Type 2 Diabetes - Referral Criteria to Specialist Services

Transcription

1 Diabetes Pathway Contact Tel: Fax: Mon-Fri 9.00am-5.00pm Consultants Produced by West Hampshire Community Diabetes Service October 2015 Adapted from Leicester Diabetes Guidelines 2013

2 Type 2 Diabetes - Referral Criteria to Specialist Services Secondary Care referral criteria 1. Antenatal 2. Ophthalmology 3. Insulin pumps 4. Foot clinic 5. Specialist joint renal clinic (GFR <30) 6. Bariatric Service Same day secondary care referrals Newly diagnosed Children with Diabetes - refer to Paediatric Services. All children suspected of diabetes need to be referred to secondary care urgently Newly diagnosed Type 1 Diabetes urgent in those who present with ketonuria and/or vomiting Patients with infected, necrotic or gangrenous foot ulceration or suspected Charcot Foot Sudden loss of vision contact local eye casualty Secondary Care Services: urgent referrals Hospital Emergency DSNs Secretary/Admin Winchester RHCH Basingstoke NHH McGill ward / AAU via switchboard x5502 On call medical doctor bleep 131 Fax: Fax: Southampton UHS EMAU x3761 bleep Fax: Salisbury Bournemouth 9.00am-7.00pm Out of Hours: bleep medical reg 1361 Switchboard ask for Medical admissions Fax: Paediatric services Salisbury Hospital Southampton x6893 Winchester Portsmouth Multidisciplinary Foot Care services Basingstoke NHH Mon pm Winchester RHCH Weds am Andover War Memorial Hospital Royal Bournemouth Hospital Solent Health Podiatry (Portsmouth & Southampton) Salisbury Mon and Tues am Antenatal clinics Florence Portal, RHCH. Winchester Tues am Basingstoke NHH Thurs pm Southampton General Hospital Salisbury Tues am Royal Bournemouth Hospital Fri am

3 Primary care referral criteria to West Hampshire Community Diabetes Service Patient Education Type 1 Type 2 Suboptimal glycaemic control, despite titration of medication according to NICE guidance Patients with complications: 1. Stage 3b CKD 2. Diabetic Retinopathy* (active ophthalmology FU) 3. Painful Diabetic Neuropathy 4. Previous Amputation 5. Active foot ulceration* 6. Active macrovascular disease (MI/unstable angina/cva/tia within the last year) 7. Other diabetic related complications (*with no access to active secondary care specialist service) Others where specialist advice may be considered Referral to West Hampshire Community Diabetes Service (WHCDS) Recurrent hypoglycaemia and impaired hypo-awareness Poor glycaemic control despite intensive management Persistent hypertension and/or hyperlipidaemia despite intensive management as per guidelines Painful neuropathy not responding to treatment (refer to Specialist Care) People with Type 1 Diabetes with previous failure to attend but now receptive to specialist referral Patients CKD 3 for optimisation of glucose, BP and lipids if control suboptimal Patients for type 1 carbohydrate counting education Patients in whom insulin pump therapy is being considered (refer for assessment) Emergency Eye Departments Southampton UHS Salisbury ext 4327 Basingstoke NHH Royal Bournemouth Hospital Portsmouth Hampshire Eye Screening Services Southampton Diabetic Eye Screening Service (Southampton and Isle of Wight) Royal South Hants Hospital Brintons Terrace Southampton SO14 0YG Salisbury & North Hampshire Diabetic Eye Screening Programme Block 8 Salisbury NHS Foundation Trust Salisbury District Hospital Odstock Road Salisbury SP2 8BJ r.screening1@nhs.net Portsmouth and South East Hampshire Diabetic Eye Screening Service Patient Management Centre 27 Guildhall Walk Portsmouth PO1 2RY Tel: CUK.drgpu@nhs.net

4 Type 2 Diabetes - Diagnosis and screening National Service Framework for Diabetes - Standard 2 Diagnosis of Type 2 diabetes can be made using HbA1c in those who are asymptomatic. It should not be used for diagnosis in children, pregnancy and those who are acutely ill or who have abnormal haemoglobins, anaemia and altered red blood cell lifespan. Diabetes is often missed in the elderly Glycosuria on its own does not confirm diabetes Whom to test At least half of people with Type 2 diabetes are asymptomatic Remember to test for diabetes if patients present with the following symptoms: Excess thirst Polyuria (especially if nocturia) Weight loss Urinary incontinence Tiredness Pruritis Vulvae / recurrent candidiasis Recurrent infections / abscesses Balanitis Blurred Vision / changes in visual acuity Erectile Dysfunction Pain / Numbness / foot ulcers Non specific or unexplained symptoms Predetermined risk of diabetes Coronary Heart Disease Women who have had Gestational Diabetes (screen at 6 weeks and one year post-partum, and then yearly) Those known to have impaired glucose tolerance, HbA1c % (42 47mmols/mol) or oral glucose tolerance test 2-hour value between 7.8mmol/l and 11.1 mmol/l impaired glucose regulation (IGR) or fasting glucose mmol/l(Impaired fasting glucose IFG) How to test An HbA1c of 48mmol/l (6.5%) is diagnostic of diabetes in most situations. It can be used to diagnose diabetes in asymptomatic patients. It should not be used in certain patient groups including children, pregnancy, suspected type 1 diabetes and acute illness. Measurement can be misleading in patients with haemoglobinopathies, anaemia or renal failure. Finger prick capillary results can not be used to diagnose diabetes It is very important to identify diabetes as early as possible: 50% of newly presenting people with Type 2 diabetes already have 1 or more complications at diagnosis (1) High risk for diabetes White European people aged over 40 and people from Black, Asian and minority ethnic groups aged over 25 with first degree relative with diabetes BMI of (i.e. are overweight) and who have a sedentary lifestyle >23 in South Asian people BMI >30 Women with polycystic ovary syndrome Cerebrovascular disease, peripheral vascular disease or hypertension/ hyperlipidaemia Patients on prolonged steroid therapy Patients on atypical anti-psychotic drugs (1) UKPDS Group. UK Prospective Diabetes Study 6. Complications in newly diagnosed Type 2 diabetic patients and their association with different clinical and biochemical risk factors. Diabetes Research. 1990;13:1-11 (2) World Health Organisation. Report of a WHO Consultation 1999 (3) The Expert Committee on the diagnosis and Classification of Diabetes Mellitus

