glp-1 receptor agonists and sglt-2 inhibitors debbie hicks · case study . mick, 53 yrs old, had...
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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
GLP-1 Receptor Agonists and SGLT-2 Inhibitors
Debbie Hicks
Date of prep (September/2014)
Date of expiry (14/April/2015) AS 240914
Set area descriptor | Sub level 1 | Sub level 2 Author | 00 Month Year
Adverse events should be reported. Reporting forms and information can be
found at www.mhra.gov.uk/yellowcard.Adverse
events should also be reported to AstraZeneca on 08007830033
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
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
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
Insulin Increases glucose uptake in skeletal muscle
GLP-1 receptor agonist Improves glucose- dependent insulin secretion, suppresses glucagon secretion, slows gastric emptying
DPP-4 inhibitors Prolong GLP-1 action, stimulate insulin secretion, suppress glucagon release
Pioglitazone Increases insulin sensitivity and glucose uptake in skeletal muscle. Decrease lipolysis in adipose tissue and decrease hepatic glucose output
Metformin Decreases hepatic glucose production and increases glucose uptake
Sulphonylureas and meglitinides Increase insulin secretion from pancreatic β-cells
Acarbose Delay intestinal carbohydrate absorption
What treatments do we have for T2DM? SGLT2 inhibitor Inhibits glucose re-absorption in the kidneys
Decreased glucagon (alpha cells)
Increased insulin (beta cells)
Liver
Muscle
Adipose tissue
Incretin Mimetics – Glucagon Like Peptides
Peripheral glucose uptake
Glucose production
GIP
GLP-1 Glucose dependent
Glucose dependent
Meal
Physiological glucose control
Gut
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
GLP-1 Agonists
Exenatide – twice daily (Byetta)
Liraglutide – once daily (Victoza)
Lixisenatide – once daily (Lyxumia)
Exenatide once weekly (Bydureon)
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/m2
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)
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)
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)
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)
•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 Dizziness* Headache*
Gastrointestinal disorders Constipation Diarrhoea Nausea* Vomiting*
Abdominal distension Abdominal pain* Dyspepsia* Eructation Flatulence* Gastro-oesophageal reflux*
General disorders and administration-site conditions
Injection-site pruritus Fatigue* Injection-site erythema Injection-site rash Somnolence
*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.
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
Sodium Glucose Co-Transporters (SGLT-2 Inhibitors)
SGLT-2 Inhibitors
Dapagliflozin – launched in 2012
Canagliflozin – launched in 2014
Empagliflozin – launched in 2014
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)
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 2014. 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
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)
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)
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!
Thank you
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