activity of Daily Life; LSA: Leisure and Social Activity

Kalyani RR et al. Diabetes Care 2010;33:1055

Comorbidities and A1c

Chang AM et al. Am J Physiol Endocrinol Metab, 2003

Progression

to IGT and

T2DM

Impaired

adaptation:

No

insulin

INSULIN

RESISTANCE

Decreased physical

activity

Increased adiposity

Age effects

on insulin action

Increased adiposity

Medications

Genetics

Coexisting illness

IMPAIRED

INSULIN

SECRETION

Medications

Genetics

Coexisting illness

Age effects on

beta-cell

Pathogenesis of T2DM in aging

Diabetes Risk Factors in

Aging

Zamboni M et al. Nutr Metab Cardiovasc Dis, 2008

A new link between aging and diabetes:

the sarcopenic obesity

The general population is ageing

DM has a high prevalence, which increases substantially with

age

The socio-economic burden of DM will only continue to grow

DM is considered to lead to accelerated aging

The diabetic population has a high prevalence of geriatric

syndrome

DM emerged as a significant predictor of progression in any

frailty characteristics

Rationale for treating elderly diabetic

people

To keep patients aymptomatic

To prevent either acute or chronic

complications

To preserve QoL

To avoid adverse drug reactions

Treatment goals in elederly diabetic

subjects

To keep patients aymptomatic

To prevent either acute or chronic

complications

To preserve QoL

To avoid adverse drug reactions

Treatment goals in elederly diabetic

subjects

Il caso di Aristide…..

77 anni con 4 anni di storia di T2DM. Anamnesi positiva per ischemia cardiaca e

osteoartrite degenerativa della colonna

Terapia

• Metformina 1 g bid, aspirina 75 mg qd, bisoprolol 5 mg qd, ISMO 10 mg bid, ramipril 5

mg bid, simvastatina 40 mg qd

All’obiettività:

• Peso 95 kg; BMI 33 kg/m2; PA140/75 mmHg; polso 65 bpm

Laboratorio:

• HbA1c: 8.6% (70 mmol/mol)

• eGFR: 42 mL/min/1.73 m2

• Total cholesterol: 151 mg/dl (3.9 mmol/L)

• Low-density lipoprotein cholesterol: 77 mg/dl (2.0 mmol/L)

• High-density lipoprotein cholesterol:42 mg/dl (1.1 mmol/L)

• Plasma triglyceride: 185 mg/dl (2.1 mmol/L)

BMI=body mass index; HbA1c=haemoglobin A1c.

Secondo voi, qual’è la principale considerazione da

fare rispetto alla terapia del Sig. Aristide?

1. Evitare l’ipoglicemia

1. Evitare l’aumento del peso

2. Ridurre i potenziali rischi di interazione tra farmaci

3. Valutare la sicurezza di ogni ulteriore trattamento

farmacologico

4. Altro

Glycaemic control and all-cause

mortality – A U shaped curve?

4

5

6

7

8

9

10

6,42 6,94 7,27 7,54 7,82 8,11 8,44 8,85 9,41 10,47

Perc

ent

death

over

12 y

era

s

Deciles of HbA1c

100

90

80

70

60

50

40

Age a

t baselin

e (

years

)

Currie JE et al Lancet 2010; 375:481



4

5

6

7

8

9

10

6,42 6,94 7,27 7,54 7,82 8,11 8,44 8,85 9,41 10,47

Perc

ent

death

over

12 y

era

s

Deciles of HbA1c

100

90

80

70

60

50

40

Age a

t baselin

e (

years

)




0

1

2

3

4

5

6

7

6,42 6,94 7,27 7,54 7,82 8,11 8,44 8,85 9,41 10,47

Perc

ent w

ith c

rea

tini

ne >

13

0 µ

mol/

L

Deciles of HbA1c


Intervention trials in T2DM patients –

Age at entry

TRIAL Age recruitment

criterion AGE AT ENTRY

UKPDS 25-65 54

UKPDS-FU 25-65 62

ProACTIVE 35-75 62

ADVANCE >55 66±6

ACCORD 40-79 62±7

VADT 45-79 60

Recommendations for target glycemic

levels in elderly T2DM patients

Glycaemic targets in diabetes.