5 Type 2 Diabetes - Glycaemic management National Service Framework - Standard 4 Treatment decision tree for early insulin initiation Principles of Treatment Offer structured education The National Recommended Criteria from DoH on Structured Education 2004) to include diet/lifestyle advice to everyone. Usually wait 6-12 weeks before glucose lowering agents are introduced. However: Introduce oral hypoglycaemic agents early if fasting plasma glucose >15mmol/l and symptomatic. In patients with suspected type 1 diabetes or very raised glucose levels, (HbA1c>100mmols/mol) and symptomatic, Blood glucose monitoring is recommended and consider early treatment with insulin. In these patients ensure they are shown how to monitor their own diabetes, and know what to do if results do not fall in the target range. Consider referral to Specialist if type 1 Diabetes is suspected See flow chart. Regular monitoring will identify the need to actively titrate treatment. Measure HbA1c every 2-6 months. Target HbA1c 48mmol/mol/6.5% in newly diagnosed Type 2 diabetes and those on up to two oral hypoglycaemic agents unless individual target more appropriate or at risk of hypoglycaemia. Involve the person in discussions about individual HbA1c target. In South Asian people BMI underestimates adiposity. Waist measurements need to be considered. Range for healthy weight is BMI in South Asian people. Symptoms of hyperglycaemia and a diagnostic blood glucose (random 11.1 mmol/l) YES Is the patient ill (vomiting, semiconscious or clinically dehydrated)? NO Does the urine test show moderate/heavy ketonuria? NO Are one or more of the following present? Severe osmotic symptoms (nocturia x 3-4) Short history (weeks) Marked weight loss (irrespective of absolute weight) A first degree relative with Type 1 Diabetes A personal history of autoimmune disease NO Is the patient under 30 years of age? NO There is no immediate need for insulin. Give dietary advice on healthy eating. Provide regular review. YES YES YES YES Arrange direct admission to hospital Very likely to need insulin. Discuss with specialist team within 24 hours. Two or more are a strong indication for insulin First degree relative on diet or tablets consider Maturity Onset Diabetes of the Young (MODY)

6 Type 2 Diabetes - Diet Aims of dietary management: Achieve normal glycaemia Reduce and or/maintain weight and waist measurements within healthy ranges Manage dyslipidaemia Manage hypertension Manage hypoglycaemia Dietary basics: 1. Regular, well balanced meals (three meals/day) based on the Eatwell Plate. Snacks are not necessary unless treating or preventing hypoglycaemia. Portion sizes should be appropriate to the individual and their activity level. A useful guide is to use the clenched fist as a standard carbohydrate portion, the palm of the hand for the protein portion and as many vegetables as could be fitted into two cupped hands. 2. Reduce saturated fat intake by changing type of fat from saturated to unsaturated, preferably monounsaturated (olive or rapeseed based spreads and oils) and removing visible fat from food e.g. chicken skin, bacon rind. Fat is the most energy dense nutrient and should be reduced if weight loss is desired. 3. Eat at least 5 portions each day of fruit and vegetables, a portion is roughly what can be held in the hand e.g one apple, 6 strawberries, 2 apricots. Eating vegetables more than fruit is preferable for weight loss or improved blood sugar control and only one portion of fruit at a time due to high natural sugar content. Temperate/home-grown fruits (e.g. apples, pears, plums, berries) are preferable to tropical varieties (e.g. bananas, grapes, mango) as they have a lower glycaemic index. Including beans or lentils will increase fibre content and reduce the glycaemic effect of meals. 4. Choose low glycaemic index carbohydrates e.g. those with wholegrains, oat-based cereals and breads, as they cause a more gradual and sustained rise in blood sugar levels 5. Avoid sugary drinks e.g. regular varieties of cordials, fizzy drinks or adding sugar to hot drinks. Low sugar varieties are available. 6. Reducing salt and salty foods will help control hypertension. Foods labelled as less than 0.3g or salt or 0.1g sodium per 100g are considered to be low salt. Choose alternative flavourings for foods e.g. curry, pepper, lemon rather than adding salt. Maximum daily intake 6g of salt or less is recommended. 7. Eat 1-2 portions of oily fish per week for the benefit of omega-3 fats 8. Diabetic foods and drinks have no special benefit and are not necessary in a healthy diabetic diet 9. All carbohydrates will affect blood glucose levels. Educating people with diabetes about carbohydrate contents can help them achieve consistent carbohydrate intake for stable blood sugars or to be able to adjust the doses of their rapid acting insulin if on basalbolus insulin regimens 10. Regular moderate activity each day will reduce insulin resistance and reduce weight BMI relates to an individual s weight in relation to their height. For most adults, an ideal BMI is in the range. BMI is not a useful measure in people of muscular build e.g. military personnel, sports people. BMI Classification <18.5 Underweight Desirable Overweight Obese 40+ Morbidly obese Waist circumference is most useful in people with BMI It provides an additional measure and indicator of risk. Waist circumference measurement for men and women at which there is an increased relative risk is: Increased risk Substantially increased risk Men >=94 cm (37 ) >=102 cm (40 ) Women >=80 cm (31.5 ) >=88 cm (34.5 )

