Nearly Nine Out Of Ten Patients With Type 2 Diabetes Achieve QoF HbA1c Targets With Repaglinide And Metformin

Main Category: Diabetes
Article Date: 31 Aug 2008 - 0:00 PDT

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Nearly nine out of ten patients with type 2 diabetes achieved the Quality Outcomes Framework (QoF) HbA1c target of <7.5% with a repaglinide [PRANDIN®] and metformin treatment strategy says a new study review published in Clinical Therapeutics1.

Furthermore, updated National Institute for Clinical Excellence (NICE) guidance on the management of type 2 diabetes is recommending for the first time that rapid-acting insulin secretagogues (such as repaglinide) may be considered as a first option to add to metformin in patients with non routine daily patterns to assist in attaining glucose control to their individual target.

Repaglinide has a distinct mode of action that helps control HbA1c by predominantly targeting post prandial glucose7. The new NICE guidance highlights the importance of detecting and treating raised prandial glucose8 (> 8.5 mmol/litre) when HbA1c levels remain above target despite well controlled pre-meal glucose levels (< 7.0 mmol/litre). This new recommendation is supported by studies which have shown that PPG becomes the most important contributor to HbA1c levels below a HbA1c of 8.4%3.

An analysis of the repaglinide and metformin treatment from 2005/6 found that only six out of ten patients were achieving the HbA1c target3. The new review in Clinical Therapeutics concludes that the combination offers a good early treatment option. Furthermore, the synergy shown in this study has not been seen with newer agents, such as sitagliptin, when combined with metformin5. Achieving stringent HbA1c targets is crucial to long-term management of type 2 diabetes and to reducing the risk of complications such as nerve damage, eye, kidney and heart disease.

As both drugs are taken orally at or before mealtimes, it presents an easy step for patients to add repaglinide to existing metformin therapy for improved glycaemic control.

This is particularly relevant to people with non-routine lifestyles - those unable or unlikely to eat regularly - as the combination can be taken at or before mealtimes, regardless of when they fall.

Non-routine lifestyles describes anyone who eats irregularly whether it is due, for example, to busy work patterns or shift work or to fasting for religious or cultural reasons.

Repaglinide works to lower HbA1c through its primary action on postprandial glucose, in patients with an HbA1c <8.4%4. Metformin meanwhile deals most effectively with the basal or fasting glucose level. Professor Anthony Barnett, Professor of Medicine and Clinical Director Diabetes and Endocrinology, Heart of England NHS Foundation Trust, commented: "This new analysis presents a win:win scenario for both GPs and their patients. Firstly for GPs, prescribing repaglinide and metformin together, as an early option, rather than monotherapy, helps nine out of ten patients achieve the stringent HbA1c QoF target of ≤7.5%. This is very welcome as only 6 out of ten achieved such targets in 2005/6.

"Secondly, for patients, both products are easy to take together at mealtimes. Whilst this is most relevant to those with irregular mealtimes, it has implications for all people who may regularly, or perhaps even only occasionally, skip meals or have to change the timings of their meals to fit in with their lifestyles." At study entry patients were on metformin at an average daily dose of 1.8g but no patients had optimal glycaemic control (HbA1c < 7.1%) yet by the end of the study 59% of patients in the combined group (repaglinide added to metformin) were optimally controlled with HbA1c reduced overall by 1.41% (p=0.0016) from a baseline of 8.3%.

The review, a re-analysis by Moses1, highlights that 89% of patients receiving metformin and repaglinide achieved the QoF HbA1c target of ≤7.5%, compared with 43% and 42% of patients on metformin and repaglinide monotherapy respectively. These results also compare favourably with other combinations of oral antidiabetic treatments such as sitagliptin plus metformin HCL. In two different studies that included similar patient populations 47% of patients receiving sitagliptin plus metformin achieved the EASD HbA1c target of <7% at 24 weeks4 (baseline 8%) while 56% patients treated with metformin plus repaglinide achieved HbA1c of <7% in just 12 weeks (baseline 8.3%)1. The CONTROL DM study conducted with repaglinide plus metformin has previously shown up to 70% of patients can achieve this target from a starting HbA1c of 8.4%. (Reboussin 2004)

The original study, on which the reanalysis was centred, had three arms and was a randomised, double blind, parallel-group performed at nine centres in Australia. Patients were randomised to either continue with their pre-study dose of metformin (n=27); to continue with their pre-study dose of metformin with the addition of repaglinide (n=27), or to receive repaglinide alone (n=29)3. For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period.