The ADA/AHA position statement

A1c <7.0%

• Short duration of diabetes

• Long life expectancy

• No significant

cardiovascular disease

• A1c >7.0%

• History of severe

hypoglycemia

• Limited life expectancy

• Long-standing diabetes

• Advanced micro- and

macrovascular

complications

Skyler J. et al Diabetes Care 2009;32:187

MAY GAIN ADDITIONAL

MICROVASCULAR BENEFIT AS

WELL AS MACROVASCULAR

PROTECTION

Patient’s phenotype B=body weight

C=complications

D=duration

A1c >7.0%

A= age

The A1C and ABCD of glycaemia management in

T2DM: a physician’s personalized approach

YOUNG MIDDLE

AGE ELDERLY

– – – + + +

<6.0 <6.5 <6.5 6.5-7.0 <7.0 7.0-8.0

Age

Complications* or

Disease duration

>10yrs

A1c target

>9.0 A1c at

diagnosis

Initial

therapy

<9.0%

Metformin Consider

insulin

*Micro- and macrovascular complications Pozzilli P …. Del Prato S Diabetes Metab Res Rev 2010; 26:239

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach

Diabetes Care – Diabetologia June 2012

Quale sarebbe la vostra opzione

terapeutica per il Sig. Aristide?

1. Sulfonilurea

2. Glinide

3. Pioglitazone

4. Insulina

5. Agonista del recettore GLP-1

6. Inibitore DPP-4

DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1.

Alcuni problemi nella cura di Aristide

• Ipoglicemia

• Peso corporeo

• Sottostante malattia cardiovascolare

• Farmacoterapia multipla e complessa – interazione tra

farmaci

• Insufficienza renale

With increasing age, potential reaction time between awareness and onset of

symptoms is decreased, contributing to an increased risk for asymptomatic

hypoglycaemia and greater susceptibility to cognitive impairmenta,1,2

Thresholds for hypoglycaemia symptoms

vary with agea,1,2

aBased on data in non-diabetic patients with no family history of diabetes.

1Zammitt NN, Frier BM. Diabetes Care. 2005;28:2948–2961; 2Matyka K, et al. Diabetes Care. 1997;20:135–141.

Blo

od

glu

co

se

co

nce

ntr

ation

1

(mg/d

L)

36

45

54

63

72

Men aged 23 ± 2 years (n=7)

Greater reaction

time for corrective

action

Hypoglycaemic

awareness

Onset of

cognitive dysfunction

36

45

54

63

72

Men aged 65 ± 3 years (n=7)

Less reaction time

for corrective

action

Blo

od

glu

co

se

co

nce

ntr

ation

1

(mg/d

L)

Hypoglycaemic

awareness

Onset of

cognitive dysfunction

Lifestyle risk factors

• Poor nutrition or fasting

• Prolonged physical exercise

• Alcohol (ethanol)

Drug risk factors

• Use of SU and / or insulin

• Drug interactions with SUs

Patient risk factors

• Advanced age

• Recent hospitalisation

• Intercurrent illness

• Chronic liver, renal or


• Endocrine deficiency (thyroid,

adrenal, pituitary)

• Loss of normal counter-regulation

• Hypoglycaemic unawareness

SU=sulfonylurea.

Adapted from Chelliah A, Burge MR. Drugs Aging. 2004;21:511–530.

Hypoglycaemia is a major challenge in

the treatment of diabetes in the elderly





Drug risk factors




• Advanced age






adrenal, pituitary)



SU=sulfonylurea.








Drug risk factors




• Advanced age






adrenal, pituitary)



SU=sulfonylurea.








Drug risk factors




• Advanced age






adrenal, pituitary)



SU=sulfonylurea.




The consequences of hypoglycaemia

1Whitmer RA, et al. JAMA. 2009;301:1565–1572; 2Bonds DE, et al. BMJ. 2010;340:b4909; 3Barnett AH. Curr Med Res Opin.

2010;26:1333–1342; 4Jönsson L, et al. Value Health. 2006;9:193–198; 5Foley JE, Jordan J. Vasc Health Risk Manag. 2010;6:541–548; 6Begg IS, et al. Can J Diabetes. 2003;27:128–140; 7McEwan P, et al. Diabetes Obes Metab. 2010;12:431–436.

HYPOGLYCAEMIA

Cardiovascular

complications3

Weight gain by

defensive eating5

Coma3

Increased risk

of car accident6

Hospitalisation

costs4

Loss of

consciousness3

Increased risk

of seizures3

Death2,3

Increased risk

of dementia1

Reduced

quality of life7

Severe hypoglycaemia accounts for almost 20% of

all hospitalisations for T2DM in the elderly

T2DM=type 2 diabetes mellitus.

