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Oral Treatments for Type 2 Diabetes


Oral Treatments for Type 2 Diabetes Prescribing Support Pharmacist Glucose Homeostasis Glucose Homeostasis See NHSGGC guidelines on monitoring of blood glucose for ... – PowerPoint PPT presentation

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Title: Oral Treatments for Type 2 Diabetes

Oral Treatments for Type 2 Diabetes
  • Prescribing Support Pharmacist

Learning Outcomes
  • Recognise the different oral agents used in
    controlling blood glucose levels
  • Describe the pharmacological effects of the
  • Explain the side effects of the agents
  • Understand the rationale for clinical guidelines

Black Triangle?
  • ?Identifies preparations in the BNF that require
    additional monitoring by the European Medicines
  • All suspected adverse reactions should be
    reported by the yellow card scheme to the
    Commission on Human Medicines
  • www.yellowcard.gov.uk

Type 2 Diabetes is a ProgressiveDisease UKPDS1
Cross-sectional median values
  • Conventional Treatment (n1138)
  • Intensive Treatment (n2729)
  • 9
  • 8
  • ADA action
  • suggested
  • Median A1C ()
  • 7
  • ADA target
  • 6
  • 0
  • 0
  • 3
  • 6
  • 9
  • 12
  • 15
  • Time From Randomisation (years)

  • 3 Add statin
  • 4 Add metformin
  • 2 Control BP
  • 5 consider tight glucose control
  • 1 Lifestyle (exercise, diet, stop smoking)
  • Dont turn the hand around
  • Lets give our diabetic patients a hand!

Where does controlling Blood Glucose fit into the
  • No arguments in favour of poor BG control
  • Importantly,data from RCTs, found no benefit and
    possible harm from tight BG control -targetlt
  • Achieving good BG control, while addressing
    lifestyle, BP, and lipids will prevent more
    complications, than a narrower approach focused
    on intensive BG control
  • Individualise treatment
  • Agree targets with patient

Why is good glycaemic control important?
  • Microvascular Complications
  • Macrovascular Complications
  • Stroke
  • 2- to 4-fold increase in cardiovascular mortality
    and stroke4,5
  • Diabetic Retinopathy
  • Leading cause of blindness in
  • working-age adults1
  • Diabetic Nephropathy Leading cause of
  • end-stage renal disease2
  • Heart Disease6
  • Diabetic Neuropathy
  • Leading cause of nontraumatic lower extremity
  • Peripheral
  • Vascular Disease6
  • All references last accessed April 2012 1. IDF.
    Fact Sheet Diabetes and Eye Disease. Available
    at http//www.idf.org/node/1186?unodeC1CCADE9-4A
    03-4D17-A662-155B3ED59FDB. 2. The Renal
    Association. UK Renal Registry. Twelfth Annual
    Report. December 2009. Available at
    http//www.renalreg.com/Reports/2009.html. 3.
    Dang, CN., Boulton, AJ., International Journal of
    Lower Extremity Wounds. 2003 2(1)4-12. 4.
    Jeerakathil, T., et al. Stroke.
    200738(6)1739-43. 5. Kaul, S., et al.
    Circulation. 20101211868-77. 6. IDF. Fact
    sheet Diabetes and Cardiovascular Disease (CVD).
    Available at http//www.idf.org/fact-sheets/diabe


Glucose Homeostasis
Biguanides - Metformin
  • 1st choice in obese patients - helps weight loss
    and rarely causes hypoglycaemia, as it does not
    stimulate insulin secretion
  • Side-effects GI upset (anorexia, nausea,
    vomiting, diarrhoea), B12 malabsorption, and very
    rarely lactic acidosis
  • Renal impairment dose should be reduced
  • Can be used alone or in combination with any
    other oral hypoglycaemic agent or insulin

  • If HbA1c remains at or below 53mmol/mol on
    Metformin continue to review the patient 6
  • Metformin has been shown to reduce CVD events
  • (UK Prospective Diabetes Study
  • Has favourable effects on lipid metabolism it
    reduces total cholesterol, LDL cholesterol and
    triglyceride levels

When to intensify treatment?
  • If HbA1c is still lt53mmol/mol or if
    individualised target is not met
  • The addition of a second oral agent is likely to
    improve HbA1c by no more than 9.0 16mmol/mol
  • Withdraw treatment after 6 months if HbA1c has
    decreased by less than 6mmol/mol

Options for second line drug therapy
  • Sulphonylurea
  • Pioglitazone
  • Gliptin (DPP-4 inhibitor)
  • SGLT-2 ?
  • Consider individual patient factors and


  • Side-effects GI, weight gain, hypoglycaemia
  • Caution in hepatic/renal impairment (increased
    chance of hypos). If hepatic/renal impairment is
    severe - Avoid
  • Contra-indicated Pregnancy, breastfeeding,
    acute porphyria, ketoacidosis

  • Pros
  • Confidence and experience in using
  • Cheap (generic 6 per month)
  • Effective (mean 1 reduction HbA1c)
  • Minimal responder variability
  • Cons
  • Significant hypoglycaemia risk BGM may be
    appropriate for 1st three months
  • Weight gain
  • Poor durability

