The recent emergence of effective anti-obesity medications, including the recent approval of tirzepatide by the U.S. Food and Drug Administration, raises the question of whether weight loss, rather than glucose control, should now be considered the primary target for intervention in type 2 diabetes.
A pair of experts debated that question on Saturday, June 4, during the Current Issues session Weighing the Evidence—Should Obesity Be the Primary Target of Treatment in Type 2 Diabetes? The session was livestreamed and can be viewed on-demand by registered meeting participants at ADA2022.org. If you haven’t registered for the 82nd Scientific Sessions, register today to access the valuable meeting content.
Ildiko Lingvay, MD, MPH, MSCS, Professor of Medicine in the Department of Internal Medicine and the Department of Population and Data Sciences at the University of Texas Southwestern Medical Center, argued in favor of obesity as the primary treatment target.
“Obesity is a major driver of the pathophysiology of type 2 diabetes, and weight gain further promotes diabetes progression and is associated with worse glycemic control,” she said. “Effectively and proactively addressing obesity in our patients with type 2 diabetes has benefits that extend well beyond glycemic control. It improves the overall health of our patients and represents a holistic approach to a complex disease. So, I would argue that a target of 15% weight loss is the new 7% A1C in type 2 diabetes.”
Obesity, or adiposity, promotes the two core defects of diabetes, she said, insulin resistance and beta-cell decompensation.
“But that is just part of the picture—it gets a lot more complicated,” Dr. Lingvay said. “Because, through other mechanisms that adiposity fuels—like sleep disorders, fatigue, and mental health issues—it additionally fuels the diabetes. There’s an inverse relationship as well, as diabetes causes many complications that further fuel the adiposity and ultimately creates a vicious cycle pushing forward the disease process.”
Dr. Lingvay cited numerous studies that have demonstrated the benefit of weight loss in preventing the progression from prediabetes to diabetes. In some cases, diabetes remission is possible. But when treating patients, she said it’s important to remember that body mass index (BMI) does not equal obesity.
“It’s really about the amount of weight that somebody carries, the abnormal distribution of this weight, and its function,” she said. “Whenever these exceed the personal threshold of a person, that’s when this becomes a medical condition with clinical consequences. Don’t just go by BMI.”
Arguing the opposing view, Jeffrey I. Mechanick, MD, Professor of Medicine and Director of Metabolic Support in the Division of Endocrinology, Diabetes, and Bone Disease at the Icahn School of Medicine at Mount Sinai, said the debate is more a question of semantics than science.
Glucose control, he said, may no longer be considered “the” primary target in the treatment of type 2 diabetes, but it certainly remains “a” primary target.
“Rather than stipulating that primary targets are mutually exclusive—weight or glucose—we should think about weight loss and glucose as part of a comprehensive care plan that addresses multiple chronic disease drivers,” Dr. Mechanick said. “Indeed, there are multiple primary targets—adiposity, dysglycemia, and other cardiometabolic risk factors—that can be prioritized based on relative risks, logistical ease, cost, and individual factors. Primary targets can be addressed concurrently, not necessarily sequentially.”
Future discussions, he said, should center on codifying risks, attributing priorities based on relevant outcomes, and designing evidence-based strategies and tactics to optimize these outcomes, all within a comprehensive preventive care plan.
“Optimal type 2 diabetes care is individualized, and glucose control is a necessary, but not sufficient, primary target in patients with type 2 diabetes to prevent the development and progression of complications,” Dr. Mechanick said.