glp-1 receptor agonists and sglt-2 inhibitors debbie hicks · case study . mick, 53 yrs old, had...

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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

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found at www.mhra.gov.uk/yellowcard.Adverse

events should also be reported to AstraZeneca on 08007830033

http://www.mhra.gov.uk/yellowcard.Adverse

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


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


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)


•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?


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?


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

glp-1 receptor agonists and sglt-2 inhibitors debbie hicks · case study . mick, 53 yrs old, had...

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