Navigating the New Options for the Management of Type 2 Diabetes Clinical Associate Professor Mark Kennedy Department of General Practice, University of Melbourne Chair, Primary Care Diabetes Society of Australia Medical Director, Northern Bay Health Disclosures I have previously received speaker s fees, travel support, medical writing grants or served on medical advisory committees for the following companies: Astrazeneca Australia Astrazeneca Global Boehringer-Ingelheim Australia Boehringer-Ingelheim Global Sanofi Aventis Eli-Lilly Takeda Glaxo MSD Bristol Myers Squibb Janssen Novartis NovoNordisk Primary Care Diabetes Society of Australia Diabetes Care For All By All 2 I have received no financial support from industry for the preparation of the content of this presentation Take Home Messages: Take Home Messages 2: Selecting anti diabetic medication is based on: Selecting anti diabetic medication ABCD (EFGH) Approach Consider: Individualized therapeutic targets Achieving HbA1c target while minimizing side effects, especially hypoglycaemia Individual medication risk benefit analysis: Patient preference Comorbidities and complications Drug characteristics BMI of Diabetes Considerations Glycaemic Status concern 3 4 Overview Set an A1c target - ADS guidelines Populations HbA 1c Setting an HbA1c target % SI units General 7% 53 mmol/l Diabetes of short duration and no clinical CVD Therapeutic algorithms The ABCD (EFGH) approach Case Studies Requiring lifestyle modification ± metformin 6.0% 42 mmol/l Requiring any antidiabetic agents other than metformin or insulin 6.5% 48 mmol/l Requiring insulin 7.0% 53 mmol/l Pregnancy or planning pregnancy 6% 42 mmol/l Diabetes of longer duration or clinical CVD (any therapy) 7.0% 53 mmol/l Recurrent severe hypoglycaemia or hypoglycaemia unawareness (any 8.0% 64 mmol/l therapy) Major co morbidities likely to limit life expectancy (any therapy) Symptomatic 5 1
Selecting the optimum HbA1c target 6% 7% 8% More stringent Approach to management of hyperglycaemia: Less stringent Patient attitude & expected treatment efforts Risks potentially associated with hypoglycaemia, other AEs Highly motivated, adherent, excellent self-care capacities Low Less motivated, non-adherent, poor self-care capacities High Disease duration Newly-diagnosed Long-standing Life expectancy Long Short Important comorbidities Absent Severe Established vascular complications Absent Severe Resources, support system Readily available Limited 7 8 Oral anti-diabetic agents and non-insulin injectables Class Generic name Brand name Biguanide Metformin Glucophage Sulfonylureas e.g. Glibenclamide (glyburide) e.g. Gliclazide e.g. Glimepiride Diabex Daonil Diamicron Amaryl α-glucosidase inhibitors Acarbose Glucobay Pioglitazone Actos DPP-4 inhibitors Saxagliptin Sitagliptin Vildagliptin Linagliptin Alogliptin Onglyza Januvia Galvus Trajenta Nesina Oral anti-diabetic agents and non-insulin injectables Class Generic name Brand name GLP-1 agonists Exenetide Exenetide Liraglutide Lixisenatide Byetta Bydureon Victoza Lyxumia Dapagliflozin Canagliflozin Empagliflozin Forxiga Invokana Jardiance 9 10 Benefits of Diabetic Medications -1 Property SU TZD DPP4i Glp1a Acarbose SGLT2i Efficacy - A1c FBG Post-prandial BG Durability of control Benefits of Diabetic Medications -2 Property SU TZD DPP4i Glp1a Acarbose SGLT2i Use in different duration of DM Convenience of dosing/delivery Early All All All All All All Injectable TDS Injectable Affordability Other benefits Rapid onset BP Improves fatty liver BP BP Empa- Reg Unlimited efficacy 11 12 2
