44th Annual Meeting of the European Association for the Study of Diabetes

UKPDS 30-year results show that good glucose control needed from diagnosis of type 2 diabetes
On Wednesday 10 September, researchers from the Oxford Centre for Diabetes, Endocrinology and Metabolism presented 30-year results from the UKPDS (United Kingdom Prospective Diabetes Study).

The data illustrate the importance of achieving good blood glucose control from the point of diagnosis of type 2 diabetes in order to prevent complications such as retinopathy and nephropathy. They also indicate that tight control reduces cardiovascular risk and death in the long term.

The 1998 results of the UKPDS highlighted the benefits of intensive blood glucose control over “conventional” treatment in terms of preventing retinopathy and nephropathy. When the UKPDS finished, the participants returned to their usual health care, but continued to be monitored. The 10-year post-trial data presented at the meeting indicate that, while the blood glucose level differences between groups converged rapidly, the benefits of earlier intensive control on eye and kidney disease were maintained – a “legacy effect”. Statistically significant benefits also emerged in terms of reductions in myocardial infarction and mortality

“These results emphasise the importance of detecting and treating diabetes at the earliest opportunity and the major benefits that can be obtained with good blood glucose control,” commented Professor Rury Holman, the study’s Chief Investigator.

While the legacy effect was present in the blood glucose control arm, it was not observed in the blood pressure arm. The initial differences observed between the tight and less-tightly controlled groups disappeared early on into the follow-up period, with a converging in the risk of complications also occurring. These data indicate that it is important to continue with tight control of blood pressure in order to prevent complications.

The results of the UKPDS data were neatly summed up by Professor David Matthews, Oxford, who concluded: “With glucose control it matters how well you are treated now and how well you were treated in the past – with blood pressure it seems to be related just to current therapy, confirming how essential it is to maintain good blood pressure levels over time if the risk of complications is to be minimised.”

Phase 3 data confirm benefits of liraglutide in type 2 diabetes
Data from the LEAD 4 (Liraglutide Efficacy and Action in Diabetes) study were presented at the meeting, suggesting that the glucagon-like peptide-1 analogue liraglutide, when added to metformin and rosiglitazone, improves HbA_1c, reduces blood pressure, improves beta-cell functioning and leads to significant weight loss.

The study participants (n=553) were randomised to receive either once-daily liraglutide or placebo in addition to metformin and rosiglitazone. At baseline, the participants had a mean age of 55.1 years, a mean HbA_1c of 8.3%, and a mean BMI of 33.5kg/m².

After 26 weeks, liraglutide treatment yielded a 1.5 percentage point reduction in HbA_1c, with over half of the participants achieving an HbA_1c <7.0%, compared with just over a quarter on placebo (P<0.0001), with 35% of those taking liraglutide achieving an HbA_1c<6.5%. There were also statistically significant reductions in weight (P<0.0001) and blood pressure (P<0.001) in those taking liraglutide compared with placebo.

One of the most important findings was that liraglutide appeared to improve beta-cell function, as assessed by multiple parameters.

Vaccination for latent autoimmune diabetes in adults in development
Data presented at the conference indicate that vaccination with Diamyd (an isoform of glutamic acid decarboxylase [GAD]) can prevent the need for insulin therapy in people with latent autoimmune diabetes in adults (LADA).

The results show that treatment with Diamyd slows the loss of beta-cell function in people with LADA: only 14% of those who received the vaccination required insulin therapy after 5 years, compared with 64% of those in the placebo group.

Other data on the GAD isoform were also presented at the conference, and these indicated that the drug preserved insulin producing capacity in Swedish children and adolescents with type 1 diabetes over a 30-month period (P=0.04).

Sitagliptin: long-term safety and efficacy data
Results released on 9 September indicate that combination therapy with metformin and sitagliptin provides sustained improvements in blood glucose levels in people with type 2 diabetes over 2 years.

Alongside these data, results from a pooled analysis of 6139 individuals using 100mg sitagliptin daily showed that the drug was well-tolerated over 2 years.

