Experts debate obesity vs. glycemic control as primary target for treating type 2 diabetes
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NEW ORLEANS — There is no single answer when it comes to determining the primary target for treating type 2 diabetes, two speakers said during a debate at the American Diabetes Association Scientific Sessions.
Promoting weight loss to improve health outcomes for people with type 2 diabetes is one of the targets emphasized in the 2022 ADA Standard of Care. Ildiko Lingvay, MD, MPH, MSCS, professor of medicine at University of Texas Southwestern Medical Center in Dallas, said obesity should be the primary target of treatment for type 2 diabetes; however, providers must focus on an individual’s phenotype and fat distribution instead of BMI.
“When you think of patients with type 2 diabetes, the majority are going to have adiposopathy,” Lingvay said during the presentation. “How do you identify them? Look at your patient in person. Where is their fat? How much do they have?”
Lingvay added that weight loss should be a goal concurrently with other applicable disease targets, something echoed by Jeffrey I. Mechanick, MD, professor of medicine, medical director at the Kravis Center for Clinical Cardiovascular Health at Mount Sinai Heart and director of metabolic support in the division of endocrinology, diabetes and bone disease at the Icahn School of Medicine at Mount Sinai. Mechanick said he agreed with Lingvay in that obesity should be a primary target for most with type 2 diabetes, but goals can vary based on an individual’s profile. Although not sufficient on its own, glycemic control should be another primary target considered by providers.
“There are multiple primary targets that are prioritized based on relative risk, logistical ease, cost and individual factors,” Mechanick said during the presentation. “Primary targets can be addressed concurrently, not necessarily sequentially and not necessarily mutually exclusive.”
Focus on obesity phenotype
Lingvay said obesity should be the primary target for treating type 2 diabetes, but providers should avoid using BMI to define the disease.
“It is all about fat quantity, quality and location,” Lingvay said. “I prefer to avoid the term obesity not just because our patients don’t like it, but because it is so intricately associated with BMI that it creates a problem when it comes to diagnosis.”
Much evidence supports the primary role of weight loss in glycemic improvement and reduced risks for diabetes-related complications and a reduced risk for other obesity-related conditions. In data from the Diabetes Prevention Program, participants reduced their risk for diabetes by 16% for each 1 kg of body weight lost. Findings from the Diabetes Remission Clinical Trial revealed most participants who achieved weight loss of 10 kg or more also reached type 2 diabetes remission, defined as having an HbA1c of less than 6.5% with no diabetes medications.
“The amount of weight loss is important, because the amount of weight loss correlated with the glycemic effect,” Lingvay said. “The benefits of weight loss are seen across the dysglycemic continuum.”
The amount of weight loss is crucial to maximizing benefits for people with diabetes. Lingvay said will achieve the most benefits, including diabetes remission and reductions in risks for dyslipidemia, hypertension, nonalcoholic fatty liver disease, heart failure and CVD. However, there is no single target for individual patients to hit. Lingvay noted the ADA Standard of Care emphasize coming up with an individualized target based on risks, disease duration, comorbidities, life expectancy, patient preference and more.
Achieving 15% weight loss cannot be done with lifestyle intervention alone. Data from multiple studies have shown bariatric surgery is associated with greater than 15% weight loss. Additionally, trial data have shown pharmacotherapies, such as semaglutide (Ozempic, Novo Nordisk) and tirzepatide (Mounjaro, Eli Lilly), have allowed some people with diabetes to achieve weight loss of 15% or greater.
Providers need to identify each patient’s type 2 diabetes subtype to figure out the treatment target to prioritize. For most, a weight-centric approach with a body weight loss of 15% or greater works best, Lingvay said. However, those with diabetes and CVD may benefit more from a cardio-centric approach with the use of proven cardioprotective agents, and those with isolated hyperglycemia may better benefit from a glucocentric approach with an HbA1c target of less than 7%.
Lingvay said there are potential drawbacks to weight loss, such as gallbladder disease, sarcopenia, bone loss, surgical complications, cost and adverse events from drugs, but the benefits of improved metabolic control, mechanics and quality of life almost always outweigh the negatives.
“The benefits are so overwhelming, unless you cannot manage the drawbacks, I see no reason not to do it,” Lingvay said. “Even in patients with type 1 diabetes, if they have adiposopathy, they will benefit from weight loss.”
HbA1c among several primary treatment targets
Mechanick said primary targets in type 2 diabetes should not be mutually exclusive. The best way to manage the disease is to take an approach that optimizes benefits for the individual patient.
“Glucose control is a necessary, but not sufficient primary target in patients with type 2 diabetes to prevent the development and progression of complications,” Mechanick said.
Pinpointing obesity as the singular primary target for type 2 diabetes care is flawed for several reasons, according to Mechanick. He noted obesity is defined strictly by BMI; adverse metabolic effects and beta-cell defects require comprehensive care; not all people with type 2 diabetes also have obesity; obesity and hyperglycemia are not mutually exclusive clinical targets for cardiometabolic prevention; and evidence has not stated the absolute superiority of weight control over glycemic control in type 2 diabetes.
Targeting hyperglycemia may be best for certain patients, including those with severe hyperglycemia, mild obesity or those at higher risk for hyperglycemia-related complications compared with obesity-related complications. A 3D cardiometabolic-based chronic disease prevention model first published in the Journal of the American College of Cardiology in 2020, showed hyperglycemia should be prioritized over obesity as a primary target in patients with stage 3 or 4 dysglycemia-based chronic disease, severe hyperglycemia, those with a lower stage of adiposity-based chronic disease and those with a higher stage of cardiometabolic-based chronic disease, Mechanick said.
“This is going to require thought on your part as health care professionals to not just accept that a high blood sugar means that’s how the patient will be classified,” Mechanick said. “Do a deeper dive into your patient to identify what are the different drivers and how are they prioritized.”
Controlling hyperglycemia is good in terms of reducing microvascular and CV complications of diabetes, according to Mechanick. The ADA Standards of Care includes a section of glycemic targets for people with diabetes, with a scale included to help providers determine a glycemic target based on an individual’s profile.
Mechanick agreed with Lingvay that weight control is the most important part of treating type 2 diabetes for most patients with the disease and should be the primary target for many. However, he added that focusing solely on weight control is not a pragmatic approach.
“Glucose control is also important, especially to mitigate the progression of dysglycemia-based chronic disease,” Mechanick said. “Both views represent valid interventions according to the cardiometabolic model. Both views are valid. Obesity and glycemic control are critical components of comprehensive care of patients with type 2 diabetes. It’s the timing and intensity of intervention, the individual scenarios and other factors that weigh in.”
Mechanick said future discussions on treatment targets for type 2 diabetes must be focused on codifying risks, attributing priorities based on relevant outcomes, and designing evidence-based strategies and tactics to optimize the outcomes within a comprehensive preventive care plan.
References:
- ADA Standards of Medical Care in Diabetes – 2022. Available at: https://diabetesjournals.org/care/issue/45/Supplement_1. Accessed June 5, 2022
- Mechanick JI, et al. J Am Coll Cardiol. 2020;doi:10.1016/j.jacc.2019.11.046.
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Lingvay I, et al. Weighing the Evidence — Should Obesity Be the Primary Target of Treatment in Type 2 Diabetes. Presented at: American Diabetes Association Scientific Sessions; June 3-7, 2022; New Orleans (hybrid meeting).
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