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Drugs in diabetes

Drugs in diabetes
24 September 2012

While there is general acknowledgement of the broader challenges associated with delivering optimal diabetes care, medicines management is crucial for three reasons:

While there is general acknowledgement of the broader challenges associated with delivering optimal diabetes care, medicines management is crucial for three reasons:

1.    Medicines use and procurement is one of the 12 QIPP priority areas and one of the few areas which is within direct control of the GP prescriber, therefore presenting opportunities to achieve rapid impact in terms of outcomes and spend.
2.    Medication is one of the NICE quality standards for diabetes in adults.
3.    The new GP led commissioners have a unique opportunity to shift the emphasis of medicines management away from purely cost savings, to quality and outcomes balanced against expenditure. Keeping patients well, out of hospital and extending their quality and length of life.

Diabetes is a disease which has a significant financial burden on the NHS and the economy due to the care associated with related complications.

The current UK prevalence is estimated to be 2.9m1 for the known diagnosed adult population, 85% of which is attributed to England.

However the London School of Economics Diabetes Report 20122  estimates a UK prevalence closer to 3.6m (not including Northern Ireland), which includes paediatric prevalence too. The prevalence will continue to rise due to the growing national problems with obesity. Early identification and diagnosis of the disease is still a challenge with 500,000 estimated to have the disease but are currently undiagnosed.3 The National Diabetes Audit published in Dec 2011 revealed that 70,000 people a year are dying from diabetes, with up to 24,000 of those people suffering an avoidable death.4

For the UK economy, it is currently estimated that 10% of the NHS budget is spent on Diabetes care3 which if we use the NHS budget for 2011/12 of approx £106 billion,5 this equates to £10.6 billion per year. For the UK as a whole, total diabetes drug spend reached an estimated £3.1 billion in 2010.2

Poor diabetes control and complications also have an indirect cost implication on the UK economy, in terms of absenteeism, early retirement and social benefit payments. The 2010 estimate was £15.4bn in the UK based on a diabetic population of approx 1,728,290 of patients in active employment on an average daily earning of £117.00.2

The major cause of death and complication in patients with type 2 diabetes is Cardiovascular (CV) disease with more that 60% of all patients with type 2 diabetes dying of CV disease, and an even greater percentage suffering serious complications.6  Furthermore hypertension and raised blood lipid levels are known to be risk factors for coronary heart disease, particularly in patients with type 2 diabetes.6-8

Some studies have shown that intensive blood glucose–lowering strategies (targeting a HbA1c < 6.0%) reduce the risk of cardiovascular disease and death but often require a prolonged period of follow-up before benefits become evident.9 However the ACCORD study suggests that less-intensive glycaemic targets may be indicated in patients with type 2 diabetes considered at high risk of heart disease, and that there is a need for aggressive lipid and blood pressure management in subjects with type 2 diabetes.10

If drug expenditure in diabetes is only a fraction of the total costs of treating a patient with diabetes, what is the role of medicines management? The biggest cost associated with diabetes care is attributed to In- patient episodes. In-patient costs constitute an estimated 67% of the total indirect costs per patient in the UK.2

While the direct cost of hypoglycaemic drugs is relatively small, the consequences of not prescribing optimally, monitoring medication compliance and not monitoring outcomes of treatment are great in terms of the in-patient costs and to a lesser degree out-patient costs associated with diabetes related complications.

Therefore the value to be gained from a local medicines management strategy is in supporting the GP practice in keeping patients out of hospital through the optimal use of, and adherence to hypoglycaemic agents such as Metformin; Sulphonylureas; Insulin; and Secondary Prevention with CV Disease protecting agents such as Losartan, Ezetimbe and Simvastatin. In addition, the monitoring of the effectiveness of these drugs in controlling the disease for a patient.