7 Type 2 Diabetes - Monitoring Glycaemic control National Service Framework for Diabetes- Standard 4 Key principles of practice 95% of the care people with diabetes receive is self-care and all patients should have access to high quality structured education programmes The ability to monitor their own glucose level gives people with diabetes the feedback they need in order to learn how to manage their condition optimally. Monitoring should be based on the individual s clinical needs and in the context of diabetes education and self management. People should receive appropriate training in the technique and the actioning of the results. The frequency of testing will be different for different people and will change with their circumstances. Any guidelines can only be used as a framework and then adapted to meet individual needs. People may move between different methods of monitoring dependent on their needs at that time. Equipment used for monitoring should follow local guidelines and policies Nice ref (1) MeREC review (2) Reference HbA1c (Glycated haemoglobin) At least once a year, your doctor should check your long-term diabetes control by taking a blood sample from your arm. HbA1c The most common test is the HbA1c test, which indicates your blood glucose levels for the previous two to three months. The HbA1c measures the amount of glucose that is being carried by the red blood cells in the body. Ref Diabetes UK Haemoglobin A1c Ideal targets are <53mmol/mol (7.0%) in Type 1 Diabetes and <48mmol/mol (6.5%) in newly diagnosed and short duration Type 2 Diabetes. Although we need to strive for these levels, targets should be set with the individual patient. Should not be measured more frequently than two monthly, except in pregnancy, and should be measured at least 6-12 monthly. Avoid pursuing highly intensive management to levels of <48mmol/ mol (6.5%). HbA1c levels between 6.5% (48mmol/mol) to 48mmol/mol (6.5%) are recommended by NICE (1) a MeREC review (2) states..if appropriate and achievable in an individual, reducing blood glucose to HbA1c levels of around 7.5% would seem optimal based on current evidence. Lower levels may be appropriate for individuals with early disease... NICE note that (1): when setting a target glycated haemoglobin (HbA1c): involve the person in decisions about their individual HbA1c target level, which may be above that of 6.5%(48mmol/mol) set for people with type 2 diabetes in general encourage the person to maintain their individual target unless the resulting side effects (including hypoglycaemia) or their efforts to achieve this impair their quality of life offer therapy (lifestyle and medication) to help achieve and maintain the HbA1c target level inform a person with a higher HbA1c that any reduction in HbA1c towards the agreed target is advantageous to future health HbA1c conversion table HbA1c (new units) (mmol/mol) HbA1c (old units) % A 0.5% difference in HbA1c is equivalent to a difference of about 5.5mmol/ mol, and a 1% difference is equivalent to a difference of about 11mmol/ mol Note that these are rounded equivalents. Patient education All people newly diagnosed with type 2 diabetes (and/or their carer) should be offered referral to a structured education programme. Inform people and their carers that structured education is an integral part of diabetes care. West Hampshire Community Diabetes Service has a range of patient education programmes and workshops. For more details view the People Living with Diabetes Eductation Prospectus at

8 Type 2 Diabetes - Monitoring Glycaemic control National Service Framework for Diabetes- Standard 4 Type 2 Diabetes - Diet & lifestyle management only Self blood glucose monitoring is not recommended as part of routine care if HbA1c is within target but may be useful as an educational tool to understand lifestyle interventions. Urine testing may be adequate provided HbA1c targets are achieved. Measure HbA1c 3 monthly until target is reached, then monitor 6 monthly. If self-monitoring of blood glucose is considered appropriate, possible regime is: A Type 2 Diabetes Oral therapy Re-assess patient needs if not achieving target HbA1c level, or if there is risk of hypoglycaemia which cannot be addressed by using an alternative diabetes treatment. Consider self blood glucose monitoring. Frequency of testing should be agreed with patient and adequate training provided. Some patients benefit from blood testing for short periods of time and then stop or return to urine testing, e.g. when oral medication is changed or adjusted. Continue to measure HbA1c 3-6 monthly. Possible regimes: A B C Type 2 Diabetes Insulin with/ without oral agents Self blood glucose monitoring is recommended. Regular testing is required at initiation and during adjustment of doses. Frequency may be reduced when glycaemic target reached. Increased testing may be required during intercurrent illness and when there is risk of hypoglycaemia. Adequate training must be provided. Those unable to self-monitor blood glucose may find urine testing helpful or may require more frequent HbA1c measurement. HbA1c should be measured 3-6 monthly Possible regimes: B C D Self-monitoring of plasma glucose should be available: to those on insulin treatment to those on oral glucose-lowering medications to provide information on hypoglycaemia to assess changes in glucose control resulting from medications and lifestyle changes to monitor changes during intercurrent illness to ensure safety during activities, including driving Assess at least annually and in a structured way: self-monitoring skills quality and appropriate frequency of testing use made of the results obtained impact on quality of life continued benefit equipment used If self-monitoring is appropriate but blood glucose monitoring is unacceptable to the individual, discuss the use of urine glucose monitoring ref: Type 2 diabetes NICE clinical guideline 87 Typical Self-Monitoring Regimens A Periodic testing to meet needs at that time B 1-2 tests daily, varying times of testing including pre meal and post meal C 4 tests per day x 2 week D 4 tests per day each day E 7 tests per day pre & post meals Pregnancy Gestational Diabetes, type 2 diabetes and type 1 diabetes Will need to monitor both pre meal and 1 hour post meal glucose levels and frequency will depend on treatment Possible regimes: D E Type 1 Diabetes It is recommended that all people with Type 1 Diabetes monitor their blood glucose levels. Self-monitoring may be used to adjust insulin doses prior to mealsmeals (eg basal bolus therapy and carbohydrate counting, pump therapy, during pregnancy) and so frequent daily testing will be required up to 4-7 tests per day. In more stable Type 1 Diabetes less frequent monitoring may be acceptable depending on patients daily routine. Children with Diabetes or their parents may need to do frequent testing and this will be decided between themselves and the specialist paediatric team but could range from 1-7 tests per day. HbA1c should be measured 3-6 monthly in all Type 1 Diabetes Patients. Possible regimes: B C D E Targets for Self-blood glucose monitoring (SBGM) These should be set with the individual patient taking into account age, infirmity, and clinical factors. Recommended targets for the general adult population are: Type 2 diabetes Pre-meals: 4-7 mmol/l 2 hours post prandial: <8.5 mmol/l Type 1 diabetes Pre meal 4-7mmol/l. 2 hours post prandial <9mmol/l Driving recommended >5mmols is safe to drive

