Dr Karen McNeil

Consultant Endocrinologist

Aged 53

Type 2 Diabetes 2010

HbA1c 7.9%

ACR 5.3 mg/mmol

What treatment ?

MF 500 mg bd (misses midday dose)

Control• Symptoms, BGL

Complications• DR, DN, PN

Associations• Cardiovascular

• BMI……..

Weight history:• Onset, Peak, Now

• Diets, drugs, surgery

• What diet and exercise now

• Readiness

Complications• Sleep apnoea

• OA

• Cardiovascular etc

60 % of Australian adult males are

overweight or obese

Less than 16% of Australian men Gary’s

age have T2 DM or IGT

80% of patients with Type 2 DM are

overweight or obese

0

10

20

30

40

50

60

70

80

2011 2025

BMI>30 kg/m2

BMI>25Kg/m2

27.5%

42.2%

35.5%

38.3%

Adapted from Data from Walls et al.,(2012),Australian Health

Survey

0.1

2.6

6.8

16.1

21.6 22.4

0.42.3

5.5

9.9

16.1

24.5

0

5

10

15

20

25

30

25 - 34 35 - 44 45 - 54 55 - 64 65 - 74 75+

Males

Females

Age group (years)

Pe

rce

nta

ge

Ausdiab 2006

0.4

1.8

0.4

0.7

1.4

0.4

0.8

1.6

0.8

0.0

0.4

0.8

1.2

1.6

2.0

Normal Overweight Obese

Males

Females

All

Baseline BMI status

Inc

ide

nc

e (

% p

er

ye

ar)

Body mass index (BMI: weight/height2) was categorised into three groups: (i) normal: BMI < 25.0 kg/m2;

(ii) overweight: 25.0─29.9 kg/m2; and (iii) obese: ≥ 30.0 kg/m2.

Ausdiab 2006

Lose enough weight and lose the diabetes

Insulin requirement is proportional to body mass

Not enough insulin secreting cells to get the job done

BMI 37 kg/m2, 123 kg and 180 cm

BP 146/95

Full neck and crowded pharynx

Skin tags and slight acanthosis

Labs:• Combined dyslipidaemia

• ACR 5.6 mg/mmol

• eGFR 86

Perfect glycaemic control

• Target HbA1c < 7.0%

• Optimize MF and

• Weight loss

• MedicationCardiovascular risk factor managementCo-morbidities : Sleep studyBariatric surgery discussion

Metformin Optimise

Weight Loss

• BGL

• CSIRO

• Or VLCD

• Pharmacotherapy

Afferent

Central

Efferent

Pathways

BMI

Genetics/Epigenetics

‘Obesogenic’ Environment

Life Stage

Socioeconomic Status

OSA/Medical/Psychiatric

Total Energy Intake

Total Energy Expenditure

BMR

PAL/NEAT

TEF

Afferent

Central integrating

Efferent system

ReadinessWhat does success look like?

• To Gary

• To his doctor

• Medical management (‘3% successful’)

Calorie restriction• All diets work and don’t work/food based

• Or VLCD

GP Weight management Guidelines• “Ask and Assist……

Pharmacotherapy

30 minutes daily of at least moderate

intensity physical activity on most

days (Australian guidelines 1999)

(similar guideline) Physical activity

total of >150 mins per week (US, WHO

2008, 2010) ; Australia 2012

Cardiac assessment……..??

BMI 34 (113 kg)

HbA1c 7.8%

Still on metformin• Diet and exercise

• “Maxed out”

• Surgery

• Drug therapy options

• Oral vs injected

• What is metformin?

??? Your view

Gliptin?

SGLT2 Inhibitor?

Exenatide

Metformin

Sulfonylurea

(SU)

Metformin

Metformin

Sulfonylurea

(SU)

Metformin

Metiglinides

AcarboseThiazolidinediones

(TZD)

Metformin

Sulfonylurea

(SU)

Metformin

Metiglinides

AcarboseThiazolidinediones

(TZD)

1. Inzucchi SE, et al. Diabetes Care 2012;35:1364–1379.

DPP4i: Dipeptidyl peptidase-IV inhibitor; GLP-1: Glucagon-like peptide-1;

SGLT2: Sodium-glucose co-transporter 2

SGLT2 inhibitor

Sulfonylurea

(SU)

GLP-1 receptor

agonist

InsulinThiazolidinediones

(TZD)

DPP-4 inhibitor

(DPP4i)

Metformin

InsulinThiazolidinediones

(TZD)SGLT2 inhibitorGLP-1 receptor

agonist

Diabetic therapy

Options

1. Inzucchi SE, et al. Diabetes Care 2012;35:1364–1379.

SGLT2 inhibitor

GLP-1 receptor

agonist

DPP-4 inhibitor

(DPP4i)

Metformin

InsulinSGLT2 inhibitor

Weight neutral

Diabetic therapy

Options

Incretin based • Dipeptidyl peptidase- 4 inhibitor (DPP4-I)

‘gliptins’

• Glucagon-like peptide-1 analogue (GLP1A)

• Exenatide, liraglutide

Sodium-glucose Cotransporter-2• Dapagliflozin, empagliflozin

• ‘gliflozins’

Inactivated

by DPP-4

Inactivated

by DPP-4

Inhibit DPP-4

Increase GLP-1

Sita, Vilda, Saxa, Lina, Alogliptin

HbA1c reductions with saxagliptin + metformin at 50 weeks and 102

weeks*1,2

Mean baseline HbA1c 8.1%

Weeks

Me

an

ch

an

ge

in

HbA

1c

fro

m b

ase

line

(%)

Saxagliptin 5mg +

metformin n=191

Metformin + placebo

n=179

Mean change

-0.74%**

Mean change

-0.72%**

102 w

eeks

50

weeks

n=15 observed,

n=172 LOCF

n=31 observed,

n=184 LOCF

Klonoff DC et al. Curr Med Res Opin 2008; 24: 275−86.

Exenatide

2

1

0

-1

-2

-3

Ch

ang

e in b

od

y w

eig

ht

(kg)

Weeks

Insulin glargine

(Mean baseline body weight 88.3 kg)

+1.8 kg

+2.3 kg

Byetta

(Mean baseline body weight 87.5 kg)

**

*

*

*

*

Adapted from

0 2 4 8 12 18 26

Insulin glargine n = 267 266 261 253 251 246 244

Byetta n = 281 277 275 261 245 235 231

sglt2-endocrine-cme-grand-rounds-final-

9-638

109 kg

HbA1c 6.9%

Sita/MF 50/1000

mg bd

???

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