Recent research shows that 3−4% of UK hospital admissions are a result of avoidable medicine-related illness.11 Between 11% and 30% of these admissions result from patients not using their medicines as recommended by the prescriber.12  In general 50% of medicines are not taken as prescribed, and non-compliance is a cause of ill-health, premature death and significant avoidable cost to the NHS. Polypharmacy increases the risk of adverse reactions and hospital readmissions.13 NHS expenditure on hospital admissions, excluding critical care costs, was approximately £16.4 billion in 2006–07.13 Therefore, the costs of admissions resulting from patients not taking medicines as recommended is estimated to be between £36 million and £196 million in 2006–07.13 These admissions and associated costs would be expected to decrease as medicines adherence increases.12

Direct spend per patient per year for both Type 1 and Type 2 equates to an estimated2:
Total drugs (diabetic and non-diabetic drugs) –    £798.00
In-patient costs (due to complications) –    £2,552.00
Out-patient costs (without drugs) –    £367.00
GRAND TOTAL    £3,717.00 per patient per year5

Reducing the scale of the downstream costs should be a key focus for diabetes care services, thus creating a strong case for medicines management to support blood glucose control; blood pressure and lipid regulation. The local medicines management strategy should strongly consider the incorporation of the following:

1.    Level 2 Medication reviews– treatment review with patient’s full notes.
2.    Level 3 Medication reviews – Clinical medication review, a face to face review of medication and condition. (Reserve for high costs patients and poorly controlled patients.)
3.    Optimisation of Metformin prescribing where
clinically appropriate (titrating to maximum dosage
of 1500mg per day).
4.    Medication adherence monitoring and coaching face to face with patients.
5.    Implementation of cost savings associated with the prescribing of branded ACE Inhibitors; Statins; and Angiotensin II Reception Antagonists (ARBs).
6.    Risk profiling to identify high risk patients (those consuming the greatest resources) and intervention cost –benefit analysis.

The objective of drug treatment in type 2 diabetes is to delay or prevent the onset of microvascular and macrovasular complications by managing blood glucose levels, blood pressure and lipid levels in patients. Current practice aims to achieve glycated haemoglobin (HbA1c) level of 7%, or 7.5% for those at risk of severe hypoglycaemia; however it is a well-known fact by healthcare professionals that these targets are not achieved by everyone.14

Although lifestyle interventions (diet and physical activity) are the first-line treatments for the management of type 2 diabetes, most people will require the addition of oral glucose-lowering drugs. Type 2 diabetes is progressive, with secretion of insulin decreasing over time, resulting in most people ultimately needing insulin.

The preferred hypoglycaemic agents recommended by NICE guidelines are shown in table 1.14

Newer hypoglycaemic drugs and insulins

Although the newer hypoglycaemic drugs are effective at reducing HbA1c levels, there is a lack of safety data associated with their long term use. The potential benefits of these drugs should be weighed against the risks associated with adding another agent to a drug regimen.


•    There is no definite evidence to support positive patient oriented outcomes.
•    There have been cardiovascular safety concerns with Glitazones,15 for example combination with insulin can cause heart failure, and other safety concerns such as fractures, possibly associated with bladder cancer.
•    Rosiglitazone was withdrawn in 2010 due to ischaemic heart disease.
•    Eye disorders such as new-onset or worsening diabetic macular oedema with decreased visual acuity has been reported with rosiglitazone and pioglitazone. Many of these patients reported concurrent peripheral oedema. Whether there is a direct association between rosiglitazone or pioglitazone and macular oedema is unclear.
•    There is a possibility of weight gain with glitazones.16
•    Glitazones are costly.

2. Insulins

A UK study17 found insulin analogues cost the NHS millions. NICE recommends human NPH insulin in type 2 diabetes patients. Newer long-acting insulins detemir, glargine etc. are recommended in specific circumstances by NICE.18 The newer long –acting insulins do not offer significant advantages over the human NPH insulin and are a lot more expensive.19

Blood Glucose Monitoring
Blood glucose home testing has its pros and cons.

Diabetes Management Challenges
The following case study (see print edition) provides a worked example of a diabetes management challenge faced by prescribers.


Dose titration of metformin, as detailed below,20 could help in this scenario.