9 Type 2 Diabetes - Treatment Algorithm

10 Type 2 Diabetes - Medications Biguanides - Metformin (Metformin is the only available biguanide) Decreases gluconeogenesis and increases peripheral utilisation of glucose. Drug Notes Formulary choice Precautions/ Contra-indications/ Patients with complex disease Metformin Price per month: 1g twice daily 6.32 Sept 2015 Metformin MR Price per month: 2g daily: Sept 2015 Metformin has a cardioprotective effect NICE guidance (CG87): Start metformin treatment in a person who is overweight or obese (tailoring the assessment of body-weight-associated risk according to ethnic group) and whose blood glucose is inadequately controlled by lifestyle interventions (nutrition and exercise) alone. Consider metformin as an option for first-line glucose-lowering therapy for a person who is not overweight. Continue with metformin if blood glucose control remains or becomes inadequate and another oral glucose-lowering medication (usually a sulfonylurea) is added. NICE guidance (PH38): Use clinical judgement on whether (and when) to offer standardrelease metformin to support lifestyle change for people whose HbA1c or fasting plasma glucose blood test results have deteriorated if: this has happened despite their participation in an intensive lifestyle-change programme, or they are unable to participate in an intensive lifestyle-change programme. Consider a trial of extended-absorption metformin tablets where GI tolerability prevents continuation of metformin therapy. (NICE CG87) First choice Second choice (for patients with proven GI intolerance) Actively titrate the dose of metformin (i.e. increase to the maximum tolerated dose). This must be done over several weeks to minimise risk of gastrointestinal (GI) side effects. (NICE CG87). If adding metformin to gliclazide, it may be appropriate to decrease the gliclazide dose in order to titrate the metformin. HbA1c target for patients on metformin plus gliclazide should not be lower than 59mmol/ml. Renal impairment (NICE CG87): Review the dose of metformin if the serum creatinine exceeds 130 micromol/ litre or the estimated glomerular filtration rate (egfr) is below 45 ml/ minute/1.73-m2. Stop the metformin if the serum creatinine exceeds 150 micromol/litre or the egfr is below 30 ml/minute/1.73-m2. Prescribe metformin with caution for those at risk of a sudden deterioration in kidney function and those at risk of egfr falling below 45 ml/ minute/1.73-m2. Liver or cardiac impairment (NICE CG87): The benefits of metformin therapy should be discussed with a person with mild to moderate liver dysfunction or cardiac impairment so that: due consideration can be given to the cardiovascular-protective effects of the drug an informed decision can be made on whether to continue or stop the metformin.

11 Type 2 Diabetes - Medications Sulfonylureas - Gliclazide Augments insulin secretion and consequently is only effective when some residual pancreatic beta-call activity is present. Drug Notes Formulary choice Precautions/ Contra-indications/ Patients with complex disease Gliclazide Price per month (Nov14): 80mg daily- 160mg twice daily Prescribe gliclazide when a sulfonylurea is indicated. NICE guidance (CG87): Consider a sulfonylurea as an option for first-line glucose-lowering therapy if: the person is not overweight the person does not tolerate metformin (or it is contraindicated) or a rapid response to therapy is required because of hyperglycaemic symptoms. Add a sulfonylurea as second-line therapy when blood glucose control remains or becomes inadequate with metformin. First choice Educate the person about the risk of hypoglycaemia, particularly if they have renal impairment. Increase dose every 4-6 weeks to achieve glycaemic target (do not exceed maximum dose). Check blood glucose (finger prick) before each titration to reduce risk of causing hypoglycaemia. HbA1c results of less than 48mmol/ml in patients on gliclazide should prompt a review of therapy due to a risk of symptomatic hypoglycaemia. If adding metformin to gliclazide, it may be appropriate to decrease the gliclazide dose in order to titrate the metformin. HbA1c target for patients on gliclazide plus metformin should not be lower than 59mmol/ml. Gliclazide can cause weight gain (a few kilograms). Advice for drivers: For Group 1 drivers (car/motorcycle) it may be appropriate to monitor blood glucose regularly and at times relevant to driving to enable the detection of hypoglycaemia. Group 2 drivers (bus/lorry) on sulfonylureas are required by law to monitor glucose level at least twice daily and at times relevant to driving. For more information about driving with diabetes see the Government guidance for drivers with diabetes and advice for drivers on the Diabetes UK website. DVLA also has info- see guidance for professionals.

