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Comprehensive Care for Obesity
Integrating Weight Loss Medications, Lifestyle Changes, and Comprehensive Care for Optimal Obesity Management

Released: December 10, 2024

Expiration: December 09, 2025

Jaime Almandoz
Jaime Almandoz, MD, MBA, MRCPI, FTOS
Domenica M. Rubino
Domenica M. Rubino, MD
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Key Takeaways
  • When using medications for treating obesity, it is essential to incorporate diet and lifestyle changes alongside medication to optimize outcomes.
  • The primary goal of using medications like GLP-1 RAs is not to achieve the maximum weight loss but to improve overall health, manage comorbidities, and enhance quality of life.

In this commentary, experts address important clinical questions regarding the use of obesity medications, titration, and nutrition in patients with obesity or type 2 diabetes (T2D).

If patients with diabetes do not respond well to nutrient-stimulated hormones, then why are the doses lower in diabetes?

Domenica M. Rubino, MD:
The reason for this is that most of the T2D studies were completed first before the obesity studies. Initial dosing for nutrient-stimulated hormones might be lower from an approval standpoint. When treating a patient, the decision often comes down to whether I am managing T2D or obesity, which is heavily influenced by insurance. Unfortunately, it is often easier if patients have diabetes for them to qualify for treatment, as managing obesity is currently much more challenging. For tirzepatide, the dosing for both T2D and obesity is the same, and for semaglutide, the 2.0-mg dose for T2D and 2.4-mg dose for obesity do not provide significant differences in benefit. Mostly the dose and titration depend more on the patient’s response and tolerability. Initially, development programs focused on T2D first, then obesity. However, moving forward, you will see both being addressed simultaneously, as there is a growing recognition of the need to treat all related comorbid conditions.

What are your thoughts on up-titrating medications to the maximum dose monthly, and how do you approach this clinically when a patient comes in, including how often you see them for follow-up? 

Domenica M. Rubino, MD:
I see my patients every month when I am titrating their medication. If patients are responding well, meaning they are managing their diet and lifestyle interventions, feeling better, and starting to lose weight, I keep them on the lowest dose that supports that progress. Many clinical trial protocols often require dose escalation to assess the effects at each level, aiming to reach the target dose. However, in the evolution of these studies, many phase III trials now allow patients to stay at a lower dose, if the higher dose is not tolerated. Personally, when treating my patients, I prefer using the lowest effective dose because I believe the adverse effects that come with higher doses are unnecessary. I find that combining exercise, diet, lifestyle changes, proper nutrition, and the use of medications that target physiology and the patient’s perceived cognitive approach to food management works well to help patients achieve their goals. There is no rush to reach a specific dose; in fact, many of us in this field believe that slower weight loss, accompanied by behavioral changes, leads to better long-term outcomes.  

Jaime Almandoz, MD, MBA, MRCPI, FTOS:
You raise an important point about how rapid or forced titration can lead to gastrointestinal adverse effects, like nausea, which can contribute to malnutrition and loss of lean mass. This also affects patients’ willingness to engage in physical activity or resistance training, which is crucial for preserving lean muscle mass. It is not simply a matter of treating nausea with medication and moving to the next dose. 

Domenica M. Rubino, MD:
As an obesity medicine physician, I need to ascertain if patients have nausea but can still eat or if they are not eating at all. Many times, I must extract this information from patients because they want to stay on this medication no matter the circumstances because they are losing weight. I must think about the total health of the patient suffering from obesity and help the patient realize that it is not a weight loss race. An important aspect to remember when prescribing these obesity medications is you should ensure your patient’s proper nutrition.  Sometimes, I have to do some investigation to truly understand what my patients are consuming, as they may not always be forthcoming. Since they often are willing to try anything to lose weight, they might not disclose everything.

Jaime Almandoz, MD, MBA, MRCPI, FTOS:
A game changer for these patients is not having to approach eating with a constant restrictive mindset, but instead focusing on what their body needs to function in a healthy state.

How do you dose glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) when the BMI is <27? Do you reduce the dose or space out the administration, and should you be targeting a specific BMI? 

Domenica M. Rubino, MD:
I do not set a BMI target but instead see where each patient will level out or reaches a fat mass set-point. I do not go for 100% hunger suppression. I am concerned that complete suppression of hunger may lead to greater weight rebound in patients, but minimal suppression makes it difficult to make lifestyle changes. In my clinical experience, patients can maintain weight loss on one half of their regular dose or even lower, especially if active. Currently, there is not a lot of information about what to do in the maintenance phase. However, there are studies to show that weight resistance training and high protein intake help to preserve muscle during the weight loss and maintenance phase. During the maintenance phase, until more data come out, I focus on meeting the patients where they are.

With increasing access to weight loss medications for older adults with cardiovascular disease, is there a point where you start to be concerned about their weight loss? For example, if a 72-year-old patient with a high starting BMI and a history of coronary bypass surgery reaches a low BMI, how do you approach that conversation? 

Domenica M. Rubino, MD:
Overall, I must take care of my patients from a health perspective. I have to ask myself if it is sensible for an older patient to keep losing weight or if there is a point where it becomes dangerous. For older patients, before losing any more weight, I make sure they are working with a physical therapist to decrease muscle loss. I make sure they are getting stronger and fueling themselves properly. If they are doing all these things, then I will revisit more weight loss, but usually at a lower dose than before.

Jaime Almandoz, MD, MBA, MRCPI, FTOS:
Unfortunately, there is a lot of weight loss bias and stigma that impacts the way we treat obesity that is not seen with other diseases. By viewing obesity as a chronic and complex disease, acknowledging the variability in response, both in terms of weight change and from a cardiovascular, kidney, and metabolic perspective, as well as adverse effect profiles, there has to be individualized treatment. This approach allows healthcare professionals to collaborate with patients to achieve the best possible outcomes. 

Are GLP-1 RA nonresponders more or less likely to be responsive to bariatric surgery? Do you consider a lack of response to medical therapy as an indicator that a patient may not respond to surgery? 

Jaime Almandoz, MD, MBA, MRCPI, FTOS:
What continues to surprise and humble me over the years is when a treatment does not work for a patient, and then you try something else that you doubted would work, and it leads to a dramatic response. This is just a reminder to not write patients off if they do not respond to one treatment. Make sure to continue to offer patients what you believe to be the best, safest, and most effective treatment. Also, continue to educate yourself on how new treatments differ in their mechanisms of action. The goal should not just be to achieve the greatest weight loss in the hope that health benefits will follow but to select targeted therapies that improve both the health and quality of life of patients.

Is there a concern for increased heart rate with glucagon agonists and GLP-1 RAs?

Domenica M. Rubino, MD:
Glucagon is a chronotropic agent. GLP-1 RAs also have chronotropic and ionotropic effects on the heart. We do see on average 3-5 beats per minute increase in heart rate with GLP-1 RAs. The data from the SELECT trial show that the use of semaglutide is associated with a 20% risk reduction. Survodutide has a cardiovascular outcome trial that is ongoing, so we will know more about that in future. Retatrutide has shown some increase in heart rate that appears to be dose related. I think the phase III and cardiovascular trials are going to help us understand better what the clinical impact of these agents will be on the heart.  

Your Thoughts?
How frequently do you discuss diet, exercise, and lifestyle changes with your patients in addition to their obesity medications to ensure the best possible outcomes? Get involved in the discussion by answering the polling questions and posting a comment below.

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