Type 2 diabetes develops when the body can still make some insulin, but not enough, or when the insulin that is produced does not work properly (known as insulin resistance). In most cases this is linked with being overweight. This type of diabetes usually appears in people over the age of 40, though in South Asian and African-Caribbean people often appears after the age of 25. However, recently, more children are being diagnosed with the condition, some as young as seven. Type 2 diabetes is the more common of the two main types and accounts for between 85 - 95% of all people with diabetes.

There are currently over 2.3 million people with diabetes in the UK and more than half a million people with diabetes who have the condition and don't know it.

About HbA1c

HbA1C is a measure of the average blood glucose level over the previous 8-12 weeks and is comprised of Fasting Plasma Glucose (FPG) and Post Prandial Glucose (PPG). Close monitoring of HbA1C levels is essential for optimal glycaemic control. Because HbA1c is a measure of average fasting plasma glucose and postprandial plasma glucose levels over the preceding 120 days, treatment regimens that target both fasting and postmeal plasma glucose are needed to achieve optimal glycaemic control.

At least once a year, long term diabetes control is checked by taking a blood sample. The most common test is the HbA1c test, which indicates blood glucose levels for the previous 2-3 months. Individuals at risk of severe hypoglycaemia should aim for an HbA1c of less than 7.5 per cent. However, any reduction in HbA1c levels (and therefore, any improvement in control), is still considered to have beneficial effects on the onset and progression of complications.

Post Prandial (mealtime) Glucose (PPG)

The development of type 2 diabetes is characterised by a progressive decline in insulin action and deterioration of β-cell function. Prior to clinical diabetes, these metabolic abnormalities are first evident as elevations in postmeal plasma glucose. Epidemiological studies have shown a strong association between postmeal and postchallenge glycaemia and cardiovascular risk and outcomes. Monnier and colleagues have also showed that in people with HbA1c levels 8.4-7.3%, the contribution of postmeal plasma glucose to overall HbA1c was ≈50% rising to >70% in patients with HbA1c <7.3%.

About Metformin

Metformin is from a class of drugs known as Biguanides. These work in two ways. They help to stop the liver producing new glucose and it also overcomes insulin resistance by making insulin carry glucose into muscle and fat cells more effectively. Metformin is the only drug that has shown demonstrable cardiovascular benefit in type 2 diabetes and is the established first-line treatment in the UK.

About repaglinide [PRANDIN®]

Repaglinide [PRANDIN®] has a distinct mode of action that targets post prandial glucose (PPG) i.e. glucose in the blood after meals, and is therefore known as a Post-Prandial Glucose Regulator. It works by stimulating the pancreas to produce more insulin only when glucose levels are elevated and is therefore to be taken at times when a meal is consumed. PRANDIN acts on a specific receptor site of the Beta cell of the pancreas, Kir6.2/SUR1 distinct from that of sulphonylureas and does not stimulate insulin secretion between meals. In this way they are shorter acting than sulphonylureas and therefore present a lower risk of hypoglycaemia and avoid the need for between meal snacking.

About Sitaglitptin

Sitagliptin is a new type of medication from a new class of drugs called 'DPP-4 (dipeptidyl peptidase- 4) inhibitors'. It works by blocking the action of the enzyme, DPP-4, which destroys the hormone incretin. Incretins help the body produce more insulin only when it is needed and reduce the amount of glucose being produced by the liver when it is not needed. These hormones are released throughout the day and levels are increased at meal times.

About DAIICHI SANKYO

Through the merger of two major pharmaceutical companies with Japanese origin, completed in April 2007, DAIICHI SANKYO UK LTD has strengthened its position as the number one pharmaceutical company in Japan and the 19th largest pharmaceutical company in the world. As a global pharma innovator, the business strategy is to focus on the company's research activities to develop and commercialise innovative medicines.

DAIICHI SANKYO UK LTD moved to a brand new office in Gerrards Cross, Buckinghamshire during June 2006 to provide much-needed space and facilities to continue building the UK business in the future. The current UK product range is focused on the treatment of cardiovascular diseases and diabetes.

In addition, DAIICHI SANKYO UK LTD has located their European Research & Development Division in the same office building. This demonstrates the importance of the UK in the company's global clinical development programme.

Daiichi Sankyo Facts

- Largest pharmaceutical company in the Japanese market
- First company to develop a statin for hyperlipidaemia
- First company to develop a glitazone for diabetes
- £4.6 billion of worldwide net sales
- 18.4% global net sales invested in R&D
- One of the 20 leading global pharmaceutical companies
- 15,400 employees around the world; 1,800 in Europe of which 150 are in the UK

http://www.daiichi-sankyo.co.uk