Jennifer B. Green, MD

The Future of Incretin Therapy with Jennifer Green, MD

 sat down with Jennifer Green, MD, professor of medicine at the Duke University School of Medicine, to discuss her presentation on the past and future of incretin-based therapy in 

Incretin therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists have long been used in treating obesity and diabetes. However, many modern incretin-based medications have been adapted to a variety of comorbidities, including 

Green suggested that these treatments may even be effective in treating Alzheimer’s and Parkinson’s, among other neurodegenerative diseases.

“When we think about the CNS effects of the incretin-based therapies, the GLP-1 based therapies, we tend to think most about the way that these agents can suppress appetite, but their effects may be much more broad than that,” Green told 

. “So it is thought, for example, that our body’s own GLP-1 can reduce inflammation in the brain, and in fact might stimulate neurogenesis.”

Green also expressed interest in the recently conducted SURMOUNT-OSA trial examining tirzepatide’s efficacy in treating sleep apnea.

“SURMOUNT-OSA showed that, in individuals randomized to active tirzepatide therapy, at the end of the study almost half of them didn’t even have sleep apnea anymore, which is really incredible: you’re fundamentally addressing and perhaps eliminating an entire disease state,” Green said. “And within the spectrum of metabolic diseases, I would say that’s exceptionally rare.”

Although trials are ongoing to investigate the efficacy of incretin-based therapies in treating other diseases, Green acknowledged the potential roadblocks to such studies, indicating that they are still in early stages.

“For example, if a person is enrolled in a trial of a weight loss medication that they know has the potential to result in very dramatic weight loss, but they’re randomized to a placebo, it might be easy for the participants to become unblinded,” Green said. “If half of the patients are losing a tremendous amount of body weight and the other half are not, we might inadvertently or unintentionally break the blind of a trial, which is a major trial conduct issue.”

Green explained that managing patient expectations is a major challenge in testing incretin-based therapies across the board. Each patient enrolled in these trials is hoping to receive the active drug; if they discover that they have been given placebo, Green believes there is a danger that they will drop out of the trials. Green suggested an alternative method of comparing newly developed incretin-based therapies to existing medications in the form of active controls to avoid this clinical disruption.

Given the speed at which investigations into incretin-based therapies are being adopted, Green stresses the importance of remaining informed and adapting clinical practices to include newly discovered treatments and processes.

“I think it’s important to stay abreast of the literature, because there’s just more and more information becoming available every month that we need to understand and incorporate into our clinical practice,” Green told 

Green reports the following disclosures: Boehringer Ingelheim, Lilly, Merck, NovoNordisk, AstraZeneca, Merck, and others

Green J. Incretins: Today and Tomorrow. Presented at the 9

 Annual Heart in Diabetes Conference in Philadelphia, PA, June 6-8, 2025.

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Incretin-based therapies for obesity and diabetes may be capable of treating a much wider range of diseases, including Alzheimer’s and Parkinson’s.

Jennifer B. Green, MD: Implementation of Evidence-Based Therapies for T2D

22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC)

, Jennifer B. Green, MD, an endocrinologist and a clinical trialist at Duke University Medical Center, provided updated insight into the implementation of evidence-based therapies for high-risk patients with 

Green highlighted the success of the COORDINATE-Diabetes trial, which aimed to improve the adoption of essential therapies—high-intensity statins, ACE/ARB inhibitors, and sodium-glucose co-transporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists—in cardiology clinics for patients with T2D and established atherosclerotic cardiovascular disease (ASCVD). The trial showed significant improvements in treatment adherence, addressing a critical gap where only 3-4% of patients were initially receiving all recommended therapies. Green also emphasized the importance of continuing medical education, noting that conferences like these help clinicians stay updated on evolving management strategies, particularly for managing cardio-renal complications in diabetes.

Reflecting on advancements in 2024, Green pointed to the expanding benefits of therapies like GLP-1 receptor agonists and SGLT2 inhibitors, which, beyond managing glucose and weight, are now shown to provide substantial cardiovascular and kidney-related outcomes. She expressed satisfaction in knowing that her prescribing practices are delivering broader benefits than initially expected, reinforcing the importance of implementing the latest evidence to improve patient outcomes.