In people taking sitagliptin 50mg in combination with metformin 1000mg (n=105), researchers observed a 1.7% reduction in HbA_1c from baseline over 2 years. For those receiving metformin at a dose of 500mg, the 2-year reduction in HbA_1c was 1.4%. Interestingly, people taking only sitagliptin 100mg once-daily had a reduction in HbA_1c of 0.8% after 1 year, rising to 1.2% after 2 years.

Further data that were presented indicate that sitagliptin provides consistent benefits in terms of glycaemic control for people with type 2 diabetes, regardless of age, gender and BMI.

Kamlesh Khunti, Professor of Primary Care Diabetes and Vascular Medicine, University of Leicester, believes that “these data are great news for physicians treating type 2 diabetes [and] it is reassuring to see longer-term tolerability data for this relatively new agent.”

Tight glycaemic control in older people may need reconsideration
Results from the VADT (Veterans Affairs in Diabetes Trial) comparing the effects of standard and intensive glucose control on eye and renal complications were presented, following the reporting of the macrovascular results at the American Diabetes Association’s Scientific Sessions earlier in the year.

There was no difference in hard eye endpoints between the standard and intensive treatment arms of the study; however, there was a trend towards a reduction in the proportion of patients experiencing early retinopathy in the intensive treatment arm (P=0.07).

There was a significant decrease in the progression from normal renal function to micro- or macroalbuminuria (P=0.02) favouring intensive glycaemic control, but differences were not observed for other renal measures.

The investigators concluded that the microvascular benefits of intensive glycaemic control may be less than expected in people where other risk factors are optimally controlled.

These data suggest that current standards for older people with diabetes may need to be revised to avoid endangering those who are intensively controlled.

Other Meetings
Diabetes institute for healthcare professionals opens in Paris
A new educational institute was officially opened in Paris on the 25 September to cover the Europe, Middle East and Africa region. Healthcare professionals can attend a complimentary diabetes education course at the institute, which is funded by Johnson & Johnson.

This institute is the fourth to open worldwide. Others were established in the US and Japan in 2007, and China earlier this year.

The institute is a non-promotional initiative designed to address the need for improved management of diabetes by working in collaboration with independent diabetes experts to deliver educational training and to support the efficient use of resources within diabetes care.

The training course focuses on innovative practice models and therapeutic patient education, placing the person with diabetes at the centre of all activities. One session involves using a video link to a “patient” to immediately implement what has just been taught.

The chairman of the institute,  Kenneth Moritsugu, has type 1 diabetes himself. His vision for the centres is that they might help diabetes professionals and their patients to move from “managing diabetes to mastering diabetes”.

Visit http://www.jjdi.eu to register with the institute and receive information about delegate opportunities.

Drug-eluting stents are safe in the long term
Three-year data from the Massachusetts stent registry were presented at the American Heart Association 2008 Scientific Sessions. The use of drug-eluting stents in a real-world population with diabetes was shown to have benefits in terms of reduced mortality, myocardial infarction (MI), and rates of revascularisation.

For the analysis, the researchers investigated data from more than 5000 people with diabetes, and used propensity-score matching to evaluate outcomes at 3 years in 1476 individuals treated with a drug-eluting stent, and 1476 treated with a bare-metal stent.

The analysis indicated that there were significantly lower rates of revascularisation among those treated with the drug-eluting stent (P<0.001). There were also benefits in terms of absolute mortality rates, which were 3.2% lower, and MI rates, which were 3.0% lower in the drug-eluting stent arm than the bare-metal stent arm (P=0.02).

The investigators believe that these data highlight the efficacy of drug-eluting stents observed in other trials, and suggest there are no increased safety concerns in long-term follow-up. Laura Mauri (Brigham and Women’s Hospital, Boston, MA) said: “I wouldn’t make a blanket statement, but, in general, there is great benefit to the use of drug-eluting stents in diabetic patients, and there does not appear to be a trade-off in terms of safety.”