12 Type 2 Diabetes - Medications Gliptins (also known as DPP-4 inhibitors) Inhibit dipeptidylpeptidase-4 to increase insulin secretion and to lower glucagon secretion. Drug Notes Formulary choice Alogliptin rice per month (May15): 6.25mg- 25mg daily Combinations approved for use locally: Dual therapy with metformin, sulfonylurea or pioglitazone. Triple therapy with metformin & pioglitazone. Insulin (with or without metformin). NB there is currently limited data regarding use of alogliptin when used as triple therapy with metformin and a sulphonylurea First choice gliptin for new patients and dose changes Precautions/ Contra-indications/ Patients with complex disease See sitagliptin entry for MHRA warning regarding pancreatitis (applies to all gliptins). No long term safety data available for these agents. Renal impairment (CrCl, SPC): >50ml/min no dose adjustment 30-50ml/min 12.5mg daily <30ml/min 6.25mg daily Sitagliptin Price per month (Nov14): 25mg -100mg daily Licensed in combination with: other glucose lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control. Low risk of hypoglycaemia and are weight neutral. NICE guidance (CG87): Consider adding a gliptin instead of a sulfonylurea as second-line therapy to first-line metformin when control of blood glucose remains or becomes inadequate (HbA1c 48mmol/mol, or other higher level agreed with the individual) if: the person is at significant risk of hypoglycaemia or its consequences (for example, older people and people in certain jobs [for example, those working at heights or with heavy machinery] or people in certain social circumstances [for example, those living alone]), or the person does not tolerate a sulfonylurea or a sulfonylurea is contraindicated. Consider adding a gliptin as second-line therapy to first-line sulfonylurea monotherapy when control of blood glucose remains or becomes inadequate (HbA1c 48mmol/mol, or other higher level agreed with the individual) if: the person does not tolerate metformin, or metformin is contraindicated. Consider adding a gliptin as third-line therapy to first-line metformin and a second-line sulfonylurea when control of blood glucose remains or becomes inadequate (HbA1c 59mmol/mol or other higher level agreed with the individual) and insulin is unacceptable or inappropriate. Licensed combinations: Dual therapy with metformin, sulfonylurea or pioglitazone. Triple therapy with metformin & sulfonylurea or pioglitazone. Insulin (with or without metformin) No dose adjustment is necessary based on age. However, dosing of alogliptin should be conservative in patients with advanced age due to the potential for decreased renal function. Continue gliptin therapy only if there is a reduction of 5.5mmol/mol (0.5%) in HbA1c in 6 months. No long term safety data available for these agents. Renal impairment (CrCl, SPC): >50ml/min no dose adjustment 30-50ml/min 50mg daily <30ml/min 25mg daily No dose adjustment is necessary based on age. Limited safety data is available in patients 75 years of age and care should be exercised. Applies to all gliptins: Discuss the potential benefits and risks of treatment with a gliptin with the person to enable them to make an informed decision. Increased risk of pancreatitis associated with all gliptins. Patients should be informed of the characteristic symptoms of acute pancreatitis persistent, severe abdominal pain (sometimes radiating to the back) and encouraged to tell their healthcare provider if they have such symptoms. Link to MHRA warning

13 Type 2 Diabetes - Medications Gliptins (also known as DPP-4 inhibitors) Inhibit dipeptidylpeptidase-4 to increase insulin secretion and to lower glucagon secretion. Drug Notes Formulary choice Linagliptin Licensed combinations: Price per month (Nov14): 5mg daily Dual therapy with metformin Triple therapy with metformin & sulfonylurea Insulin (with or without metformin) Precautions/ Contra-indications/ Patients with complex disease See sitagliptin entry for MHRA warning regarding pancreatitis (applies to all gliptins). No long term safety data available for these agents. Renal impairment (SPC): Does not require dose reduction in renal impairment, No dose adjustment is necessary based on age. However, clinical experience in patients > 80 years of age is limited and caution should be exercised when treating this population.

14 Type 2 Diabetes - Medications Thiazolidinediones (also known as Glitazones) (Pioglitazone is the only available thiazolidinedione) Reduces peripheral insulin resistance, leading to a reduction of blood glucose concentration Drug Notes Formulary choice Precautions/ Contra-indications/ Patients with complex disease Pioglitazone Price per month (Nov14): 15mg -45mg daily NICE guidance (CG87): Consider adding pioglitazone instead of a sulfonylurea as second-line therapy to first-line metformin when control of blood glucose remains or becomes inadequate (HbA1c 48mmol/mol, or other higher level agreed with the individual) if: the person is at significant risk of hypoglycaemia or its consequences (for example, older people and people in certain jobs [for example, those working at heights or with heavy machinery] or people in certain social circumstances [for example, those living alone]), or a person does not tolerate a sulfonylurea or a sulfonylurea is contraindicated. Consider adding a pioglitazone as second-line therapy to first-line sulfonylurea monotherapy when control of blood glucose remains or becomes inadequate (HbA1c 48mmol/mol, or other higher level agreed with the individual) if: the person does not tolerate metformin or metformin is contraindicated. Consider adding pioglitazone as third-line therapy to first-line metformin and a second-line sulfonylurea when control of blood glucose remains or becomes inadequate (HbA1c 59mmol/mol, or other higher level agreed with the individual) and insulin is unacceptable or inappropriate. Consider combining pioglitazone with insulin therapy for a person: who has previously had a marked glucose-lowering response to thiazolidinedione therapy (pioglitazone), or who is on high-dose insulin therapy and whose blood glucose is inadequately controlled. Licensed combinations: Dual therapy with metformin or sulfonylurea. Triple therapy with metformin & sulfonylurea. Insulin (if metformin not appropriate) Pioglitazone is the only thiazolinedione available Continue pioglitazone therapy only if there is a reduction of 5.5mmol/mol (0.5%) in HbA1c in 6 months Do not start or continue pioglitazone in people who: have heart failure (NYHA class I-IV) are at a higher risk of fracture macula oedema a history of bladder cancer or in patients with uninvestigated macroscopic or microscopic haematuria. Risk of bladder cancer: MHRA safety update MHRA guide on patient selection and risk minimisation. Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for the development of cardiac failure. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain, and oedema. Risk of cardiac failure when combined with insulin: MHRA safety update Pioglitazone can cause weight gain. Discuss the potential benefits and risks of treatment with pioglitazone with the person to enable them to make an informed decision. Pioglitazone may be preferable to a gliptin if: the person has marked insulin insensitivity, or a gliptin is contraindicated, or the person has previously had a poor response to, or did not tolerate, a gliptin. Renal impairment (SPC): No dose adjustment is necessary in patients with impaired renal function (creatinine clearance> 4 ml/min). Do not use if hepatically impaired. No dose adjustment is necessary for elderly patients. Start with the lowest available dose and increase gradually, particularly when used in combination with insulin.

