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Microsoft word - final management of hba1c pathway 19.4.13.docBlood Glucose Control Management Pathway for People with Type 2 Diabetes After diagnosis discuss lifestyle changes, refer to DESMOND and provide a newly diagnosed information pack.
At ALL appointments reinforce lifestyle messages, check on medication adherence and develop a collaborative care plan with the person who has diabetes.
First and second line therapy
If BMI < 22 or a patient is acutely symptomatic at presentation seek advice from diabetes team as early insulin initiation may be required. See early/urgent insulin initiation guideline Start therapy after 3 months of lifestyle changes if HbA1c remains > 48mmol/mol. Usual target HbA1c 48-58mmol/mol. Some patients require a different individualised HbA1c target level NOTE: NICE cautions against the use of highly intensive management strategies to achieve levels of <48mmol/mol. FIRST LINE THERAPY - Metformin
Other options for 2nd line therapy:
Start at a dose of 500mg daily. Increase to 500mg twice daily after 2 weeks and increase by 500mg every 2 weeks to a reach a dose of 1g twice daily 1. Consider a gliptin or pioglitazone in Doses should be taken with meals to minimise GI side effects. If GI intolerance occurs, try metformin modified release or reduce dose to previously tolerated dose. Before starting metformin check eGFR and remember renal precautions (see box overleaf for details). Check HbA1c after patient has been on maximum tolerated dose for 3 months
tolerated. 2. Consider a gliptin or pioglitazone in If Hba1c > target level add in 2nd line therapy
combination with SU if metformin is
contraindicated or not tolerated.
Locally sitagliptin is 1st line gliptin of
Sulfonylurea (SU) – e.g. gliclazide
For gliclazide, start at a dose of 40-80mg daily with meals (higher doses divided). Titrate dose every 2 weeks according to pre-meal blood glucose levels. Target pre-meal blood glucose level is 4- 6mmol/l. If the patient is not self testing, titrate dose according to HbA1c level every 3 months. It is recommended that patients Check HbA1c after 3 months and ONLY
taking SU’s self monitor their blood glucose in line with the Lambeth/Southwark Self-Monitoring Blood Glucose Guidance (September 2012) continue a gliptin or pioglitazone if
A SU should be used as first line therapy if rapid response required due to symptomatic hyperglycaemia, if a person is not overweight (BMI < 25) or where
there is a reduction in HbA1c of ≥
6mmol/mol (0.5%) and target HbA1c is
Check HbA1c after patient has been on maximum tolerated dose for 3 months
If Hba1c > target level add in 3rd line therapy
Third line therapy if HbA1c is between 58 – 75mmol/mol
Third line therapy if HbA1c is more than
Refer to local community diabetes team* for insulin initiation through a structured programme. Options if insulin is unacceptable or other criteria are met:
Oral agents in triple therapy
GLP1 receptor agonists (injectable agents)
Refer to local community diabetes team for insulin 1. Consider if BMI ≥ 35 or if BMI ≤ 35 where insulin is unacceptable for initiation through a structured programme. The local 1. Consider adding gliptin or pioglitazone if insulin is occupational reasons or weight loss would benefit other co-morbidities community diabetes team will advise on continuation 2. Refer to community diabetes team for initiation. LY continue a gliptin or pioglitazone therapy if there is a
3. ONLY continue GLP1 treatment if there is an HbA1c reduction of at reduction of ≥6mmol/mol (0.5%) in HbA1c at 6 months and target least 11mmol/mol (1%) and a weight loss of at least 3% of initial body 3. If target HbA1c is not achieved refer to community diabetes 4. If a GLP-1 is continued, check HbA1c every 6 months and only continue if weight loss and target HbA1c are maintained.
Check HbA1c 3 months after any therapy change. Move to next step of therapy if target is not achieved. Discuss/refer to diabetes team if clinical concern at any stage
ADDITIONAL INFORMATION –
this information is not exhaustive. Please refer to product literature for full list of doses, cautions and contra-indication and drug interactions – available via www.medicines.org.uk Metformin (biguanide):
Sulfonylureas - NB gliclazide is the local SU of choice
Metformin reduces cardiovascular events in overweight and obese patients to a greater extent than Patients should be educated about the risks of hypoglycaemia with sulfonylureas, particularly if renally impaired. predicted by its glucose lowering effects Refer to local self monitoring of blood glucose guideline and DVLA guidance for drivers with diabetes using Modified release (M/R)
500mg once daily, increased every 10-15 days, max. 2g once daily with evening meal. If control not Weight gain averaging 2-4kg is a recognised consequence of sulfonylurea therapy. Always reassess the patient and emphasise lifestyle issues before prescribing Patients taking less than 2g daily of standard release can start on same daily dose of M/R Sulfonylureas and the kidney
Metformin and the kidney
SU’s should be used with care in those with mild to moderate renal impairment due to the increased risk of Do not start metformin if eGFR <45ml/min. Use under specialist advice only. hypoglycaemia. Avoid where possible in severe renal impairment.
