Shifting the Paradigm: Targeting Weight Loss as a Primary Therapeutic Target in Type 2 Diabetes

Key Takeaways

• One of the prime ways we can improve clinical outcomes in type 2 diabetes is to help patients lose weight.
• Reducing weight decreases the risk for complications of excess weight and other comorbidities and the need for medications to treat them.
• Updated guidelines from the American Diabetes Association likely will place more emphasis on weight reduction as a primary treatment target of type 2 diabetes.

Having inadequate insulin secretion is the absolute cause of high blood sugar in diabetes. However, I think the management of excess weight in patients with diabetes is important, as excess weight contributes to the development of diabetes and is the explanation for why we have seen such a tremendous increase in the prevalence of diabetes over the past 20 years.

Managing the Supply and Demand for Insulin and Weight Loss
When I talk with patients about why they have diabetes and what we are trying to do to treat their diabetes, I like to use the analogy of supply and demand. If we can keep the demand for insulin below the maximum amount the patient can make, blood sugar will be within the normal range. The causes for increasing demand are excess weight, eating high‑carbohydrate foods, and not exercising. Therefore, one of the prime ways to decrease the demand for insulin is to help patients lose weight. Why would you not treat the major driver for high blood sugar and the development of hyperglycemia?

Why Weight Loss Should Be Considered as Treatment
We need to be aware that excess weight also contributes to the complications ascribed to diabetes, particularly cardiovascular disease, chronic kidney disease, and, to some extent, heart failure. With both excess weight and diabetes, the increased risk for these complications is exacerbated.

We also know that people who carry excess weight often have a significant number of comorbidities outside of their diabetes that puts them at risk for future complications, including hypertension, dyslipidemia, fatty liver, sleep apnea, reflux, arthritis, osteoarthritis, and certain cancers. In many cases, by treating the excess weight, some of these comorbidities can be eliminated and the need for medications to treat them minimized. If I can help someone lose 10% or 15% of their body weight, many comorbidities will resolve, and I can simplify their medications both for diabetes and for other weight related comorbidities. It becomes crystal clear that we have traditionally been treating all the complications of excess weight, but we are not dealing with a fundamental cause. A key reason for managing weight is to decrease the risk for complications of the weight and the need for medical and surgical treatments of the complications of excess weight.

Studies also have shown that with aggressive diet therapy, a 15% weight loss is associated with a remission of diabetes. This is especially true for patients early in their diabetes journey, as they can have a potential remission or at least a significant delay in the progression of their diabetes.

Another consideration is patient satisfaction. When patients are told that they need to lose weight because their excess weight is the reason they have diabetes, but then they are not successful in their weight loss, it can be very discouraging. We all know that it is incredibly difficult. The reason is not all willpower. There is a fundamental aspect of physiology that the body tends to defend its setpoint, by increasing appetite and lowering energy expenditure, both of which contribute to the difficulty losing weight, and if lost, maintaining that loss. As you know, it is uncommon for our patients to be able to lose the amount of weight needed to have an impact on comorbidities with just diet and exercise.

Pharmacologic Treatments for Weight Loss and Blood Sugar Control
The medications that are currently approved for weight loss, fundamentally change the set point at the level of the appetite control center in the brain. I find that when patients are given pharmacologic therapy to help them lose weight, they are more motivated to do the other things that we have been encouraging them to do to help with their weight and diabetes. Initial weight loss from medication can establish a positive cycle that leads to more interest in and comfort with exercise—and with more exercise, patients pay more attention to their diet. Therefore, it is really a good place to get started for those patients.

ADA Guidelines and the Weight Loss Pathway
The current American Diabetes Association (ADA) guidelines prioritize glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and sodium-glucose cotransporter 2 inhibitors for patients with comorbidities such as chronic kidney disease, heart failure, and atherosclerotic cardiovascular disease and include a separate pathway for considerations for patients who need to lose weight or have a compelling need to avoid hypoglycemia. Based on an early draft of proposed updated guidelines presented at the ADA meeting in June 2022, these recommendations likely will change to place more emphasis on the selection of agents that have demonstrated higher amounts of weight loss, such as certain GLP-1 RAs and tirzepatide, a glucose-dependent insulinotropic polypeptide/GLP-1 RA.

So, not only are the guidelines highlighting the use of GLP‑1 RAs and the importance of consideration of weight, they also tell us that this is something we should be prioritizing. Based on what I am seeing in the use of these agents in practice, I think healthcare professionals (HCPs) are finally understanding and starting to use these agents, not only because of their powerful A1C reduction, but also because of the weight reduction. HCPs have been waiting for something that was powerful enough to have an effect that both they and their patients find meaningful. Although a 5% weight loss is enough to change certain measures and complications, it is still deemed inadequate by most patients and HCPs.

This is an exciting time, so please check back in September for the presentation of the final update of the guidelines at the 2022 European Association for the Study of Diabetes conference!

Your Thoughts?
In your practice, are your patients with type 2 diabetes and obesity interested in pharmacotherapy for weight loss and blood sugar control? Answer the polling question and join the conversation in the comments section.