Thiazolidinediones (Glitazones)
  • Side-effects
  • GI, weight gain, hypoglycaemia (rarely). It is
    associated with fluid retention and has
    precipitated heart failure and pulmonary oedema
    in patients at risk
  • Cautions
  • Monitor liver function Check LFTs before use
    and periodically thereafter
  • Contra-indications
  • Hepatic impairment
  • Pregnancy and breast-feeding
  • Previous or active bladder cancer

Pioglitazone and Heart Failure
  • PROactive Study
  • Cardiac failure risk 39 higher in Pioglitazone
    group compared to placebo. (5.7 v 4.1)
  • Of those with serious heart failure mortality due
    to heart failure similar in both groups
  • And all cause mortality lower in Pio group (26.8
    v 34.3)

Pioglitazone bladder cancer
  • Risk of Bladder Cancer July 2011
  • The European Medicines Agency has advised that
    there is a small increased risk of bladder cancer
    associated with pioglitazone use
  • However, in patients who respond adequately to
    treatment, the benefits of pioglitazone continue
    to outweigh the risks

Pioglitazone and bone fractures
  • 39 increased incidence of fractures in men and
    women on TZDs.
  • Increased incidence in all women and in men gt 50

DPP-4 inhibitors (Gliptins)
  • DPP-4 inhibitors work by blocking the action of
    DPP-4, an enzyme which destroys the hormone

DPP-4 Inhibitors (Gliptins)
  • Preferred List
  • Sitagliptin (Januvia) 1st choice
  • Linagliptin (Trajenta) ?
  • Total Formulary
  • Saxagliptin (Onglyza)
  • Vildagliptin (Galvus)
  • Alogliptin (Vipidia) ?

DPP-4 inhibitors (Gliptins)
  • Monotherapy only if metformin or SU
    contraindicated or not tolerated
  • Combination with a sulphonylurea is restricted to
    patients in whom metformin is contraindicated or
    not tolerated.
  • Combination with both metformin and a
    sulphonylurea (i.e triple therapy) restricted to
    patients who are inadequately controlled on max
    tolerated doses of metformin and sulphonylurea.
  • NB dose of concomitant Sulphonylurea or insulin
    may need to be reduced

DPP-4 inhibitors (Gliptins)
  • Pros
  • Very low hypo risk
  • Weight neutral
  • Low side-effect profile
  • Cons
  • Expensive (around 30 per month)
  • Less effective (mean 1 reduction HbA1c)
  • Responder variability
  • No long term safety information

DPP-4 Inhibitors (Gliptins)
  • Side-effects-GI disturbance, peripheral oedema
  • Caution elderly
  • Contra-Indications Ketoacidosis, pregnancy,
    breast feeding. Doses may need adjusted in renal
    or hepatic impairment

SGLT-2 inhibitors
SGLT-2 Inhibitors
  • All on NHSGGC total formulary -
  • Canagliflozin (Ivokana ) ?
  • Dapagliflozin (Forxiga ) ?
  • Empagliflozin (Jardiance) ?

SGLT2 Inhibitors
  • NOT recommended for monotherapy
  • Restricted to initiation by clinicians
    experienced in the management of diabetes for the
  • Side effects constipation, genital infection,
    nausea, polyuria, thirst, urinary frequency, UTI

SGLT2 Inhibitors
  • Pros
  • Weight loss
  • Very low hypo rate
  • Effective at all stages of diabetes
  • Cons
  • High cost
  • Urinary tract infections
  • Genital thrush
  • No long term safety information
  • Not licensed in eGFR lt60mls/min

SGLT-2 inhibitorsHepatic and Renal Function
MHRA advice on SGLT-2 inhibitors and Ketoacidosis
  • SGLT2 inhibitors are licensed for use in adults
    with type 2 diabetes to improve glycaemic
  • Serious, life-threatening, and fatal cases of DKA
    have been reported in patients taking an SGLT2

MHRA advice on SGLT-2 inhibitors and Ketoacidosis
  • Advice for HCPs
  • Educate patients on symptoms of DKA and what to
    do if experiencing symptoms.
  • Test for raised ketones in patients with
    ketoacidosis symptoms, even if plasma glucose
    levels are near-normal.
  • Report suspected side effects to SGLT2 inhibitors
    or any other medicines on a Yellow Card

Two Infrequently used Oral Type 2 Hypoglycaemic
  • Alpha-Glucosidase Inhibitors (Acarbose)
  • Meglitinides (Repaglinide Nateglinide)

Acarbose (Glucobay)
  • The largest evidence base for the alpha
    glucosidase inhibitors is with Acarbose and its
    in the GGC Formulary restricted to patients who
    cant tolerate Metformin
  • Acarbose works by slowing down the absorption of
    starchy foods from the intestine. This means that
    blood glucose levels rise more slowly after
    meals. Acarbose should always be chewed with the
    first mouthful of food or swallowed whole with a
    little liquid immediately before the meal.
  • Main side-effects are flatulence and diarrhoea

Meglitinides (Repaglinide Nateglinide)
  • Like the sulphonylureas, these stimulate the
    cells in the pancreas to produce more insulin.
    However, unlike the sulphonylureas, they work
    very quickly but only last for a short time and
    are given within half an hour before each meal.
  • If a meal is missed, the dose must be omitted.
    These tablets are taken up to three times daily.
  • Not in GGC Formulary

Depends entirely on your patient...
  • What next?

