Experts debate best approach to type 2 diabetes in obesity
LAS VEGAS — When an individual has obesity with type 2 diabetes, the treating clinician should first focus on lowering blood glucose — not body weight — to reduce the end-organ complications that lower quality of life and increase mortality risk, according to a speaker at ObesityWeek.
Randomized controlled trials suggest that intensive lifestyle interventions and obesity medications can improve body weight and HbA1c for a person with type 2 diabetes and obesity, Jack Leahy, MD, professor of medicine in the division of endocrinology, diabetes and metabolism at the University of Vermont College of Medicine in Burlington, said during a debate on the optimal management of diabetes among patients with obesity. However, real-world studies demonstrate that those benefits do not always translate for the person in the clinic who is prescribed such therapies.
“The average patient with a chronic disease goes to their general practitioner, is seen for a moderate amount of time, and receives a prescription for one or multiple drugs,” Leahy said. “That works for the diabetes approach, but you can’t do things that way with an obesity medicine approach. It is person-intensive, time-intensive, and I don’t know how you fully translate that to the real world.”
The “primary goal” for the person with obesity and type 2 diabetes is to keep the person healthy and prevent diabetes end-organ complications, Leahy said — and diabetes medications, such as SGLT2 inhibitors and GLP-1 receptor agonists, will achieve those goals more efficiently than lifestyle modification or weight-loss drugs.
“To do that, we focus on optimizing HbA1c,” Leahy said. “For me, there is no debate. Fix the blood glucose, and then we will worry about weight.”
An ‘obese-centric’ approach
The diseases of type 2 diabetes and obesity are integrally linked, W. Timothy Garvey, MD, FACE, professor of medicine and chair of the department of nutrition sciences at the University of Alabama at Birmingham, said during his portion of the debate.
A focus on diabetes, Garvey said, will address hyperglycemia but not treat the obesity, and will not optimally prevent or ameliorate the impact of obesity on health, quality of life, biomechanical complications, and cardiometabolic disease. However, weight loss therapy will treat the whole patient with obesity as well as improve glycemic with less need for conventional diabetes medications.
“What if there was a magic pill for diabetes that reduced HbA1c by 0.5% to 1.6% and at the same time reduced diabetes medications, led to a 5% to 15% reduction in body weight, reduced blood pressure, reduced triglycerides and raised HDL cholesterol, got fat out of the liver, was renoprotective, improved sleep apnea, improved mobility, decreased pain and improved quality of life?” Garvey said. “There is no diabetes medication that is going to give you this therapeutic profile, and this is the therapeutic profile of weight loss in type 2 diabetes.”
Weight-loss therapy, Garvey said, is defined as expert care using all of the tools available to obesity medicine physicians and health care professionals. This includes lifestyle interventions, medications and bariatric surgery. As an example, data from the Diabetes Remission Clinical Trial (DIRECT), which assessed whether intensive weight management within routine primary care would achieve remission of type 2 diabetes, demonstrated that diabetes remission was achieved among 46% of participants in the intervention group and 4% of participants in the control group, Garvey said. Diabetes remission was even greater among participants who lost 15% body weight.
“There is no diabetes drug that will do that,” Garvey said.
Similarly, weight-loss medications, such as phentermine/topiramate extended-release (Qsymia, Vivus), lorcaserin (Belviq, Eisai), naltrexone/bupropion ER (Contrave, Nalpropion Pharmaceuticals) and liraglutide 3 mg (Saxenda, Novo Nordisk) are associated with improved glycemic response and less need for diabetes medications, Garvey said. Bariatric procedures, such as Roux-en-Y gastric bypass, are also associated with diabetes remission and reduced cardiometabolic complications.
Diabetes drug benefits
However, diabetes medications, in particular SGLT2 inhibitors and GLP-1 receptor agonists, are also associated with significant weight loss, are easy to take in oral form with the newly approved oral SGLT2 inhibitor semaglutide, have minimal adverse effects and present low risk for hypoglycemia, according to Leahy. With SGLT2 inhibitors, a person with high CV risk along with obesity and diabetes can derive a cardioprotective benefit after just 6 weeks, he said.
In the landmark Look AHEAD study, a long-term, intensive lifestyle intervention targeting weight loss among more than 5,100 adults with type 2 diabetes and overweight or obesity, weight loss was modest and participants did not experience a reduction in CV events, including nonfatal myocardial infarction and nonfatal stroke, Leahy said.
“Which would be better: to spend a number of years working hard on lifestyle modification or to take a daily SGLT-2 inhibitor that would give you benefits within 6 weeks?” Leahy said. “What would result in better quality of life?”
Still, Leahy said, in the real world, clinicians focus on HbA1c and body weight.
“The message from me is not ignore weight — not at all,” Leahy said. “But you made me choose, and if you’re going to fix anything, you have to work on the HbA1c. Plus, it is not guaranteed that everyone who undergoes the obesity medicine approach attains a 10% weight reduction, which is a key goal for metabolic benefits.”
Garvey said it is important to remember that obesity is a driver of type 2 diabetes.
“By treating obesity confidently, we can address issues that are complications for obesity and diabetes, which can be considered a complication of obesity as well,” Garvey said. “If you want to practice evidence-based care, do not forget obesity medicine to help patients with obesity and diabetes get serious about weight-loss therapy.” – by Regina Schaffer
Garvey WT, et al. Debate: Management of type 2 diabetes — glucose vs. obesity-centered approach. Presented at: ObesityWeek 2019; Nov. 3-7, 2019; Las Vegas.
Disclosures: Garvey reports he has served on advisory boards for Alexion, Eisai, Merck, Novo Nordisk, Takeda and Vivus, and received research support from AstraZeneca, Elcelyx, Lexicon, Merck, Novo Nordisk, Pfizer and Weight Watchers. Leahy reports he has served as an advisory board member for Merck and Novo Nordisk.