Disclosures: Relevant disclosures for Green include Bayer, Boehringer Ingelheim, Eli Lilly, Merck, and others.

Green JB. From Research to Guidelines to Implementing Good Clinical Practice in the Management of Diabetes. Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.

Dr. Jennifer B. Green discussed the implementation of evidence-based therapies for high-risk type 2 diabetes patients at the WCIRDC. She highlighted the COORDINATE-Diabetes trial's success in improving adherence to essential therapies in cardiology clinics, addressing a significant treatment gap. Green emphasized the role of continuing medical education in updating clinicians on management strategies, particularly for cardio-renal complications. She noted the expanding benefits of GLP-1 receptor agonists and SGLT2 inhibitors, which now show substantial cardiovascular and kidney-related outcomes, underscoring the importance of applying the latest evidence in practice.

Jennifer B. Green, MD highlights the successful implementation of evidence-based therapies for high-risk patients with type 2 diabetes.

 We can’t forget about insulin therapy. Insulin is a very effective tool. I talk about insulin as though it’s 1 thing, but there are many types of insulin being developed. One area that has seen a tremendous amount of evolution in recent years is the development of artificial pancreas systems. We have devices available that include both an insulin delivery component and a glucose sensor, or CGM [continuous glucose monitoring], component that are at least partially linked. The insulin delivery in at least some respect is directly affected by the ambient glucose level that the sensor detects.

We have a couple of devices that alter basal insulin delivery based on what the glucose level is, and that represents an exciting step forward. A true artificial pancreas—there are many such systems in development—would be completely hands-free or at least come very close. There are also a number of systems in development that include an algorithm or very sophisticated algorithms that alter insulin adjustment—not just for basal insulin delivery but for correction insulin or, to some extent, mealtime insulin in response to the individual’s activity and blood glucose level that will come a little closer. None of those hands-free systems are in development, but they’re getting closer.

We’ve seen published data, particularly in the pediatrics population, that look incredibly promising. Consistently, almost all the trials I’ve reviewed suggest that these kinds of systems reduce the risk of hypoglycemia compared with the traditionally available semi-integrated systems. The challenges we’ll see moving forward will be how these systems can be designed to account for meal intake, how to customize or appropriately deliver insulin in response to what the person is eating, and how the system reacts to hypoglycemia, should it occur.

Some of these systems are dual-hormonal systems that infuse not just insulin but also glucagon. Although none of these appear extremely close to becoming available, within the next 5 years, we’ll probably have multiple systems on the market that I hope will make life much easier for individuals who require these sophisticated insulin delivery systems. They’re not just for people with type 1 diabetes. These systems hold great potential for people with type 2 diabetes who need this intensive and complex treatment as well.

 Technology has certainly taken off. We have penny-size sensors for continuous glucose monitoring. We have subcutaneously implanted sensors. We get a lot of questions from patients who might not necessarily benefit from sensors. They may be cardiovascular patients or any patient with diabetes who says, “I’m on 2 medications. I’m on metformin, and my hemoglobin A1C [glycated hemoglobin] is 6.8%. Should I wear a sensor?” That’s probably not helpful. These are meant more for patients on complex insulin regimens or multiple daily injections, combined with insulin pumps and an algorithm used to semiautomate—at least for now—the basal rates.

If you look at the requirements from the FDA for diabetes medications, they’re very stringent on outcome trials. For durable medical equipment, we’ve never had an outcome trial, other than looking at time in euglycemia or hemoglobin A1C. We don’t know well whether using a pump vs multiple daily injections would reduce microvascular or macrovascular complications. I alway s thought that would be a very interesting area to explore. But much of this has to do with quality of life in addition to quality of care. More time spent in euglycemia, safer insulin use, shut-off algorithms—basal insulin in the middle of the night—etc. These are the main advantages of pumps and continuous glucose monitoring. It’s available with phone data, so it becomes much more user friendly. If you look at pictures of how the first pump, the backpack pump, was developed to now automated algorithms, it’s really taken off. Diabetes care will become much easier, much safer, and outcomes will become much better in the future.