Review metformin dose if Cr>130µmol/l or eGFR <45ml/min Sulfonylureas and the liver
Stop/avoid metformin if Cr>150µmol/l or eGFR <30ml/min Avoid or reduce dose in severe hepatic impairment due to an increased risk of hypoglycaemia Pioglitazone
Gliptins and GLP-1 agonists
Start at 15-30mg once daily, increased to 45mg once daily according to response. Start with lowest Gliptins
possible dose in the elderly and increase gradually. Where applicable, dose of concurrent sulfonylurea or Locally sitagliptin is 1st line gliptin of choice. Linagliptin is reserved for use in patients with severe renal
Pioglitazone is contraindicated in people with a history of heart failure, uninvestigated macroscopic For sitagliptin the dosing is 100mg once daily, reduced to 50mg once daily if eGFR is between 30-50ml/min haematuria and previous or active bladder cancer or 25mg once daily if eGFR <30ml/min. Caution is advised when considering use in cardiovascular disease or in combination with insulin, or in Linagliptin should ONLY be considered as a treatment option in patients with severe renal impairment
those with an increased risk of bone fractures or risk factors for bladder cancer. Consider pioglitazone in preference to a gliptin if there is a contraindication or poor response to the gliptin The MHRA has warned that an increased risk of acute pancreatitis has been identified for all approved
gliptins. Patients should be informed of the characteristic symptoms of acute pancreatitis and encouraged to report these to their healthcare provider. If pancreatitis is suspected, the gliptin and other potentially suspect Monitor liver function before treatment and periodically thereafter. Advise patients to seek immediate medical attention if symptoms such as nausea, vomiting, abdominal pain, fatigue and dark urine develop. Consider a gliptin in preference to pioglitazone if there is a contraindication, previous poor response or pioglitazone is not tolerated or if further weight gain would cause significant problems The European Medicines Agency has advised that pioglitazone remains a valid treatment option for certain GLP-1 agonist (exenatide and liraglutide)
patients with type 2 diabetes. Individual’s risks-benefits should be taken into account when initiating Refer patients to the local community diabetes team for initiation of these agents. Patients who use these pioglitazone in conjunction with the latest EMA safety recommendations. The safety and efficacy of agents in combination with insulin will have therapy managed and prescribed by the local community pioglitazone should be reviewed after 3-6 months and it should be stopped in patients not responding adequately. Pioglitazone’s efficacy and safety should be reviewed (e.g. 3-6 monthly) in patients continuing therapy. See MHRA advice (August 2011) for further details and the summary of product characteristics The use of the once weekly exenatide formulation will ONLY be managed and prescribed by the specialist
The GLP-1 receptor agonist liraglutide can also be initiated as a 2nd line option, where all other options are unsuitable, in line with the NICE criteria outlined for its 3rd line use GLP-1 agonists have been associated with a risk of pancreatitis. Patients should be informed of the characteristic symptoms of acute pancreatitis and encouraged to report these to their healthcare provider. If pancreatitis is suspected, the GLP-1 agonist and other potentially suspect medicines should be discontinued. The MHRA has warned about the risks of severe pancreatitis and renal failure associated with References
Additional information – HbA1c
NICE clinical guideline 87 – type 2 diabetes, available
Standard release exenatide is not recommended for use in patients with end-stage renal disease or severe via http://guidance.nice.org.uk/CG87 . Last accessed
renal impairment (creatinine clearance (CrCl) <30 mL/min) and used with caution when CrCl between 30- 15.03.13
MHRA Drug Safety Update September 2012, vol 6, issue
50ml/min. Liraglutide should be avoided when eGFR <60ml/min and exenatide m/r to be avoided when CrCl MHRA Drug Safety Update Volume 2 Issue 8, March
BNF 64 September 2012
SPCs for exenatide and liraglutide, available via
www.medicines.org.uk (accessed 15.03.13)
Expert opinions of local diabetes clinicians and
At time of writing, dapagliflozin is not currently on the local formulary and its place in therapy is
yet to be agreed. Prescribers are advised to await further guidance before prescribing this agent.
University Hospitals of Leicester- glycaemic
management oral agents May 2012
NHS Rotheram Type 2 diabetes patient objective
guidelines. Review date May 2013.
*Insulin initiation: It is recognised that a small number of practices are qualified to initiate insulin. Where this is the case, referral to the community team for initiation is not
always required. If in doubt, check with the community teams.
If you have any queries or comments on this guideline please contact the Medicines teams: Southwark CCG 0207 525 3253 or Lambeth CCG: 0203 049 4197
Produced: April 2013. Review Date: December 2014
LISTE DES PUBLICATIONS Articles publiés dans des revues avec comité de lecture : 1) Rahmouni, A. , Malinge, J-M, Schwartz, A. and Leng, M. Comparison Between poly(dG-dC).poly(dG-dC) and DNA Modified by cis-diamminedichloroplatinium (II): Immunological and Spectroscopic Studies. J. Biomol. Structure and Dynamics (1985) 3 , 363-375. 2) Rahmouni, A. and Leng, M. Reaction of Nu