Greco D, et al. Exp Clin Endocrinol Diabetes. 2010;118:215–219.

Decompensated

diabetes

39%

Intercurrent illness

14%

Acute

cardiovascular

events 14%

Chronic

complications

of diabetes 17%

Severe

hypoglycaemia

17%

Budnitz DS et al. N Eng J Med, 2012

Estimated rates of emergency hospitalizations for

adverse drug events in older U.S. adults, 2007 - 2009

ADVANCE – Association of severe hypoglycemia with

the risk of an adverse clinical outcome or death

Zoungas S. et al N Engl J Med 2010;363:1410

Clinical criteria Biological criteria

ApoE carriers

Plasma osmolarity (> 300

mOsm/l)

Low serum albumin (< 38 g/l)

Increased CRP

Increased IL6

Low total cholesterol

Sarcopenia is a major

cause of disability and

frailty in the elderly

Xue QL. Clin Geriatr Med, 2011; Bourdel-Marchasson I et al. Diabetes Metab, 2005

Frailty and vulnerability

The risk of severe hypoglycaemia: post hoc

epidemiological analysis of the ACCORD study

0

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

Diabetes duration (years)

BMI (kg/m2)

Serum creatinine ( mol/l)

*History of peripheral neuropathy (yes vs. no); **per 1 year increase

P=0.03

P=0.01

P<0.0001

P<0.0001

P<0.0001

P<0.03

P<0.0001

Miller ME et al . BMJ 2010;340: b5444

A B C C D

Prevalence of hypoglycaemia in T2DM is

greatest in patients treated with insulin therapy

Miller D, et al. Arch Intern Med. 2001;161:1653-9.

Patients

report

ing h

ypogly

caem

ia (

%)

* P<0.05 vs diet alone; ** P<0.001 vs diet alone; ***P<0.05 vs insulin alone; § P<0.01 vs insulin alone

0

10

20

30

40

50

60

70

**

Prevalence of hypoglycaemia in T2DM is

greatest in patients treated with insulin therapy

Miller D, et al. Arch Intern Med. 2001;161:1653-9.

Patients

report

ing h

ypogly

caem

ia (

%)

* P<0.05 vs diet alone; ** P<0.001 vs diet alone; ***P<0.05 vs insulin alone; § P<0.01 vs insulin alone

0

10

20

30

40

50

60

70

* *

**

**

***

Incidence of hypoglycaemia with different

glucose-lowering agents for T2DM

Bolen S, et al. Ann Intern Med. 2007;147:386-399.

AMI, stroke, CHF and all-cause mortality in elderly

medicare patients treated with pio- or rosiglitazone

Graham at al., JAMA 2007; 304:411

Bone fracture!

Heart failure!

Barzilai N et al. CMRO, 2011

Efficay and tolerability of sitagliptin

monotherapy in elderly T2DM patients

Sitagliptin Placebo

Overall AE (%) 46.1 52.9

Severe AE (%) 6.9 13.5

Hypoglycaemia (%) -- --

N=206; mean age=72 years

Vildagliptin in the very elderly T2DM patients

-1,5

-1,0

-0,5

0,0

0,5

1,0

1,5

MonoRx* Met Add-on**

(Pe

rce

nt)

-1,0

-0,8

-0,6

-0,4

-0,2

0,0

MonoRx Met Add-on

(kg

)

0

10

20

30

40

50

60

MonoRx Met Add-on

(Perc

ent

)

Monotherapy Add-on to met

≥75 yr <75 yr ≥75 yr <75 yr

N (%) N (%) N (%) N (%)

Any

events 0 (0) 8 (0.3) 0 (0) 0 (0)

Severe

events 0 (0) 0 (0) 0 (0) 0 (0)

HBA1c Body Weight

Achieving A1c ≤7.0 Hypoglycemia

Age ≥75 yr (MonoRx, N=62; Add-on, N=25) Age <75 yr (MonoRx, N=2303; Add-on, N=910)

Schweizer A et al. Diabetes Obes Metab 2011; 13:55

GLP1 receptor agonists in elderly T2DM patients

• Exenatide

• 282 patients aged ≥65 years in the registration trials – No

difference in efficacy-safety between eledrly and younger patients

• 165 patients aged ≥70 years in EPAR*– Greater decrease in

HbA1c and weight compared with younger patients

• Only 36 patients aged ≥70 years – No meaningful evaluation

possible

• Liraglutide

• LEAD 1 – age apparently non affecting efficacy

• EPAR assessed data by age class – No difference in efficacy, but

AE increased with age, GI AE in particular

• Only 40 patients aged ≥70 years** – No meaningful evaluation

possible

*EPAR – European Public Assessment Report; ** 40 patients per liraglutide dose (1.2 and 1.8 mg qd)