15 Type 2 Diabetes - Medications GLP-1 (Glucagon-like peptide-1) Agonists Increase insulin secretion, suppress glucagon secretion, and slow gastric emptying Drug Notes Formulary choice Precautions/ Contra-indications/ Patients with complex disease Lixisenatide Price per month (Nov14): 20 micrograms daily Exenatide (Byetta ) Price per month (Nov14): 5 or 10mcg daily Once daily subcutaneous injection Lixisenatide is currently the GLP-1 agonist with the lowest acquisition cost. Start 10micrograms daily increasing to 20micrograms daily after 2 weeks if tolerated Dual / Triple therapy: As per exenatide (Byetta ) Licensed in combination with: oral glucose-lowering medicinal products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycaemic control. (See exenatide for local patient group comments on use with basal insulin) There is no specific NICE guidance for lixisenatide. Twice daily subcutaneous injection NICE guidance (CG87): Dual / Triple therapy: Can be used in dual or triple therapy regimens when control of blood glucose remains or becomes inadequate (HbA1c 59mmol/mol or agreed individualised target). Patients should be on maximally tolerated doses of oral hypoglycaemic agents and have a BMI; 35.0 kg/m2 in those of European descent (with appropriate adjustment for other ethnic groups) and specific psychological or medical problems associated with high body weight, or < 35.0 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities. Licensed indications: Dual therapy with metformin, a sulfonylurea or pioglitazone. Triple therapy with metformin & a sulfonylurea or metformin & pioglitazone. In combination with insulin: Exenatide (Byetta ) is licensed for addition to patient currently receiving insulin +/- metformin and/or pioglitazone in adults who have not achieved adequate glycaemic control with these agents. The local patient group indicated to receive this combination the person must fulfill the following criteria: BMI >35 and HbA1c > 75mmol/mol and currently using insulin. Prescriber to decide most appropriate GLP-1 agonist after discussion with patient. If all other patient factors are equal prescribe the GLP-1 agonist with the lowest acquisition cost. Prescriber to decide most appropriate GLP-1 agonist after discussion with patient. If all other patient factors are equal prescribe the GLP-1 agonist with the lowest acquisition cost. Dual therapy - continue lixisenatide only if the person has a reduction in HbA1c of 11mmol/mol (1%) after 6 months. Triple therapy - continue lixisenatide only if the person has a reduction in HbA1c of 11mmol/mol (1%) and a 3% loss of initial bodyweight after 6 months. No long term safety data available. Renal impairment (CrCl, SPC): 50-80ml/min no dose adjustment 30-50ml/min use with caution <30ml/min not recommended No dose adjustment required based on age, but limited therapeutic experience in patients > 75yrs. See exenatide for information on hypoglycaemia and pancreatitis risk (applies to all GLP-1 agonists). Dual therapy - continue exenatide only if the person has a reduction in HbA1c of 11mmol/mol (1%) after 6 months. Triple therapy - continue exenatide only if the person has a reduction in HbA1c of 11mmol/mol (1%) and a 3% loss of initial bodyweight after 6 months. No long term safety data available. Renal impairment (CrCl, SPC): 50-80ml/min no dose adjustment 30-50ml/min dose escalation from 5 mcg to 10 mcg should proceed conservatively <30ml/min not recommended Use with caution and dose from 5 mcg to 10 mcg should proceed conservatively in patients >70 years. The clinical experience in patients >75years is very limited. Applies to all GLP-1 agonists: Discuss the potential benefits and risks of treatment with a GLP-1 agonist with the person to enable them to make an informed decision. Routine monitoring of blood glucose levels is only required if the GLP-1 agonist is given in combination with another agent likely to cause hypoglycaemia e.g. sulfonylurea. There have been reports of necrotising and haemorrhagic pancreatitis with GLP-1 agonists, some of which were fatal. If pancreatitis is suspected, treatment with the GLP-1 agonist should be suspended immediately; if pancreatitis is diagnosed, the GLP-1 agonist should be permanently discontinued. (MHRA warning)

