BOSTON — Early, aggressive management typically used to prevent complications of type 2 diabetes is also the best strategy to tackle prediabetes and its related comorbidities, according to a speaker at the American Association of Clinical Endocrinologists annual meeting.
Leigh Perreault, MD, associate professor of medicine at the University of Colorado Anschutz Medical Campus, said intensive lifestyle intervention and medical therapy before the development of overt type 2 diabetes is key to preventing long-term microvascular and macrovascular complications in people with prediabetes, who carry a strikingly similar risk burden.
“Prediabetes is diabetes,” Perreault told Endocrine Today. “The time is now to take action. You can prevent diabetes, you can prevent complications of diabetes, [the patient] can be a good role model for [his or her] family. It’s really an investment at that very moment in the patient’s future health. I find no other group of patients to be more motivated than people with prediabetes. It’s really an opportunity for clinicians to make a huge difference in their patients’ lives.”
During a presentation on goals for medical treatment in obesity and prediabetes, Perreault stressed that the burden of cardiovascular risk is the same in prediabetes and type 2 diabetes, largely because providers generally do not intervene aggressively enough in prediabetes.
Similar risks, complications
Findings from landmark studies like the Diabetes Prevention Program have led to an increasingly rigorous road map for how to treat people with diabetes, Perreault said. The American Diabetes Association’s annually updated Standards of Medical Care in Diabetes for 2018 is currently 121 pages.
“It has resulted in an incredible decline in the complications our patients [with type 2 diabetes] experience,” Perreault said. “What is far less elaborate in this 121-page document is how to take care of people with prediabetes. Prediabetes is considered a high-risk state — a ‘pre-disease’ and not really a disease by itself. So, the recommendations from ADA largely revolve around the prevention of diabetes.”
However, the complications of type 2 diabetes are already observed in many patients with prediabetes, Perreault said.
For example, research shows that although the incidence rate of myocardial infarction in patients with type 2 diabetes has declined, the prevalence of MI has increased because patients with type 2 diabetes are living longer, Perreault said.
“If you plot the prevalence rates of people with prediabetes, it is almost overlapping [with type 2 diabetes],” Perreault said. “Why? Because the rates of MI in people with prediabetes might be lower, but the collective burden of the number of people in the U.S. with prediabetes — 84 million — makes the prevalence the same.”
Use of off-label agents
Perreault noted that the AACE prediabetes algorithm calls for treating impaired glucose tolerance with lifestyle intervention, including medically assisted weight loss, and low-risk glucose-lowering medications, including metformin and acarbose. The algorithm recommends thiazolidinediones and GLP-1 receptor agonists be considered with caution in the treatment of prediabetes.
“None of these drugs have an FDA indication [for prediabetes], but AACE says, ‘We don’t want to just wait,’” Perreault said. “We need to do something now, before they get diabetes, before they suffer complications.”
The central goal, she said, is the restoration of normal glycemia.
Weight-loss therapies reduce the onset of diabetes just as well as glucose-lowering medications, Perreault said, and can similarly reduce CV complications.
Perreault cited a series of studies that suggest the power of both the placebo and conditioning effects in patients, noting that a response to a medical therapy can differ based on both a person’s expectations and previous experience with the agent.
That information, Perreault said, should be used to a provider’s advantage when it comes to obesity and prediabetes.
“Patients are conditioned to come to us when they are not well and want to get better. The second they walk in the door, that is a highly conditioned response to seek help from a doctor. We are already there. Their desire is so strong to lose weight ... and their expectation is that you’re going to help.
“Nothing has transformed my approach to my patients as much as learning the neuroscience behind how important how we do what we do is. I tell patients, ‘I can see that you are excited to lose weight, and I can’t wait to be a part of your success story.’ And the expectation is that I have a lot of patients doing really well on this medication, and I have high expectations for them,” Perreault said.
Equally ineffective, Perreault said, is what she called the “nocebo effect” — stressing the unpleasant side effects of a weight-loss drug or mentioning the difficulty of losing weight.
“I want to be really careful here —I am not saying we should treat patients with ‘placebos,’” Perreault said. “But, balanced information is key. If I’m prescribing liraglutide ... I might say that GI side effects were common in people that received this drug and in people that received the placebo, but, fewer than 10% of people left the trial because of adverse effects. That means 90% of people stayed in the trial because symptoms were not that bothersome. That is a completely true statement. But you deliver it that way, with the emphasis on the positive side.”
Perreault said it is important for providers to become more experienced with prescribing weight-loss medications so that they can help frame patient expectations in an optimistic way.
“How we deliver drug therapy to patients can absolutely, dramatically impact their success,” Perreault said. “The success I am having with weight-loss medications is way bigger than anything I have ever seen in clinical trials. So, try it. See if you can help your patients, too.” – by Regina Schaffer
Perreault L. Goals for Medical Treatment in Obesity and Prediabetes: Improving Outcomes. Presented at: AACE Annual Scientific and Clinical Congress; May 16-20, 2018; Boston.
Disclosure: Perreault reports she has received consulting or speaker fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Medscape, Merck/Pfizer, Novo Nordisk, Sanofi and WebMD.