Meeting News CoveragePerspective

Obesity treatment paradigms should target those at risk for diabetes

PHOENIX — Lifestyle modifications, weight-loss medications and bariatric surgery are the three major modalities that will have clinical implications on the prevention and treatment of obesity, according to data presented here.

“With effective options in all of these three treatment modalities, we can now evolve rational data-driven models of care that treat obesity as a medical illness,” W. Timothy Garvey, MD, professor and chair in the department of nutrition sciences at the University of Alabama at Birmingham, and senior scientist at the Nutrition Obesity Research Center, told Endocrine Today.

W. Timothy Garvey, MD 

W. Timothy Garvey

Emerging therapies

During a presentation on emerging obesity therapies, Garvey reported recent data on phentermine-topiramate (Qsymia, Vivus) and lorcaserin (Belviq, Eisai), both of which gained approval in adults with an initial BMI of at least 30 or in those with a BMI of at least 27 and at least one weight-related condition, such as hypertension, type 2 diabetes or dyslipidemia.

“We’re in an exciting phase of drug development for obesity, with two drugs approved in the summer of 2012 that appear to be safe and effective for the treatment of obesity,” Garvey said.

“In addition, we have two other drugs that have finished or will soon finish phase 3 trials.”

One of these is bupropion/naltrexone (Contrave, Orexigen), an experimental agent now finished with phase 3 clinical trials. According to Garvey, a cardiovascular outcomes study is currently ongoing as requested by the FDA before approval. “The BP did not increase with the drug, but it didn’t go down to the extent that you’d predict with the weight loss achieved,” he said. “This will be the first cardiovascular outcomes study with a weight-loss drug where the data will be available in, perhaps, 2014.”

About an 8% weight loss was demonstrated and sustained during 1 year compared with 2% with placebo, Garvey said.

Furthermore, he referenced recent data from a 56-week, double blind, phase 3a clinical trial investigating higher-dose liraglutide (Victoza, Novo Nordisk) as a potential treatment for maintained weight loss in overweight or obese patients with type 2 diabetes. The manufacturer recently released the second phase 3a trial results from the clinical development program for liraglutide 3 mg as an obesity treatment.

“About 4 kg were lost on lifestyle intervention alone, and up to 9 kg were lost with high-dose liraglutide. There are 2-year data indicating that its efficacy for sustaining this weight loss is evident,” Garvey said.

Bariatric surgery

However, Garvey said medical and surgical interventions provide the best outcomes in obese patients with complications, and optimal benefit–risk occurs when weight loss is used as a tool to treat these complications of obesity.

As an adjunct to lifestyle modification, the aforementioned new medical therapies can result in a 10% loss of body weight, but if a patient begins with a BMI of 38, he will likely be obese when therapies are complete, Garvey said.

“However, that 10% loss of body weight is sufficient to improve insulin sensitivity, glucose homeostasis, lipid levels, BP, diabetes prevention, CVD risk factors and better control of both glucose and BP in patients with type 2 diabetes. We’re achieving an amount of weight loss here that’s in fact beneficial in terms of cardiometabolic disease,” he said.

Moving forward

Garvey concluded with the economic burden of diabetes and obesity on the United States health care system. He told Endocrine Today that for the clinical research community to address the diabetes and obesity epidemics, the progression from prediabetes to diabetes should first be considered.

“A rational and effective obesity treatment paradigm that targets resources to patients who are at highest risk will be cost-effective in preventing diabetes,” he said. “The numbers vary, but it costs much more per year to take care of a patient with diabetes than it does to take care of a patient without diabetes.”

Garvey said if new paradigms of treatment are going to be introduced, researchers and clinicians should be mindful of the health economics, which can be achieved using the new AACE algorithm’s complication-centric model.

“If we can prevent the progression of diabetes, we’re going to need to increase public health awareness and decrease the social burden and cost of these diseases,” he said. – by Samantha Costa

For more information:

Garvey WST. SGS6: New and emerging drugs for managing obesity. Presented at: the AACE Annual Scientific and Clinical Congress; May 1-5, 2013; Phoenix.

Disclosure: Garvey reports research funding from Amylin, Merck and Weight Watchers, and being on advisory board panels for Aquinox, Daiichi-Sankyo, Janssen, Tethys Bioscience and Vivus.

PHOENIX — Lifestyle modifications, weight-loss medications and bariatric surgery are the three major modalities that will have clinical implications on the prevention and treatment of obesity, according to data presented here.

“With effective options in all of these three treatment modalities, we can now evolve rational data-driven models of care that treat obesity as a medical illness,” W. Timothy Garvey, MD, professor and chair in the department of nutrition sciences at the University of Alabama at Birmingham, and senior scientist at the Nutrition Obesity Research Center, told Endocrine Today.

