42nd Annual Meeting of the European Association for the Study of Diabetes

Rosiglitazone found to reduce progression from impaired glucose metabolism to diabetes
In the largest diabetes prevention trial ever conducted, rosiglitazone was linked to a reduced risk of developing type 2 diabetes in people with pre-diabetes.

The Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study evaluated the likelihood of progression to type 2 diabetes over a 3-year median follow-up period among 5269 people with impaired fasting glucose or impaired glucose tolerance.

Participants were randomised to rosiglitazone (8 mg daily) or placebo and to ramipril (15 mg daily) or placebo – in a 2-by-2 factorial design – and were assessed every 6 months for 3–5 years to determine if rosiglitazone or ramipril led to a decrease in the incidence of type 2 diabetes.

Rosiglitazone reduced the risk of developing type 2 diabetes by 62% (P<0.0001) relative to placebo. The reduction was additive to standard counselling on healthy eating and exercise.

Ramipril did not significantly reduce the risk of diabetes, which was developed by 18% of participants on that drug and 20% on placebo.

Dr Hertzel Gerstein, Co-principal Investigator and a Professor of Medicine at McMaster University, Canada, said the results have major implications for future health care. ‘If we can prevent diabetes, we may also be able to prevent the serious cardiovascular, eye, kidney, and other health consequences of diabetes,’ he stated. ‘The DREAM results show that adding rosiglitazone to healthy lifestyle advice substantially lowers the chance of getting diabetes in people at high risk for the disease.’

‘The world is facing a major diabetes epidemic,’ said Professor Rury Holman, European Co-chair of DREAM and a Professor of Diabetic Medicine at University of Oxford. ‘The knowledge that rosiglitazone can reduce the risk of people developing diabetes provides another opportunity to help tackle this growing healthcare problem.’

‘Diabetes dramatically increases the risk of cardiovascular and other problems’ said Dr Salim Yusuf, Co-principal Investigator and a Professor of Medicine at McMaster University. ‘Although ramipril did not prevent diabetes, the beneficial metabolic effects that we found may add to the clinical benefits of ACE inhibitors seen in HOPE and other studies.’

The DREAM study was conducted by the Population Health Research Institute at the Michael G DeGroote School of Medicine at McMaster University and Hamilton Health Sciences in Hamilton, Ontario.

DREAM was funded by a peer-reviewed grant from the Canadian Institutes of Health Research, as well as by GlaxoSmithKline, Sanofi-aventis and King Pharmaceuticals.

Liraglutide boosts insulin secretion
Liraglutide, an investigational treatment for type 2 diabetes, improved the ability of pancreatic beta-cells to secrete insulin in people with type 2 diabetes, according to data presented at the conference.

The findings of this sub-study were from a larger randomised controlled trial conducted over 14 weeks. The main trial showed that liraglutide reduced levels of HbA_1c.

Liraglutide (a glucagon-like peptide-1 analogue) is currently in phase 3 clinical trials.

HbA_1c effect: Exenatide  matches insulin
Results released at the conference from two open-label studies showed that exenatide (a glucagon-like peptide-1 analogue) is as effective as insulin glargine and biphasic insulin aspart at reducing HbA_1c levels in people with type 2 diabetes who were not deemed to have acceptable blood glucose control on metformin, a sulphonylurea or both.

Exenatide has been submitted to the European Agency for the Evaluation of Medicinal Products for approval in the EU.

ESC and EASD announce joint guidelines on diabetes and CVD
The European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) have developed the first evidence-based guidelines covering both diabetes and cardiovascular disease (CVD). The news was announced by a group including Professor Ele Ferrannini, President of the EASD (key messages are below).

Fourteen experts from all over Europe were assigned to draft manuscripts, according to their specific area of expertise. The guidelines were then formulated and reviewed by 18 experts from the ESC and EASD. Approximately 1500 comments and suggestions were dealt with by the writing group.

There are a total of 72 recommendations. A full text, including 711 references, will appear on the website www.escardio.org. Pocket guidelines will also be produced in the near future.

These guidelines will complement the joint American Diabetes Association and EASD consensus algorithm, developed for the treatment of type 2 diabetes [Nathan DM et al (2006) Diabetologia 49(8): 1711–21]. Nathan et al acknowledge that while diet and exercise are undoubtedly beneficial in the control of the condition, these lifestyle interventions alone often fail to achieve or maintain long-term metabolic goals. They suggest that metformin therapy should be initiated concurrent with lifestyle intervention at diagnosis. However, this is unlicensed and metformin is currently only indicated for type 2 diabetes mellitus, particularly in overweight patients, when diet and exercise alone do not result in adequate glycaemic control.

Key messages:

1. Diabetes and CVD are much more common than imagined.
2. The negative impact of dysglycemia is apparent before the onset of diabetes.
3. The prognosis is principally amenable to major progress, yet still unfavourable.
4. An investigational algorithm needs to be employed to detect the alternate side of the disease either starting from diabetes or from coronary artery disease.
5. An oral glucose tolerance test is the best method to diagnose previously unknown diabetes or pre-diabetes,
6. To minimise resources, primary screening for the potential of diabetes can be effectively done by a non-invasive risk score to define high risk.
7. Prevention both of diabetes and CVD is possible.
8. Therapeutic success depends on collaboration across speciality borders.
9. Treatment comprises multifactorial risk intervention and targeted management of CVD.
10. Structured lifestyle counselling is a very important therapy for these patients and needs to be improved.
11. Targets for treating blood pressure, blood glucose and lipids have been defined and are more strict than before.
12. The joint ESC/EASD approach provides the state-of-the-art evidence base.

Effects of insulin glargine similar in group and individual initiation
Results from the INITIATE study released at the conference demonstrate that initiating insulin glargine in people with type 2 diabetes provided similar glycaemic control at 24 weeks following group and individual sessions (mean HbA_1c of 6.8% [reduced from 8.8%] and 6.9% [reduced from 8.7%], respectively).

In addition, the two methods of insulin initation had similar effects on treatment satisfaction.

INITIATE is a mulitcentre, randomised, open-label trial. One hundred and twenty people who were uncontrolled on maximal doses of oral hypoglycaemic agents entered the study.

Accu-Chek data tools may improve clinical outcomes
Two new data management and advice tools developed for people on insulin may significantly improve clinical outcomes, suggested study results released at the conference.

One tool is the Accu-Chek Pocket Compass Software, which is primarily used by people with external insulin pumps. The other is the Accu-Chek Advisor Insulin Guidance Software, which is still in the test phase.

Burkhard G Piper, Head of Diabetes Care at Roche Diagnostics, commented that the ‘advice tools translate collected data into an actionable context and close the circle of care in diabetes management by bridging the gap between glucose monitoring and therapy.’

Exubera shows efficacy in people developing respiratory infections
Adults with diabetes who used Exubera inhaled insulin were able to safely maintain good blood glucose control even if they developed a respiratory infection or were exposed passively to cigarette smoke. These findings were presented at the conference.

In addition, according to a retrospective analysis of 14 phase 2 and 3 clinical studies, Exubera was deemed to be well tolerated and efficacious, even during respiratory illness in adults with type 1 or type 2 diabetes.

Another new study found that while passive smoke exposure could result in decreased absorption, Exubera could be used by people with diabetes who were exposed to a smoky environment.

‘This information is important for healthcare providers who have prescribed or are considering prescribing Exubera to their patients,’ said Professor Philippe Camus, Lead Investigator from the University Medical Center, Dijon, France. ‘It shows that the efficacy and tolerability of Exubera remain unchanged even if patients develop a cold or the flu.’