Some of the most encouraging data for us endocrinologists and cardiologists have been from a large Swedish cohort that looked at mortality data in patients with diabetes, emphasizing the comprehensive care model. I keep citing the Steno-2 trial in every presentation because it sends the message of comprehensive care, where if patients are treated with their hemoglobin A1C and albuminuria protected, and smoking, LDL cholesterol, and blood pressure all under control—all 5 of those factors were under control in this large Swedish cohort—there was no significant excess mortality across every age group. This is really encouraging. We have all the tools available to do that. The challenge will be to bring this to the wider population and to fill a lot of the gaps that we’re dealing with.

 I completely agree. I briefly mentioned the GRADE study. We have just a few moments left, but some of the information that trial will ultimately provide will be a bit of insight into personal phenotypes and drug choices that may be particularly effective and tolerable for individual patients. I’m interested to hear more from that study about personal phenotypes, individual predictors of accomplishment of good glycemic control, and even benefits from a microvascular or macrovascular perspective within the various classes of drugs that were studied in that trial.

Thank you, Dr Bruemmer. I’d like to thank everyone for watching this 

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Expert clinicians discuss insulin therapy for treating type 2 diabetes and comment on what to look forward to in the future of diabetes care.

Insulin Therapy and the Future of Type 2 Diabetes Care

 We should shift to what we see in the future as options to treat and improve the lives of patients with type 2 diabetes. One of the exciting topics at the last ADA [American Diabetes Association] meeting was related to data presented from the tirzepatide trial, which is a novel but not available combination GIP and GLP1 receptor agonist. This has been an interesting concept. There have been a number of agents in development that have had varying effects on GLP1 receptors, GIP receptors, and glucagon receptors, because we know that various degrees of stimulation or inhibition of those receptors can be associated with a wide and complementary way of metabolic benefits.

This agent, tirzepatide, appears to be closest to becoming available for treatment for our patients. The trial data were very exciting to see that use of this combination agent provided outcomes benefits, particularly with respect to weight loss and glycemic control, that appeared to reproduce and exceed those provided by the comparator GLP1 receptor agonist. We’re seeing an option for patients who either need more than effective and available GLP1 receptor agonism, or patients who might already be maxed out on the dose of a GLP1 receptor agonist that they can tolerate, or that’s FDA approved for glycemic control. Perhaps this represents a next step for such patients. We all have patients who are on as many classes as we feel are effective choices for them, but still struggle with glycemic control, weight management, or both. It’s very exciting to have at least 1 such agent on the near horizon. Did you have any other thoughts about the data that were presented?

 It’s fair to say that the data were quite powerful if not stunning. If you look at the SURPASS-3 trial data, the hemoglobin A1C [glycated hemoglobin] drop was 2.3% with 1 injection per week compared with degludec. More than 80% of patients achieved hemoglobin A1C of less than 7% in that study. That’s the most powerful drug that will become available. The maximum body-weight reduction was 12.9 kg compared with degludec, which raised the weight by 2 kg. It’s a very powerful medication, with less hypoglycemia, not just because of the comparison with basal insulin but also through the increased glucagon secretion that occurs with the GIP component of the dual incretin molecules. It’s a promising and powerful drug that will expand our tools that we have available.

One of the main challenges that we’re faced with is: how do we apply all these new medications to the broad population? How do we make this available? You mentioned that we need to be proactive in our care. That will be the main challenge: going from socioeconomics to formulary restrictions to access to patients to physicians and nurses. There’s a lot to be discussed and to be done, but it’s certainly a powerful medication.

 What we may see over time is a shake-up in the traditional stepwise approach to diabetes care, where you add 1 drug and essentially wait for it to fail before another is added. Perhaps we’ll be able to treat diabetes a little differently if we can choose very effective agents from the outset. Certainly, the GRADE trial results weren’t encouraging regarding long-term effectiveness of available agents, but we can talk about that further. That trial probably has much more interesting information to come.

Drs Dennis Bruemmer and Jennifer Green review recent trial data on a novel combination of GIP and GLP1 receptor agonists to treat type 2 diabetes.

Jennifer B. Green, MD

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