OncologyPromising Results With Aleglitazar, A New Treatment Drug For Type 2 Diabetes (SYNCHRONY Study)
The results from the phase II SYNCHRONY study are published in an article Online First and in a future edition of The Lancet. At the same time, the findings are presented at the American Diabetes Association meeting in New Orleans, USA. They suggest that aleglitazar, a treatment for type 2 diabetes, might be safe and effective and may perhaps be introduced into phase III trials.
Aleglitazar belongs to a class of drug called PPAR co-agonists. It can have an effect on both glucose and fat (lipid) control. This drug is also comparable in function to rosiglitazone and pioglitazone, which are part of the thiazolidinedione family of drugs. Both of these drugs are accepted as efficient agents for blood glucose control in patients with type 2 diabetes. However, there is safety concern related to their use, such as a higher risk in heart failure. Due to harmful effects, several co-agonists drugs have been discontinued. Professor Robert R Henry, of the University of California, San Diego, USA, and collaborators are the authors of SYNCHRONY. They are confident about the promising effects of aleglitazar on glucose control, excluding the associated safety issues.
Patients were enrolled from forty four different places in seven countries in order to participate in this phase II randomised study. They were all patients with type 2 diabetes, either not receiving any drug or treated with up to two oral agents. During five weeks, they all received placebo. Then the 332 patients were given treatment at random during sixteen weeks with aleglitazar with once-a-day doses of 50, 150, 300, 600 áµg, or matching placebo (55 in each group), or with pioglitazone 45 mg once daily (57 patients) as a reference. The change in glycosylated haemoglobin concentration (HbA1c) from baseline to the end of treatment was the main endpoint. HbA1c is used to indicate the average plasma glucose concentration of the preceding two to three months. In general, the reference range that is found in healthy persons who do not have diabetes is about 4 to 5.9 percent. Patients with diabetes usually have HbA1c levels above 6.5 percent.
Research showed that aleglitazar reduced baseline HbA1c versus placebo in a dose-dependent way (from -0.36 percent with 50 áµg to -1.35 percent at 600 áµg). After evaluating the trend of change over time, the researchers found that the maximum effect of aleglitazar on HbA1c concentration was not yet reached following sixteen weeks of treatment. There were side effects linked to the drug quantity, such as oedema, haemodilution, and weight gain.
When giving aleglitazar in doses inferior to 300 áµg, there were no reports of congestive heart failure, the incidence of oedema (two cases at 150 áµg) was less than placebo (three cases), and also less than with pioglitazone (four cases). In addition, with a dose of 150 áµg, bodyweight gain was less than half (0.52 kg) than with pioglitazone (1.06 kg).
The authors explain: "Importantly, aleglitazar seemed to be safe and well tolerated over the course of the 16-week study. The sample size of this study was too small to make definitive conclusions, but that no heart attack or stroke events occurred is reassuring. By contrast, excess cardiovascular events have been noted for patients given muraglitazar and rosiglitazone after a fairly short exposure to treatment."
They write in conclusion: "The favourable balance in the safety and efficacy profile of aleglitazar represents encouraging short-term clinical data for this agent and provides good evidence to enter phase III investigation."
They remark: "It will be particularly interesting to see whether the combined beneficial glucose and lipid effects will translate into a benefit on cardiovascular outcomes."
In a supplementary note, Dr Bernard Charbonnel, of the Institut du Thorax, University of Nantes, France, remarks: "The balance of safety and efficacy in today"s paper is encouraging, but it is impossible to draw definitive clinical conclusions from such a phase II study. Experience with muraglitazar has shown that a good lipid and blood glucose profile is not sufficient to predict clinical outcomes. It is a strength that cardiovascular events, including heart failure, were adjudicated in SYNCHRONY (two cases of heart failure, no heart attacks), but the sample size and short duration of the study do not allow firm conclusions."
He says in closing: "Research in this difficult area must be encouraged, and the coming years will tell whether hopes raised by the SYNCHRONY study for aleglitazar are confirmed by appropriate long-term clinical trials."
"Effect of the dual peroxisome proliferator-activated receptor-í±/í³ agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study"
Robert R Henry, A Michael Lincoff, Sunder Mudaliar, Michael Rabbia, Cathy Chognot, Matthias Herz
DOI: 10.1016/S0140-6736(09)60870-9
thelancet
Written by Stephanie Brunner (B.A.)
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today