GLP-1 Receptor Agonists and SGLT-2 Inhibitors. Debbie Hicks

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1 GLP-1 Receptor Agonists and SGLT-2 Inhibitors Debbie Hicks Prescribing and Adverse Event reporting information is available at this meeting from the AstraZeneca representative The views expressed by the speaker are not necessarily those of AstraZeneca This is an AstraZeneca meeting Date of prep (September/2014) Date of expiry (14/April/2015) AS

2 Adverse events should be reported. Reporting forms and information can be found at events should also be reported to AstraZeneca on Author 00 Month Year Set area descriptor Sub level 1 Sub level 2

3 GLP-1Receptor Agonists and SGLT-2 Inhibitors Debbie Hicks MSc, BA, RGN, NMP, DN Cert, PWT Cert Nurse Consultant Diabetes Barnet, Enfield & Haringey Mental Health Trust

4 Declaration of Interest This presentation has been sponsored by an educational grant from AstraZeneca. The speaker has received payment for articles, presentations and involvement on advisory boards for all the major pharmaceutical companies who support diabetes

5 Presentation Content 1. Current challenges in the management of T2DM 2. Glucagon-Like-Peptide 1 Receptor Agonist What is it? How does it work? Where does it fit in the treatment algorithm for T2DM? 3. Sodium Glucose Co-Transporter 2 Inhibitors What is it? How does it work? Where does it fit into the treatment algorithm for T2DM? 4. Case Studies

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8 What treatments do we have for T2DM? SGLT2 inhibitor Inhibits glucose re-absorption in the kidneys Metformin Decreases hepatic glucose production and increases glucose uptake GLP-1 receptor agonist Improves glucosedependent insulin secretion, suppresses glucagon secretion, slows gastric emptying Pioglitazone Increases insulin sensitivity and glucose uptake in skeletal muscle. Decrease lipolysis in adipose tissue and decrease hepatic glucose output Insulin Increases glucose uptake in skeletal muscle Sulphonylureas and meglitinides Increase insulin secretion from pancreatic β-cells Acarbose Delay intestinal carbohydrate absorption DPP-4 inhibitors Prolong GLP-1 action, stimulate insulin secretion, suppress glucagon release

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11 Incretin Mimetics Glucagon Like Peptides Meal Muscle GIP Increased insulin (beta cells) Glucose dependent Adipose tissue Peripheral glucose uptake Gut GLP-1 Glucose dependent Decreased glucagon (alpha cells) Liver Physiological glucose control Glucose production

12 GLP-1 Agonist GLP-1 agonists (including exenatide once weekly) mimic the effect of incretin hormones released by gut cells in response to food intake, promoting pancreatic islet activity. They are not orally available and must be injected. 4 main actions: Decrease glucagon production reduces hepatic glucose output Increase insulin production allowing peripheral glucose uptake Delays gastric emptying Promotes satiety Secondary benefit of weight loss GLP-1 Agonist products are not licensed for weight loss

13 GLP-1 Agonists Exenatide twice daily (Byetta) Liraglutide once daily (Victoza) Lixisenatide once daily (Lyxumia) Exenatide once weekly (Bydureon)

14 Case study Mick, 53 yrs old, had T2DM for 8 years Current diabetes medications: Metformin 1g BD Gliclazide 160mgs BD Sitagliptin 100mgs OD Recent HbA1c 72 mmols/mol (8.7%), egfr 58 Weight 121 kgs BMI 37 kg/m 2 Works as a window cleaner Drives throughout the day Becoming more symptomatic No history of Pancreatitis (case studies are for illustrative purposes only and the individual patient response may vary)

15 Patient concerns Busy, 6 days a week Doesn t want to inject Worried about his driving licence Doesn t want to put on any more weight Has heard about hypo s can t afford to have one of those when he s up a ladder! Falls asleep as soon as he sits down Doesn t want to monitor his blood glucose levels as problematic whilst at work (case studies are for illustrative purposes only and the individual patient response may vary)

16 HCP concerns Current regimen isn t working Increased risk of long term complications Don t want to risk hypo s due to driving and working at heights Don t want to increase BMI (case studies are for illustrative purposes only and the individual patient response may vary)