• Ipoglicemia

• Peso corporeo




farmaci

RIACE Study Group, unpublished data

0

20

40

60

80

100

≤45 n. 113 (21.4%)

n. 528

46-60 n. 1,067 (26.8%)

n. 3,986

61-75 n. 3,100 (37.0%)

n. 8,374

>75 n. 1,628 (56.4%)

n. 2,885

eGFR <60 ml/min Both Albuminuria

Perc

ent

The Renal Insufficiency And Cardiovascular Events

(RIACE) Italian Multicentre Study

Snyder RW, Berns JS. Semin Dial. 2004;17:365-70.

Recommendations for altering therapy in case of

reduced glomerular filtration rate (GFR):

Insulin (rough rule of thumb) › GFR 10–50 ml/min, reduce insulin dosage by 25%

› GFR <10 ml/min, reduce insulin dosage by 50%

Avoid metformin and miglitol

Reduce dose and use with caution: glibenclamide;

glimepiride; nateglinide; acarbose

Impaired renal function and risk of drug-

induced hypoglycaemia

Snyder RW, Berns JS. Semin Dial. 2004;17:365-70.

Recommendations for altering therapy in case of

reduced glomerular filtration rate (GFR):

Insulin (rough rule of thumb) › GFR 10–50 ml/min, reduce insulin dosage by 25%

› GFR <10 ml/min, reduce insulin dosage by 50%

Avoid metformin and miglitol

Reduce dose and use with caution: glibenclamide;

glimepiride; nateglinide; acarbose

Impaired renal function and risk of drug-

induced hypoglycaemia

Although the risk of lactic acidosis on metformin is 10–20 times lower than

that on phenformin and does not differ from the risk in patients not taking

the drug, this agent still carries the historic burden of its predecessors. It is

even doubtful whether metformin plays a causal role in the pathogenesis of

lactic acidosis at all……….. We believe that standard contraindications to

the use of metformin should be relaxed, and that the benefits of reducing

the number of patients excluded from using it would by far outweigh the

potential risks. We propose removal of the following contraindications from

the list:

1. old age;

2. chronic renal insufficiency (as long as GFR >40 ml/min);

3. chronic heart failure (NYHA stages I and II); and

4. discontinuation of metformin therapy 2 days before surgery and i.v.

contrast medium administration.

Chan J.C.N. et al Diabetes, Obesity & Metabolism, 2008

Safety and efficacy of sitagliptin in T2DM

patients and chronic renal insufficiency

0

5

10

15

20

25

Sitagliptin Placebo/Glipizide

Pa

tie

nts

re

po

rtin

g h

yp

os

(%)

52-week efficacy and safety study of saxagliptin

(2.5 mg) in T2DM patients with renal impairment

-1,2

-1

-0,8

-0,6

-0,4

-0,2

0

0,2

0,4

Moderate Severe ESRD

HbA

1c (

%)

0

5

10

15

20

25

30

35

40

45

Moderate Severe ESRD

Patients

report

ed h

ypogly

cem

ia (

%)

Baseline HbA1c (%) 8.5 8.04 8.65

Nowicki M et al. Int J Clin Pract 2011; 65:1230

Tolerability and efficacy of vildagliptin in T2DM

patients with moderate or severe renal insufficiency

• Primary objective: to evaluate the safety and tolerability of vildagliptin (50 mg once

daily) vs placebo as monotherapy or add-on therapy to other antidiabetic drugs in

patients with T2DM and moderate or severe renal impairment during

24 weeks of treatment

• Key exploratory objective: to evaluate the efficacy of vildagliptin vs placebo in HbA1c

and FPG reduction from baseline after 24 weeks of treatment

aRandomised: patients must remain on their current antidiabetic therapy (stable dose for at least 4 weeks prior to visit 1) or remain untreated for

the duration of the study if patient is not on antidiabetic therapy at study entry (unless patient meets criteria for rescue medication).

FPG=fasting plasma glucose; HbA1c=haemoglobin A1c; T2DM=type 2 diabetes mellitus.

Data on file, Novartis Pharmaceuticals, LAF237A23137.

