New Data Show Direct Targeting of Insulin Resistance with Combination Therapy Achieves Positive Effects on Blood Glucose and Cardiovascular Risk

New data presented for the first time at the 40^th Annual Meeting of the European Association for the Study of Diabetes (EASD) demonstrate that insulin resistance is an independent risk factor for cardiovascular disease in its own right ¹. Complementing this, further new data show that the treatments metformin and rosiglitazone in combination (AVANDAMET) effectively control blood glucose and offer blood pressure lowering benefits ². Experts suggest that through targeting insulin resistance in Type 2 diabetes directly with insulin sensitisers, positive effects on blood glucose and cardiovascular risk factors can be expected.

Commenting on the findings, Dr Minesh Patel, a Sussex-based GP with an interest in diabetes, said: “We know that cardiovascular disease is a significant threat in the longer term for those patients with Type 2 diabetes, and a root cause of both is insulin resistance. These new data demonstrate that we must start to focus on the long term by targeting the underlying pathology early in disease development. The Rosak data show that, by targeting insulin resistance with combination therapy in Type 2 diabetes, we can provide effective blood glucose control whilst having positive effects on blood pressure. This is important and could help us to ease the future impact of the disease.”          

Analysis of 1,179 patients without Type 2 diabetes confirmed that an increase in insulin resistance was associated with an increased prevalence of cardiovascular disease ¹; this is similar to the relationship seen amongst patients with Type 2 diabetes ³.  The authors conclude that it is at least as important to address insulin resistance as it is to target conventional risk factors for cardiovascular disease such as high blood pressure.

Additional pooled data from two six-month, real-life, observational studies involving 11,014 patients who received rosiglitazone and metformin in combination, demonstrated that patients can achieve their blood glucose targets and also benefit from blood pressure lowering ². The proportion of patients with HbA _1c < 6.5% (IDF goal) and < 7.0% (ADA goal) increased from 5% and 14% at the start to 39% and 64% at the end of the observational period ². Mean blood pressure decreased from 144/85 mmHg to 137/82 mmHg ² (clinicians were able to vary anti-hypertensive medications in these real-life, observational studies).

The association between insulin resistance and cardiovascular disease is as strong as that seen for smoking ³ and it is the cause of death for almost three quarters of those with Type 2 diabetes ⁴. Research by Saydah et al shows that 63% of patients are still unable to achieve target HbA _1c level of less than 7.0% ⁵ .

Agents that address insulin resistance (insulin sensitisers) demonstrate both long term glycaemic control⁶ and positive effects on a range of cardiovascular risk factors⁷ ; they are the logical early addition to metformin monotherapy, or as combination.

Notes

About Type 2 diabetes and insulin resistance

1.   Type 2 diabetes is an inability to process glucose properly due to a combination of genetic and environmental factors, particularly obesity. This leads to insulin resistance and ultimately, after a number of years, the body will fail to produce enough insulin for the body’s needs.

2.   Type 2 diabetes is a progressive illness that can lead to serious long-term complications, such as heart disease, stroke, blindness and kidney failure.

About rosiglitazone plus metformin

1.    A combination of rosiglitazone and metformin, AVANDAMET (rosiglitazone / metformin HCl), is indicated for the treatment of Type 2 diabetes, particularly in overweight patients, unable to achieve sufficient glycaemic control at their maximal tolerated dose of metformin alone.

2.   Rosiglitazone is also indicated as oral monotherapy for the treatment of Type 2 diabetes, particularly in overweight patients, inadequately controlled by diet and exercise for whom metformin is inappropriate because of contraindications or intolerance.

3.  Kirpichnikov D, Sowers JR, Diabetes mellitus and diabetes-associated vascular disease. Trends in Endocrinology and Metabolism 2001; 12: 225-230

References

1.   Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 2004;291:335-342.

8.    Pagano E et al.  Pharmacoeconomics 1999; 15 (6): 583-595

10.  Kobayashi M. Diabetes Obes Metab 1999; 1: S32-S40

13.  Virtanen KA et al. Different effects of rosiglitazone and metformin on adipose tissue glucose update in Type “ diabetes. Diabetologia 2002; EASD: P780

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Gluco-forum to Tackle Pre-Diabetes in Europe

Despite the sustained efforts worldwide to combat the diabetes epidemic, urgent action is needed to address the condition earlier, at the "pre-diabetes" stage. A survey by Gluco-forum, a new group of diabetes specialists, set up by the International Diabetes Federation (IDF) European Region, reveals that 69% of people across Europe still feel that Governments, doctors and nurses should be doing more to manage the problem of pre-diabetes therefore preventing people developing diabetes at all. Gluco-forum has been formed to actively help the 60 million people in Europe thought to be most at risk of pre-diabetes. Its foundation coincides with the European Association for the Study of Diabetes (EASD) Annual Meeting - 5th-9th September.

The European survey(1) on public awareness and understanding of pre-diabetes is the first of Gluco-forum's activities. The full findings of the survey, conducted across UK , France , Germany , Italy and Spain with over 2,000 people, will be released shortly in advance of World Diabetes Day, November 2004.

Pre-diabetes is a metabolic condition characterised by insulin resistance and primary or secondary beta cell dysfunction, factors which increase the risk of developing type 2 diabetes. It is estimated that over 50% of people with pre-diabetes will develop diabetes within five years. Those people thought to be most at risk of pre-diabetes tend to have a family history of diabetes, high blood pressure, high cholesterol and/or be overweight.

Dr Michael Hall, Chair of Gluco-forum and Board Member of IDF European Region, says: "There's so much talk about preventing diabetes, action is now the key to saving lives."

"By the time type 2 diabetes is diagnosed, 50% of these people will already have cardiovascular and kidney complications. Structured lifestyle change is currently the accepted management approach for pre-diabetes, but it is generally difficult for individuals to adhere to the advice in the real world(2). A number of clinical studies have also shown that drug therapy can reduce the incidence of diabetes."

"Whilst keeping abreast of new treatment approaches, Gluco-forum will raise awareness to prediabetes throughout Europe and provide practical materials to help people help themselves as well as ensuring doctors and nurses are well-informed", Dr Hall concluded.

Gluco-forum is the first educational initiative not only to focus on the subject of 'pre-diabetes' across Europe , but also to bring patient association representatives together with doctors and nurses in this context to tackle diabetes prevention.

References:

1. An in-home survey carried out with 2,226 adults over the age of 45, conducted by Ipsos Health in June 2004 on behalf of Gluco-forum

2. Zimmet P, Shaw J, Alberti KG. Preventing Type 2 diabetes and the dysmetabolic syndrome in the real world: a realistic view. Diabet Med 2003 Sep;20(9):693-702

(8/9/04)