17 Agreed care plan Mick is willing to try Bydureon and has decided to do this on Sundays (his day off) Mick is aware that he will not have to inform the DVLA so licence not at risk To allay his fears current dose of Gliclazide reduced to 80 mgs BD, although Mick is aware that Bydureon alone will help not increase the risk of hypos. Bydureon will reduce HbA1C with the secondary benefit of weight loss ( Bydureon is not a weight loss product) (case studies are for illustrative purposes only and the individual patient response may vary)

18 Adverse reactions The most frequent adverse drug reactions ( 5% of patients treated with exenatide QW) were mainly gastrointestinal related (nausea, vomiting, diarrhoea and constipation) In addition, injection-site reactions (pruritus, nodules, erythema), hypoglycaemia (with a SU) and headache occurred Most adverse reactions associated with exenatide QW were mild to moderate in intensity Frequency of adverse reactions with exenatide QW: Incidence of 1% in clinical trials (total N=592; patients on SU n=135) System organ class/adverse reaction terms Very common ( 1/10) Common (1/100 to <1/10) Metabolism and nutrition disorders Hypoglycaemia* [with a SU] Decreased appetite* Nervous system disorders Gastrointestinal disorders General disorders and administration-site conditions Constipation Diarrhoea Nausea* Vomiting* Injection-site pruritus Dizziness* Headache* *Frequency of reactions was the same in the exenatide BID treatment group. BID, twice daily; QW, once weekly; SU, sulphonylurea. BYDUREON. Summary of Product Characteristics. Abdominal distension Abdominal pain* Dyspepsia* Eructation Flatulence* Gastro-oesophageal reflux* Fatigue* Injection-site erythema Injection-site rash Somnolence

19 Conclusion Bydureon is well received by those patients who want the least disruption to their lifestyle Bydureon is well received by patients who want to reduce their HbA1c without increasing their waistline Bydureon is not indicated for weight loss

20 Sodium Glucose Co-Transporters (SGLT-2 Inhibitors)

21 SGLT-2 Inhibitors Dapagliflozin launched in 2012 Canagliflozin launched in 2014 Empagliflozin launched in 2014

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36 Case study 2. Female 46 yrs Diagnosed 2010 Started on Metformin, titrated to 1g BD Started on Pioglitazone, titrated to 45mg OD Poor glycaemic control HbA1c 79 mmol/mol What would you do next? (case studies are for illustrative purposes only and the individual patient response may vary)

37 What actually happened Referred to Intermediate Diabetes Service, Oct 2013 Weight 96 kgs worried about next step due to weight gain Pioglitazone replaced with Dapagliflozin 10 mgs OD After 3/12, HbA1c 58, Weight 90 kgs After 3/12, HbA1c 51, weight 86 kgs, discharged back to GP April No reported side effects (case studies are for illustrative purposes only and the individual patient response may vary) Dapagliflozin is not indicated for weight loss

38 Case study 3. Female 52 yrs, Agrophobic poor social circumstances Weight at diagnosis 90kgs Diagnosed 2008 initially treated with Metformin the escalated through oral options poor effect. Weight 102 kgs Tried GLP-1 RA with oral medication poor effect. Weight 98kgs Tried addition of basal insulin to GLP-1 RA poor effect HbA1c 119kgs referred to Intermediate Diabetes Service Sept 2013 So what next? (case studies are for illustrative purposes only and the individual patient response may vary)

39 What actually happened Referred to Intermediate Diabetes Service Sept 2013 Treatment changed GLP-1 RA + basal insulin + Gliclazide stopped Biphasic insulin BD (44/42) introduced to Metformin SR 1g BD After 3/12 HbA1c reduced to 109 mmols/mol Dapagliflozin 10mgs added after 3/12 HbA1c 78 mmols/mol Weight not measured as yet (case studies are for illustrative purposes only and the individual patient response may vary)

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41 Summary The management of T2DM is highly complex, obesity is often an underlying problem SUCCESS depends on the individual with T2DM being engaged and motivated not an easy task for the rest of their life!

42 Thank you

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