Placebo + current therapy (n=226)

Vildagliptin 50 mg once daily + current therapy (n=289)

Placebo run-in plus stable

dose of

current therapya

Period I Period II

24 weeks’ double-blind treatment 2 weeks

N=525

Lukashevich V et al Diabet Obes Metab 2011;13:942

aNumber of patients ≥65 years with moderate RI were 113 (vildagliptin) and 102 (placebo) and with severe RI were 64 (vildagliptin) and 46

(placebo).

AEs=adverse events; RI=renal impairment; SAEs=serious adverse events; vilda=vildagliptin.

Moderate RI Severe RI

Preferred term, n (%) Vilda 50 mg

N=163

Placebo

N=129

Vilda 50 mg

N=124

Placebo

N=97

Hypoglycaemic AEs 28 (17.2) 15 (11.6) 19 (15.3) 12 (12.4)

Hypoglycaemic AEs in patients

≥65 yearsa 13 (11.5) 12 (11.8) 10 (15.6) 9 (18.8)

Grade 2 events 3 1 1 2

Suspected Grade 2 events 1 1 1 0

GFR (MDRD) (mL/min/1.73 m2)

Mean Baseline (BL) 39.3 40.3 21.9 20.9

Mean change from BL 0.9 0.6 -1.5 -1.1

Median change from BL -0.1 -0.1 -1.3 -1.9




-1,0

-0,8

-0,6

-0,4

-0,2

0,0

Moderate RI

*P <0.0001 vs placebo. Full analysis set. BL=baseline; HbA1c=haemoglobin A1c; RI=renal impairment; T2DM=type 2 diabetes mellitus.

Severe RI

-1,0

-0,8

-0,6

-0,4

-0,2

0,0

Vildagliptin 50 mg once daily Placebo

BL= 7.86 7.79

Mean Change from

Baseline to End Point

Between-treatment

Difference vs Placebo

N= 157 128

*

Ad

juste

d M

ea

n C

ha

ng

e fro

m

Ba

se

line

in H

bA

1c (

%)

BL= 7.69 7.65

N= 122 95

* A

dju

ste

d M

ea

n C

ha

ng

e fro

m

Ba

se

line

in H

bA

1c (

%)

Mean Change from

Baseline to End Point

Between-treatment

Difference vs Placebo




MILD MODERATE SEVERE ESRD

SITAGLIPTIN 100 mg qd 50 mg qd 25 mg qd 25 mg qd

VILDAGLIPTIN 50 mg bid 50 mg qd 50 mg qd 50 mg qd*

SAXAGLIPTIN 5 mg qd 2.5 mg qd 2.5 mg qd* Not recommended

EXENATIDE Usual dose Caution in dose increase Not recommended Not recommended

LIRAGLUTIDE Usual dose Not recommended Not recommended Not recommended

Incretins in T2DM patients with impaired renal function

*Cautious use


• Ipoglicemia

• Peso corporeo




farmaci

0

10

20

30

40

50

60

70

80

90

100

Gruppi di farmaci più prescritti nei pazienti

con diabete – ARNO 2010

Claritromicina i

Eritromicina i

Fluconazolo i

Ketoconazolo i

Rifampicina h

Metoprololo

(s)

Warfarin (s)

Diltiazem (s)

Atorvastatina (s)

Rosuvastatina (s)

Simvastatina (s)

Desametazone h

Diclofenach

Carbamazepina h

Fenobarbital h

Fentoina h

Fluoxetina i

Midazolam (s)

(s) – substrato; i – inibitore; h – induttore del citocromo p-450

Vildagliptin Sitagliptin Saxagliptin

Substrate forCYP3A4 No Low Yes

CYP3A5 No No Yes

CYP2C8 No Very low No

Dose proportion Yes Yes Yes

Meal effect No No No

Drug interaction No No Yes

Dose reduction with

CYP3A4 inhibitors No No Yes (2.5 mg)

Scheen A J. Diabetes, Obesity and Metabolism 2010; 12 (8):648–658

Interaction of DPP4 inhibitors with cytochrome p450

The choice of anti-hyperglycaemic agent should focus on:

Drug safety

Heart failure

Renal dysfunction

Bone fractures

Drug-drug interactions

Performance status

Strategies specifically minimising the risk of low

blood glucose may be preferred

In the elderly, the basic principle should be

“START LOW, GO SLOW”

Treatment in the elderly: summary

Documents

LA STRATEGIA TERAPEUTICA NEL PAZIENTE ANZIANO Prato.pdf · •Farmacoterapia multipla e complessa – interazione tra ... Can J Diabetes.2003;27:128 –140; 7McEwan P, et al. Diabetes