1.    Start with low-dose metformin (500 mg) taken once or twice daily with meals (breakfast and/or dinner) or 850 mg once daily.
2.    After 5–7 days, if gastrointestinal side effects have not occurred, increase dose to 850mg, or two 500 mg tablets, twice daily before breakfast and/or dinner.
3.    If gastrointestinal side effects appear as dose increases, decrease to previous lower dose and try to increase the dose at a later stage.
4.    The maximum effective dose can be up to 1,000 mg twice daily but is often 850 mg twice daily. Modestly greater effectiveness has been observed with doses up to about 2,500 mg/day. Gastrointestinal side effects may limit the dose that can be used.
5.    Based on cost considerations, generic metformin is the first choice of therapy.

A longer-acting formulation is available and can be tried giving once daily if gastrointestinal side effects persist.


Good control of blood pressure and blood glucose levels has now been achieved. The last HbA1c was 7.5 mmol/l, and the patient is adhering to her treatment regime very well.

Discussion Points

•    Metformin tablets should be considered as first line treatment for all patients even if they are not over weight.18 Dosage titration should be used.
•    Sulphonylureas should be considered as first line treatment in patients who can’t tolerate metformin. There is risk of hypoglycaemia with sulphonylureas hence the patient should be advised of this side effect.18
•    A ‘New Medicines Review’ (NMR) would have picked up the Metformin adherence issue.
•    Lifestyle changes should be supported by SMART goal setting


Challenges in designing and implementing a medicines management strategy for diabetes are centred around the time and financial investment required to achieve patient concordance and adherence.

Also, to plough through practice level and secondary care level data to evaluate the cost benefit of patient interventions. Where the balance is wrong, identifying the relevant changes to make, and support to provide, to address the imbalance. Leveraging a shared, skilled pharmacy resource across the clinical commissioning group will provide the capability to help achieve the required in-patient related savings associated with diabetes care.

Yinka Makinde, Pharmacist and Director of Health Capital Partners Ltd, and Mitta Bathia, Pharmacist and Director of CP Updates

1. Diabetes UK. Reports and statistics. October 2011. Available at:
2. Kanavos P, Van den Aardweg S, Schurer W. Diabetes expenditure, burden of disease and management in 5 EU countries. London: London School of Economics; January 2012.
3. Diabetes UK. Diabetes in the UK 2010: Key statistics on diabetes. March 2010. Available at:
4. NHS Information Centre. 2010-11 National Diabetes Audit. Available at:
 5. Department of Health. Spending Review 2010. Available at:
6. NICE Guidelines. Management of Type 2 Diabetes; Management of blood pressure and blood lipids. London: NICE; 2002.
7. The National Collaborating Centre for Chronic Conditions. Type 2 Diabetes: National Clinical Guidelines for Management in Primary and Secondary Care (Update). 2008
8. [No authors listed]. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53.
9.  Nathan DM, Cleary PA, Backlund JY, et al. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group: Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353:2643-53.
10. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of Intensive Glucose Lowering in Type 2 Diabetes. N Engl J Med 2008;358:2545-59.
Available at:
11. Meyer J. Concordance: and opportunity for partnership in medicine-taking. Nursing Times Research 2001;6:564-5.
12. NICE. Costing Statement – Medicines adherence: Involving patients in decisions about prescribed medicines & supporting adherence. January 2009. Available at:
13. The National Collaborative Medicines Management Services Programme. Room for review – A guide to medication review: the agenda for patients, practitioners & managers. 2002.
14. NICE Guidelines. NICE short clinical guideline 87 – Type 2 diabetes: newer agents. Available at:
15. MHRA 2007 & 2011. Glitazones for diabetes – Safety Information.
16. NICE. Full clinical guidance 66: Diabetes type 2. May 2008. Available at:
17. Holden SE, et al. Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin. BMJ Open 2011; 2e000258. Available at:
18. NICE CG66 Full guideline May 2008 accessed on 27.04.2012 at: live/11983/40803/40803.pdf
19. Improving outcomes in type 2 diabetes. MeRec Bulletin June 2011:21;5.
20. Nathan DM, Buse JB, Davidson MB et al. Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy.  Diabetes Care 2008;31(12).

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