16 Type 2 Diabetes - Medications GLP-1 (Glucagon-like peptide-1) Agonists Increase insulin secretion, suppress glucagon secretion, and slow gastric emptying Drug Notes Formulary choice Exenatide prolonged release (Bydureon Price per month (Nov14): 2mg weekly: Once weekly subcutaneous injection Use as per NICE TA248. Exenatide MR is NOT licensed in combination with insulin. NICE TA248 Exenatide prolonged release: Dual therapy: (Met or Glic) + Exenatide MR Prolonged-release exenatide in dual therapy regimens (that is, in combination with metformin or a sulfonylurea) is recommended as a treatment option for people with type 2 diabetes, as described in Liraglutide for the treatment of type 2 diabetes mellitus (NICE technology appraisal 203); that is, only if: the person is intolerant of either metformin or a sulfonylurea, or a treatment with metformin or a sulfonylurea is contraindicated, and the person is intolerant of thiazolidinediones and dipeptidyl peptidase-4 (DPP- 4) inhibitors, or a treatment with thiazolidinediones and DPP-4 inhibitors is contraindicated. Triple therapy: Met + (Glic or Pio) + Exenatide MR Prolonged-release exenatide in triple therapy regimens (that is, in combination with metformin and a sulfonylurea, or metformin and a thiazolidinedione) is recommended as a treatment option for people with type 2 diabetes as described in Type 2 diabetes: the management of type 2 diabetes (NICE clinical guideline 87); that is, when control of blood glucose remains or becomes inadequate (HbA1c 59 mmol/mol or agreed individualised target), and the person has: a body mass index (BMI) 35 kg/m2 in those of European family origin (with appropriate adjustment for other ethnic groups) and specific psychological or medical problems associated with high body weight or a BMI < 35 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities. Licensed combinations: Dual therapy with metformin, a sulfonylurea or pioglitazone. Triple therapy with metformin & sulfonylurea or metformin & pioglitazone. Prescriber to decide most appropriate GLP-1 agonist after discussion with patient. If all other patient factors are equal prescribe the GLP-1 agonist with the lowest acquisition cost Precautions/ Contra-indications/ Patients with complex disease Dual therapy - continue exenatide MR only if the person has a reduction in HbA1c of 11mmol/mol (1%) after 6 months. Triple therapy - continue exenatide MR only if the person has a reduction in HbA1c of 11mmol/mol (1%) and a 3% loss of initial bodyweight after 6 months. No long term safety data available. Renal impairment (CrCl, SPC): 50-80ml/min no dose adjustment <50ml/min not recommended No dose adjustment required based on age, but limited therapeutic experience in patients > 75yrs. See exenatide for information on hypoglycaemia risk and warning about pancreatitis risk (applies to all GLP-1 agonists).

17 Type 2 Diabetes - Medications GLP-1 (Glucagon-like peptide-1) Agonists Increase insulin secretion, suppress glucagon secretion, and slow gastric emptying Drug Notes Formulary choice Liraglutide Price per month (Nov14): 1.2mg daily Once daily subcutaneous injection Use as per NICE TA mg daily for 2 weeks, increasing to 1.2mg daily if tolerated. Liraglutide 1.8 mg daily is not recommended for the treatment of people with type 2 diabetes. (NICE TA203) NICE TA203 Liraglutide Dual therapy: (Met or Glic) + Liraglutide Liraglutide 1.2 mg daily in dual therapy regimens (in combination with metformin or a sulfonylurea) is recommended as an option for the treatment of people with type 2 diabetes, only if: the person is intolerant of either metformin or a sulfonylurea, or treatment with metformin or a sulfonylurea is contraindicated, and the person is intolerant of thiazolidinediones and dipeptidyl peptidase-4 (DPP- 4) inhibitors, or treatment with thiazolidinediones and DPP-4 inhibitors is contraindicated. Triple therapy: Met + (Glic or Pio) + Liraglutide Liraglutide 1.2 mg daily in triple therapy regimens (in combination with metformin + sulfonylurea, or metformin + thiazolidinedione) is recommended as an option for the treatment of people with type 2 diabetes, only if used as described for exenatide in NICE CG87; that is, when control of blood glucose remains or becomes inadequate (HbA1c 59mmol/mol, or agreed individualised target), and the person has BMI: 35 kg/m2 in those of European descent (with appropriate adjustment for other ethnic groups) and specific psychological or medical problems associated with high body weight, or < 35 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities. Licensed in combination with: oral glucose-lowering medicinal products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycaemic control. Prescriber to decide most appropriate GLP-1 agonist after discussion with patient. If all other patient factors are equal prescribe the GLP-1 agonist with the lowest acquisition cost Precautions/ Contra-indications/ Patients with complex disease Dual therapy - continue liraglutide only if the person has a reduction in HbA1c of 11mmol/mol2 (1%) after 6 months. Triple therapy - continue liraglutide only if the person has a reduction in HbA1c of 11mmol/mol2 (1%) and a 3% loss of initial bodyweight after 6 months. No long term safety data available. Renal impairment (CrCl, SPC): 30-90ml/min - no dose adjustment <30ml/min not recommended No dose adjustment required based on age, but limited therapeutic experience in patients > 75yrs. See exenatide for information on hypoglycaemia risk and warning about pancreatitis risk (applies to all GLP-1 agonists).

18 Type 2 Diabetes - Medications GLP-1 (Glucagon-like peptide-1) Agonists Increase insulin secretion, suppress glucagon secretion, and slow gastric emptying Drug Notes Formulary choice Dulaglutide Price per month (June 15): 0.75mg or 1.5mg weekly Once weekly subcutaneous injection NICE advice [ESNM59] June 2015 Dulaglutide is licensed for improving glycaemic control in adults with type 2 diabetes mellitus as: Monotherapy: 0.75mg weekly, when diet and exercise alone do not provide adequate glycaemic control in people for whom the use of metformin is considered inappropriate due to intolerance or contraindications. Add on therapy: 1.5mg weekly, in combination with other glucose lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control. The SPC and PIL are not specific in lisiting exactly which combinations are included in the product licence, the combinations that were used to support this indication in clinical trials were: Dulaglutide plus metformin Dulaglutide plus metformin and sulphonylurea Dulaglutide plus metfomrin and pioglitazone Dulaglutide plus metformin and prandial insulin (N.B. not with basal insulin) Dulaglutide and prandial insulin (N.B. not with basal insulin) May be used in mild to moderate renal impairment. May be of benefit for patients with compliance problems, such as dexterity with other devices or dosing regimens Precautions/ Contra-indications/ Patients with complex disease Elderly patients > 75 years recommended starting dose 0.75 mg weekly Renal impairment - No dosage reduction in mild to moderate. There is limited experience in severe renal failure or end stage renal disease so its use is not recommended. Hepatic impairment No dosage adjustment required See exenatide for information on hypoglycaemia risk and warning about pancreatitis risk (applies to all GLP-1 agonists).

