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New combination therapy is game-changer in treatment of type 2 diabetes

September 11, 2014

Adverse effects of the current drug treatments for patients with type 2 diabetes, such as weight gain and low blood sugar levels, could be virtually eliminated by adopting a treatment strategy that is proving effective and safe in clinical trials worldwide, according to a study published today in The Lancet.
An analysis of current research led by investigator Dr. Ravi Retnakaran of Mount Sinai Hospital in Toronto, Canada shows that, when combined with long-acting insulin, a new class of medication that mimics a naturally occurring gut hormone can obtain excellent blood sugar control – without increased risk of low sugars or weight gain.
"The ability to achieve this ideal trifecta – glucose control, plus weight loss and no increased risk of low sugars or weight gain – offers the opportunity to change the paradigm of clinical management for type 2 diabetes," notes Dr. Retnakaran.
The hormone (glucagon-like peptide-1 agonist, or GLP-1 agonist) is produced in the gut as part of normal digestion. It is triggered by the presence of food in the small intestine, and acts almost instantly and with exquisite sensitivity to fine-tune the balance of insulin to blood sugar. Combining a GLP-1 agonist with long-acting insulin gives better blood glucose control and induces weight loss, with no increased risk of low sugars, as compared to other anti-diabetic therapies.
In type 2 diabetes, the body's ability to produce insulin and effectively metabolize sugar decreases over time. To control their blood sugar levels, patients typically are treated with different medications, and many ultimately need insulin itself. With current drugs and even with insulin treatment, however, many patients are not able to reach target levels for blood sugar control, experiencing increased risks of low blood sugar and weight gain.     
The research team's meta-analysis and systematic review examined 15 recent randomized controlled trials, which involved a total of 4,348 participants. Based on the study's results, the research team at Mount Sinai Hospital is currently starting a new clinical trial (called PREVAIL) of this combination therapy.   
"The closer we are to mimicking normal blood glucose control, the better for patients with diabetes," notes Dr. Jim Woodgett, Director of the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital. "This study should provide the impetus to change standards of care to benefit everyone with this disease."
The new treatment protocol is not the only advance in type 2 diabetes, Dr. Retnakaran adds. "We are also seeing big gains in using insulin alone for short periods in the early stages of type 2 diabetes, rather than reserving it as a 'rescue' medication for later in the disease. Using insulin early and for only a few weeks at a time is another strategy for obtaining excellent blood sugar control without weight gain or increased risk of low blood sugars." His team is testing this strategy in a clinical trial at Mount Sinai Hospital (Toronto) called RESET IT.
Dr. Retnakaran is an Investigator at Mount Sinai Hospital's Lunenfeld-Tanenbaum Research Institute and an endocrinologist at the hospital's Leadership Sinai Centre for Diabetes, in Toronto, Canada. He is an Associate Professor in the Division of Endocrinology and Metabolism at University of Toronto.
The study is "Glucagon-like peptide-1 receptor agonist and basal insulincombination treatment for the management of type 2 diabetes: a systematic review and meta-analysis."  The authors are Conrad Eng and Drs. Caroline K. Kramer, Bernard Zinman, and Ravi Retnakaran. All are based at Leadership Sinai Centre for Diabetes, Mount Sinai Hospital (Toronto, Canada), where Drs. Retnakaran and Zinman are investigators in the Lunenfeld-Tanenbaum Research Institute. Funders and supporters include Canadian Diabetes Association, Heart & Stroke Association of Ontario, Ontario Ministry of Research and Innovation, and Mount Sinai Hospital Foundation.
Diabetes leadership: Researchers at Mount Sinai Hospital (Toronto) have contributed to three of the four most prescribed diabetes medications in the world. The hospital's Lunenfeld-Tanenbaum Research Institute is ranked Number 1 in citations for diabetes research among institutes worldwide. As well, the hospital's internationally recognized physicians receive more than 20,000 diabetes patient visits each year at the Leadership Sinai Centre for Diabetes, Canada's referral centre for the most difficult and complex diabetes cases.

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