Research shows that even newer, more effective GLP-1 medications require long-term use to achieve weight loss benefits.
Although science indicates that obesity is a chronic disease, people are still looking for a short-term cure.
What GLP-1 drugs, bariatric surgery, diet and exercise have in common is that they require long-term treatment, according to an article by Dr. Thomas Rutledge, a resident professor in the Department of Psychiatry at the University of California, San Diego, published by Psychology Today.
Reversing the obesity epidemic will require effective initial treatments and long-term maintenance plans, the doctor said.
Research is important to us for many reasons. Sometimes, for example, research leads to a new treatment (such as Alexander Fleming and penicillin), or a new idea (such as Einstein’s theory of relativity), or a new way of working (such as Dr. Doudna’s CRISPR methodology for gene editing). Novelty is a key feature behind the importance of research.
However, sometimes research is important not because it offers us something new, but because it reminds us of something old that we were reluctant to accept. Research conducted last week on weight regain after stopping use of tirzepatide (Zebound) is an example of this.
Zepbound is an effective GLP-1 (glucagon-like peptide 1) medication that helps many people achieve significant weight loss and associated metabolic health improvements (such as diabetes, fatty liver disease, and sleep apnea).
The phase 3 clinical trial of Zepbound showed an average weight loss of more than 22 kilograms over a year of treatment. This level of weight loss remains unprecedented for any treatment except bariatric surgery. But this latest study asked a different question: What happens when people stop using the treatment?
The answer appears to be the same as for all other weight loss methods studied so far.
83% of them regained significant amounts of weight (more than 25% of the weight lost from treatment).
Among those who regained weight, participants also saw a decline in health indicators such as waist circumference, blood pressure and cholesterol, all of which rose.
For many people, trends in weight gain and poor health began almost immediately after they stopped treatment.
For decades, every new diet, exercise program, obesity surgery, and weight-loss drug seemed to raise in us the hope that permanent weight loss could be achieved with short-term treatment.
Each time, the harsh reality of weight regain dashed those hopes, only to have them miraculously return in time for the next popular treatment. In several long-term trials, weight-loss medications containing GLP-1 show the same pattern of weight regain when treatment is discontinued.
Why is weight regain (mostly) inevitable without long-term treatment?
Although weight regain poses a risk with every weight-loss treatment, results from the National Weight Loss Registry reveal that it is possible for some people to maintain significant weight loss. For example, people who both lose weight and maintain it off tend to:
- Eat regular meals and constantly monitor portion sizes, without following any specific diet
- Keep exercise a regular part of their lifestyle
- Measure their weight regularly
- Reduce inactivity, such as watching TV and using social media
The bottom line when it comes to long-term weight loss is that permanent weight loss requires permanent treatment.
Although diet and exercise programs, bariatric surgery, and GLP-1 medications lead to weight loss through various biopsychosocial mechanisms, their need for treatment (which may include, for example, sustained lifestyle changes, continued use of medications, or diligent adherence to nutrition after bariatric surgery) does not change.
For most people, maintaining weight loss requires a lifelong struggle with their own biology. This disturbing fact underlies the necessity of ongoing treatment.
Fat cells, for example, are not just passive energy storage vessels as is commonly thought. They are actually miniature organs in themselves, secreting specific hormones such as leptin to the brain during periods of weight loss, which increases appetite and reduces feelings of fullness.
Remarkably, fat cells retain memories of their state before weight loss in the form of epigenetic gene expression patterns. These genetic memories can force us to regain weight long after the loss has ended.
If these fat cell effects are coupled with equally powerful changes in the brain’s reward system pathways, which occur during periods of overweight and obesity, even the most intent person may find that their conscious weight loss goals have been overtaken by primitive human biology optimized over millions of years of evolution to prioritize weight regain over weight loss.
Overweight and obesity as chronic diseases
Following GLP-1 therapy points to a conclusion we already accept in many other aspects of our lives. What happens to fitness when you stop exercising? We maintain our daily routine of brushing and flossing our teeth because we know that tooth decay begins to appear once we stop these habits.
Most of us don’t need a phase III clinical study to realize this: everything we consider good must be defended. Maybe we can finally add weight loss to this list.
It is only recently that science and health care have recognized that excess body fat (i.e., overweight and obesity) is a chronic disease that requires long-term treatment and management.
If this seems self-evident, remember that it took until 2013 for the American Medical Association to officially recognize obesity as a chronic condition. Since its founding in 1847, experts from the world’s oldest medical society have viewed overweight and obesity as acute illnesses and accidents that can be treated with short-term interventions, but it has taken this long for the obesity trend to reverse.
The next critical step is to communicate this updated understanding to the general public. As long as we continue to view weight loss as a short-term problem, we will lean toward short-term solutions and suffer the physical and psychological burden of short-term results.
In contrast, once we collectively embrace healthy weight loss as a lifelong journey, long-term treatments that support weight loss and maintenance will become the new standard of care. This change has to start somewhere, so why not us?