19 Type 2 Diabetes - Medications Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitor Reversibly inhibits sodium-glucose co-transporter-2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion. Drug Notes Formulary choice Dapagliflozin Price per 28 days (Nov 14): 5 or 10mg daily NICE TA288: Dual therapy: Met + Dapagliflozin (as per gliptins): Dapagliflozin in a dual therapy regimen in combination with metformin is recommended as an option for treating type 2 diabetes, only if it is used as described for gliptins in Type 2 diabetes: the management of type 2 diabetes (NICE clinical guideline 87). Dapagliflozin + insulin: Dapagliflozin in combination with insulin with or without other antidiabetic drugs is recommended as an option for treating type 2 diabetes. The NICE TA states that dapagliflozin is not recommended for triple therapy. However, this is considered acceptable practise locally if dapagliflozin is used in combination with metformin and gliclazide. Licensed in combination with: other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control. Prescriber to decide most appropriate SGLT2 inhibitor after discussion with patient. If all other patient factors are equal prescribe the SGLT2 inhibitor with the lowest acquisition cost. Precautions/ Contra-indications/ Patients with complex disease No long term safety data available. Licensed for initiation in adults between 18 and 75 years only. Renal impairment (egfr or CrCl SPC): >60ml/min no dose adjustment <60ml/min not recommended Due to its mechanism of action, patients taking dapagliflozin are at increased risk of urinary tract infection and will test positive for glucose in their urine. Increases diuresis associated with a modest decrease in blood pressure (more pronounced in patients with very high blood glucose concentrations). Not recommended for patients receiving loop diuretics or who are volume depleted e.g. due to acute illness (such as gastrointestinal illness). While a causal relationship between dapagliflozin and bladder cancer is unlikely, as a precautionary measure, dapagliflozin is not recommended for use in patients concomitantly treated with pioglitazone. When treating patients who are taking an SGLT2 inhibitor (canagliflozin, dapagliflozin or empagliflozin): Test for raised ketones in patients with symptoms of diabetic ketoacidosis (DKA); omitting this test could delay diagnosis of DKA if you suspect DKA, stop SGLT2 inhibitor treatment if DKA is confirmed, take appropriate measures to correct the DKA and to monitor glucose levels inform patients of the symptoms and signs of DKA (see below); advise them to get immediate medical help if these occur be aware that SGLT2 inhibitors are not approved for treatment of type 1 diabetes please continue to report suspected side effects to SGLT2 inhibitors or any other medicines on a Yellow Card Signs and symptoms Thirst Feeling tired and lethargic Blurry vision Abdominal pain, nausea, vomiting Breathing changes (deep sighing breaths) Ketones present Collapse/unconsciousness.

20 Type 2 Diabetes - Medications Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitor Reversibly inhibits sodium-glucose co-transporter-2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion. Drug Notes Formulary choice Canagliflozin Price per 28 days (Nov 14): 100mg or 300 mg daily or For use as per NICE TA315 Note that although canagliflozin is licensed for monotherapy, the APC have only approved it for use as per NICE TA315. NICE TA315: Dual therapy: Met + Canagliflozin Canagliflozin in a dual therapy regimen in combination with metformin is recommended as an option for treating type 2 diabetes, only if: a sulfonylurea is contraindicated or not tolerated or the person is at significant risk of hypoglycaemia or its consequences. Triple therapy: Met + (Glic or Pio) + Canagliflozin Canagliflozin in a triple therapy regimen is recommended as an option for treating type 2 diabetes in combination with: metformin and a sulfonylurea or metformin and a thiazolidinedione. Canagliflozin + insulin: Canagliflozin in combination with insulin with or without other antidiabetic drugs is recommended as an option for treating type 2 diabetes. Licensed in combination with: other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control. Prescriber to decide most appropriate SGLT2 inhibitor after discussion with patient. If all other patient factors are equal prescribe the SGLT2 inhibitor with the lowest acquisition cost. Precautions/ Contra-indications/ Patients with complex disease No long term safety data available. Licensed for adults aged over 18 years only. For patients over 65 years renal function and risk of volume depletion should be taken into account. Renal impairment (egfr or CrCl, SPC): 60-89ml/min no dose adjustment. <60ml/min do not initiate canagliflozin. Max dose 100mg daily if egfr or CrCl persistently falls below 60ml/min whilst on canagliflozin. <45 ml/min- discontinue canagliflozin if egfr or CrCl persistently falls below 45ml/min whilst on canagliflozin. Due to its mechanism of action, patients taking canagliflozin are at increased risk of urinary tract infection and will test positive for glucose in their urine. When treating patients who are taking an SGLT2 inhibitor (canagliflozin, dapagliflozin or empagliflozin): test for raised ketones in patients with symptoms of diabetic ketoacidosis (DKA); omitting this test could delay diagnosis of DKA if you suspect DKA, stop SGLT2 inhibitor treatment if DKA is confirmed, take appropriate measures to correct the DKA and to monitor glucose levels inform patients of the symptoms and signs of DKA (see below); advise them to get immediate medical help if these occur be aware that SGLT2 inhibitors are not approved for treatment of type 1 diabetes please continue to report suspected side effects to SGLT2 inhibitors or any other medicines on a Yellow Card