  • Consider adding a third oral medication?
  • Only likely to be effective if HbA1c is lt 86
  • Consider adding a injectable GPL1-agonist?
  • Only if BMI gt30kg/m2
  • Consider starting insulin therapy?
  • Can cause weight gain and requires more intensive

Glucagon-Like Peptide-1 (GLP-1) analogues
  • This type of medication works by increasing the
    levels of hormones called incretins. These
    hormones help the body produce more insulin only
    when needed and reduce the amount of glucose
    being produced by the liver when its not needed.
    They reduce the rate at which the stomach digests
    food and empties, and can also reduce appetite.

Glucagon-Like Peptide-1 (GLP-1) analogues
  • 5 GLP-1 analogues which have been approved by SMC
    for use in NHSScotland -
  • Exenatide (Byetta) - Twice daily s/c
  • Exenatide (Bydureon) - Once weekly s/c
  • Liraglutide (Victoza) - Once daily s/c
  • Lixisenatide (Lyxumia) Once daily s/c
  • Albiglutide (Eperzan) Once weekly s/c
  • Dulaglutide (Trulicity) Once weekly s/c

The Introduction of Insulin
  • If there is suboptimal control with two (or
    three) oral hypoglycaemic agents or if dual
    therapy is contraindicated then insulin should be
    introduced with one oral hypoglycaemic agent,
    preferably metformin

Taken from GGC Diabetes Guideline available from
Taken from GGC Diabetes Guideline available from
  • GGC Formulary
  • http//www.ggcprescribing.org.uk/
  • Clinical guidelines
  • http//www.staffnet.ggc.scot.nhs.uk
  • SMC Advice
  • https//www.scottishmedicines.org.uk/SMC_Advice/Ad

Driving and Type 2 Diabetes
  • For further information see
  • NHSGGC Self-monitoring of Blood Glucose
  • or
  • https//www.gov.uk/diabetes-driving

  • GGC Diabetes Guideline
  • Available at http//www.ggcprescribing.org.uk
  • SIGN 116 March 2010
  • Available at www.sign.ac.uk
  • Nice NG28 Dec 2015
  • Available at www.nice.org.uk
  • BNF 69 Sept 2015
  • Available at www.bnf.org
  • The Scottish Medicines Consortium
  • Available at www. http//www.scottishmedicines.o
  • Diabetes and Driving
  • Available at https//www.gov.uk/diabetes-driving

Case 1
  • Mr Smith is a 52 year old man who drives long
    distances in lorries for a living. Mr Smith is a
    smoker and was diagnosed with Type 2 diabetes 5
    years ago.
  • HbA1c last week was 70mmol/mol
  • Current medication
  • Metformin 500mg at a dose of 1g twice daily
  • Do you want to change or add to Mr Smiths
    medication regimen?
  • Discuss the options available and what
    medications you might add to his current regimen.

What to do with Mr Smith
  • Move to second line based on HbA1c being
  • Gliclazide not selected based on occupational
    hazards with hypoglycaemia risk
  • Suitable options remaining
  • Glitazone
  • Gliptin
  • SGLT-2

Case 2
  • Mrs Mackie is a 78 year old lady with Type 2
    diabetes. She has been
  • prescribed her current medications for the last 7
    years and her HbA1c
  • has been stable under 53mmol/mol.
  • Current Medication
  • Metformin 1000mg twice daily
  • Gliclazide 80mg twice daily
  • Pioglitazone 30mg daily
  • Mrs Mackie has developed osteoporosis and has
    also suffered from an MI with resulting Heart
    Failure NYHA Class 2 in the past 3 years.
  • You are carrying out her annual diabetes review.
    Are there any
  • considerations you may need to make when
    reviewing her current
  • medication regimen?

What to do with Mrs Mackie
  • Pioglitazone
  • Contra-indicated in Heart Failure
  • Caution in osteoporosis as can increase the risk
    of fractures
  • Stop Pioglitazone
  • Consider commencing Gliptin or SGLT2

Case 3
  • Miss Carter is a 84 year old lady who has had
    Type 2 diabetes since
  • she was 72.
  • Current Medication
  • Metformin 1g twice daily
  • Gliclazide 40mg twice daily
  • Empagliflozin 25mg once daily
  • Renal Function is being monitored by the practice
    nurse and has noted to be falling. Most recently
    it is 53ml/min
  • What else would you want to know?
  • What do you do?

What to do with Miss Carter
  • Consider reduced renal function
  • If falling persistently below 60ml/min reduce
    dose to 10mg once daily. Stop if eGFR reduces
    below 45ml/min
  • Review patients HbA1c does she need all this
    medication for type 2 diabetes, often patients
    lose weight as they get older and more frail
    therefore her HbA1c may be reducing based on
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