W. Timothy Garvey, MD 

W. Timothy Garvey

Emerging therapies

During a presentation on emerging obesity therapies, Garvey reported recent data on phentermine-topiramate (Qsymia, Vivus) and lorcaserin (Belviq, Eisai), both of which gained approval in adults with an initial BMI of at least 30 or in those with a BMI of at least 27 and at least one weight-related condition, such as hypertension, type 2 diabetes or dyslipidemia.

“We’re in an exciting phase of drug development for obesity, with two drugs approved in the summer of 2012 that appear to be safe and effective for the treatment of obesity,” Garvey said.

“In addition, we have two other drugs that have finished or will soon finish phase 3 trials.”

One of these is bupropion/naltrexone (Contrave, Orexigen), an experimental agent now finished with phase 3 clinical trials. According to Garvey, a cardiovascular outcomes study is currently ongoing as requested by the FDA before approval. “The BP did not increase with the drug, but it didn’t go down to the extent that you’d predict with the weight loss achieved,” he said. “This will be the first cardiovascular outcomes study with a weight-loss drug where the data will be available in, perhaps, 2014.”

About an 8% weight loss was demonstrated and sustained during 1 year compared with 2% with placebo, Garvey said.

Furthermore, he referenced recent data from a 56-week, double blind, phase 3a clinical trial investigating higher-dose liraglutide (Victoza, Novo Nordisk) as a potential treatment for maintained weight loss in overweight or obese patients with type 2 diabetes. The manufacturer recently released the second phase 3a trial results from the clinical development program for liraglutide 3 mg as an obesity treatment.

“About 4 kg were lost on lifestyle intervention alone, and up to 9 kg were lost with high-dose liraglutide. There are 2-year data indicating that its efficacy for sustaining this weight loss is evident,” Garvey said.

Bariatric surgery

However, Garvey said medical and surgical interventions provide the best outcomes in obese patients with complications, and optimal benefit–risk occurs when weight loss is used as a tool to treat these complications of obesity.

As an adjunct to lifestyle modification, the aforementioned new medical therapies can result in a 10% loss of body weight, but if a patient begins with a BMI of 38, he will likely be obese when therapies are complete, Garvey said.

“However, that 10% loss of body weight is sufficient to improve insulin sensitivity, glucose homeostasis, lipid levels, BP, diabetes prevention, CVD risk factors and better control of both glucose and BP in patients with type 2 diabetes. We’re achieving an amount of weight loss here that’s in fact beneficial in terms of cardiometabolic disease,” he said.

Moving forward

Garvey concluded with the economic burden of diabetes and obesity on the United States health care system. He told Endocrine Today that for the clinical research community to address the diabetes and obesity epidemics, the progression from prediabetes to diabetes should first be considered.

“A rational and effective obesity treatment paradigm that targets resources to patients who are at highest risk will be cost-effective in preventing diabetes,” he said. “The numbers vary, but it costs much more per year to take care of a patient with diabetes than it does to take care of a patient without diabetes.”

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Garvey said if new paradigms of treatment are going to be introduced, researchers and clinicians should be mindful of the health economics, which can be achieved using the new AACE algorithm’s complication-centric model.

“If we can prevent the progression of diabetes, we’re going to need to increase public health awareness and decrease the social burden and cost of these diseases,” he said. – by Samantha Costa

For more information:

Garvey WST. SGS6: New and emerging drugs for managing obesity. Presented at: the AACE Annual Scientific and Clinical Congress; May 1-5, 2013; Phoenix.

Disclosure: Garvey reports research funding from Amylin, Merck and Weight Watchers, and being on advisory board panels for Aquinox, Daiichi-Sankyo, Janssen, Tethys Bioscience and Vivus.

    Perspective

    George Grunberger, MD, FACP, FACE 

    George Grunberger

    The presentation was phenomenal. The issue of obesity in conjunction with introducing our AACE algorithm really should put us on the center stage regarding the obesity debate. The main point Garvey was driving was the discrepancy of the politics of obesity based on BMI measurements. BMI is a nice surrogate for obesity but has nothing to do with the benefits or risks of treatment. The question now is how do we convince the regulators or the payers to pay for treatment for obesity in patients who are most likely to benefit? To me it seems logical.

    • George Grunberger, MD
    • Clinical professor of internal medicine and of molecular medicine and genetics Wayne State University School of Medicine

    Disclosures: Grunberger reports research grants from Bristol-Myers Squibb, Lilly, Novo Nordisk and speakers’ bureau fees from Amarin, Lilly, Merck, Novo Nordisk, Sanofi, Takeda and Valeritas.

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