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

80 70 60 50 27.5% 35.5% 40 BMI>30 kg/m2 30 20 42.2% 38.3% BMI>25Kg/m2 10 0 2011 2025 Adapted from Data from Walls et al.,(2012),australian Health Survey

Percentage 30 25 Males Females 21.6 22.4 24.5 20 15 16.1 16.1 10 5 0 9.9 6.8 5.5 2.6 2.3 0.1 0.4 25-34 35-44 45-54 55-64 65-74 75+ Age group (years) Ausdiab 2006

Incidence (% per year) 2.0 1.8 1.6 Males Females All 1.4 1.6 1.2 0.8 0.8 0.7 0.8 0.4 0.4 0.4 0.4 0.0 Normal Overweight Obese Baseline BMI status Body mass index (BMI: weight/height 2 ) was categorised into three groups: (i) normal: BMI < 25.0 kg/m 2 ; (ii) overweight: 25.0 29.9 kg/m 2 ; and (iii) obese: 30.0 kg/m 2. Ausdiab 2006

Not enough insulin secreting cells to get the job done Insulin requirement is proportional to body mass Lose enough weight and lose the diabetes

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 Medication Cardiovascular risk factor management Co-morbidities : Sleep study Bariatric surgery discussion

Metformin Optimise Weight Loss BGL CSIRO Or VLCD Pharmacotherapy

Life Stage Obesogenic Environment Socioeconomic Status Genetics/Epi genetics Afferent Central Efferent Pathways BMI OSA/Medical /Psychiatric

Total Energy Intake Total Energy Expenditure Efferent system Central integrating TEF PAL/NEAT Afferent BMR

Readiness What 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 Metformin Sulfonylurea (SU)

Metformin Metformin Metiglinides Acarbose Sulfonylurea (SU) Thiazolidinediones (TZD)

Diabetic therapy Options Metformin Sulfonylurea (SU) DPP-4 inhibitor (DPP4i) GLP-1 receptor agonist DPP4i: Dipeptidyl peptidase-iv inhibitor; GLP-1: Glucagon-like peptide-1; SGLT2: Sodium-glucose co-transporter 2 Thiazolidinediones (TZD) SGLT2 inhibitor Insulin SGLT2 inhibitor Thiazolidinediones (TZD) Insulin GLP-1 receptor agonist 1. Inzucchi SE, et al. Diabetes Care 2012;35:1364 1379.

Weight neutral Diabetic therapy Options Metformin DPP-4 inhibitor (DPP4i) GLP-1 receptor agonist SGLT2 inhibitor SGLT2 inhibitor Insulin 1. Inzucchi SE, et al. Diabetes Care 2012;35:1364 1379.

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

Inhibit DPP-4 Inactivated by DPP-4 Increase GLP-1

Mean change in HbA 1c from baseline (%) 50 weeks 102 weeks Sita, Vilda, Saxa, Lina, Alogliptin HbA 1c reductions with saxagliptin + metformin at 50 weeks and 102 weeks *1,2 Saxagliptin 5mg + metformin n=191 Metformin + placebo n=179 Mean change -0.74% ** Mean change -0.72% ** n=15 observed, n=172 LOCF n=31 observed, n=184 LOCF Weeks Mean baseline HbA 1c 8.1%

Exenatide 2 +1.8 kg Change in body weight (kg) 1 0-1 * * * * Insulin glargine (Mean baseline body weight 88.3 kg) Byetta (Mean baseline body weight 87.5 kg) -2 * * +2.3 kg -3 0 2 4 8 12 18 26 Weeks Insulin glargine n = 267 266 261 253 251 246 244 Byetta n = 281 277 275 261 245 235 231 Adapted from Klonoff DC et al. Curr Med Res Opin 2008; 24: 275 86.

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109 kg HbA1c 6.9% Sita/MF 50/1000 mg bd???

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