Risks of Diabetic Medications - 1 Property SU TZD DPP4i Glp1a Acarbose SGLT2i Use with Use with Liver Failure Use/Risk in CVD Reduce dose dose dose dose dose? except Vildagliptin? (empagliflozin) Weight Gain Risks of Diabetic Medications - 2 Property SU TZD DPP4i Glp1a Acarbose SGLT2i Fractures? Heart Failure / Oedema GIT Symptoms saxagliptin? alogliptin sitagliptin (empagliflozin) Interactions 13 14 Risks of Diabetic Medications - 3 Property TZD DPP4i Glp1a SGLT2i Other Possible risks? bladder cancer? pancreatitis? pancreatitis Macular oedema HR Thrush DKA Hypovolaemia Choosing 2 nd and 3 rd line agents Aim to reduce HbA1c while minimizing side effects Weight gain Depends on: Patient preference Comorbidities and complications Drug characteristics 15 16 ABCD (EFGH) Approach A- Considerations 17 BMI of Diabetes Considerations Glycaemic Status concern 18 increases risks of: Hypovolaemia Cardiac failure Reduced beta cell function Osteoporosis 3
Range of weight change (kg) 24-May-16 B - BMI Considerations Range of weight change (kg) in response to diabetes medications 10 8 6 4 2 0 C Chronic Kidney Disease more common in severe SU and dose may need to be reduced best at end stage renal failure -2-4 -6 Sulfonylureas DPP-4 Alphaglucosidase inhibitors inhibitors Diabetes medications Metformin GLP-1 receptor agonist SGLT2 Inhibitor Linagliptin needs no dose adjustment Others need dose adjustment 20 D of Diabetes E UKPDS Study showed importance of intensive glycaemic control in early years of T2DM Accord Study showed need to loosen targets in diabetes of longer duration SUs less effective with longer duration diabetes (as beta cell function declines) more risky with established CVD Empagliflozin reduced CV death by 38% over 3.s Some concerns from observational studies about CVD safety of SUs 21 22 E Empa-Reg CV death F - considerations In Australia, choices limited by PBS availability more than TGA approval Most expensive to prescribe non-pbs are, and SGLT2 inhibitors 23 24 4
G Glycaemic Status Glycaemic lowering of all agents is greater at higher starting HbA1c Efficacy rating: 1. 2. 3. s 4. 5. 6. 7. H Concerns s and main causes of hypoglycaemia More prevalent with and longer duration of diabetes, and SGLT2 inhibitors unlikely to cause severe hypoglycaemia and cause minimal hypoglycaemia unless used with or SU 25 26 H Concerns Initial Case Avoid hypoglycaemia in these groups: Established CV disease Elderly patients Retinopathy (difficult doing SMBG) Living alone Short life expectancy unawareness Previous severe hypoglycaemia Some occupations 27 28 29 30 5
31 32 33 34 Case 3 Morbid Obesity Case 4 Older and CVD BMI 36 58 year old male 1s YES empagliflozin (Jardiance) 35 36 6
Case 5 Case 6 Severe hypoglycaemia 68 year old male 68 year old male egfr 52 egfr > 60 2s (Δ dose) 2s NO (Δ dose) NO +/- +/- YES 37 38 Case 7 Terminal breast cancer Take Home Messages: 78 year old female Selecting anti diabetic medication is based on: egfr > 60 3s NO Individualized therapeutic targets Achieve HbA1c target minimizing side effects, especially hypoglycaemia Individual medication risk benefit analysis Patient preference Comorbidities and complications Drug characteristics 39 40 Take Home Messages 2: Thank You Selecting anti diabetic medication ABCD (EFGH) Approach BMI of Diabetes Considerations Glycaemic Status concern Any Questions: 41 42 7
Please join us at Primary Care Diabetes Society of Australia www.pcdsa.com.au Free membership Free Online Clinical Journal including CPD modules Annual Conference Get Involved! In order to ask your question, please login now! Healthed.cnf.io 43 Primary Care Diabetes Society of Australia Diabetes Care For All By All You must have your own internet enabled device. 8