Endocrinology Breakthroughs and Gaps in 2024
Irl B. Hirsch, MD, MACP, discusses his session, “Endocrine Year in Review,” presented at the 2024 American College of Physicians Internal Medicine Meeting. Dr Hirsch highlights key endocrine studies from the past year, including advances in GLP-1 receptor agonists, testosterone therapy, and continuous glucose monitoring. He also addresses the growing shortage of endocrinologists, its impact on primary care, and emerging developments in diabetes prevention, treatment, and rare endocrine conditions.
Additional Resource: https://annualmeeting.acponline.org/educational-program/scientific-program/scientific-sessions
Irl B. Hirsch, MD, MACP: My name is Irl Hirsch. I'm a professor of medicine at the University of Washington in Seattle. I've been here for 35 years, and I will be presenting the Endocrine Year in Review for the year 2024.
Consultant360: What are the key themes of your presentation?
Dr Hirsch: What I did was review what I consider to be the most important articles in endocrinology from January to December of 2024. I scanned The New England Journal of Medicine, The Annals of Internal Medicine, the JAMA series, the Lancet series, and Diabetes Care. I attempted to pick articles which I thought were the most relevant to the general internist. The problem, of course, is that certain articles may not be critical to everyone, and there's always the case for potential bias in a relatively short presentation of the entire field of endocrinology.
C360: Why is this topic particularly relevant right now?
Dr Hirsch: I really appreciate that question, because how I'm going to start my presentation is with the fact that the outlook for endocrinology access is not good. This means that the general internist is going to be more responsible for general endocrinology and, for that matter, diabetes. Nearly 70% of U.S. counties lack an endocrinologist, and we now call these endocrinologist deserts. These are data that came out in December of 2024. Currently, there are 50 million Americans that do not have access to an endocrinologist. And we know that in these endocrinologist deserts, 12% more people are likely to die from endocrine-related conditions. These are populations with higher risks of diabetes, obesity, and stroke. The gaps in endocrinology care span both rural and urban communities. There are many reasons for this. People are not going into endocrinology like they used to. This is going to create greater pressure on the general internist to be up to date with both general endocrinology and diabetes.
C360: What are the most important takeaways for clinicians in practice?
Dr Hirsch: What I'm going to focus on are some new drugs that are being tested for hot flashes in women; LP(a), lipoprotein(a), which is an independent risk factor for cardiovascular mortality. It is a lipoprotein which is genetically inherited. It's one of those things that we use to decide whether or not to start a statin. But a drug is being developed to see if it can lower cardiovascular risk by itself.
Maybe the more important parts of the discussion will be specifically about diabetes and obesity. That being said, in the last year we also learned about testosterone replacement and fractures in men with hypogonadism. For example, there was a study presented the year before last called the TRAVERSE Study, which did not show any impact on cardiovascular risk with testosterone replacement in hypogonadal men. But the study I will be describing talks about testosterone replacement and fractures. The thought was that with gonadosteroid deficiency—estrogen in women and testosterone in men—if you replace, in this case, testosterone in men, you would see an improvement in fracture risk. In fact, the opposite was seen. That was a complete surprise. We don't know for sure why that happened, but the thought is that since the fracture risk went up right away, maybe this had to do with the behavior of the men. The men felt they were able to do more exercise; they were more anxious to get out and be active. Maybe that had to do with the increased risk of fracture. We don't know, but we will go into that in some detail.
I am also going to look at a meta-analysis of cardiovascular mortality with testosterone replacement. The bottom line is, there is no impact of testosterone replacement therapy on cardiovascular disease. I'm going to review a new scoring system—staging system—for pituitary tumors. And I'm also going to look at the impact of GLP-1 receptor agonists in conversion of prediabetes to diabetes. As it turns out, with one particular GLP-1 receptor agonist—which is also a GIP agonist—there was a 93% reduction in developing type 2 diabetes from people with prediabetes. A 3% risk reduction, which is really incredible.
In my practice, maybe one of the most important studies of the year was the FLOW trial. This was the trial looking at renal outcomes in patients with type 2 diabetes. The treatment was semaglutide versus placebo, and what was shown was a reduction in major kidney disease events and a reduction in death from cardiovascular disease. In January 2025, semaglutide received a label from the FDA to reduce the risk of worsening kidney failure and death from cardiovascular events in patients with type 2 diabetes and chronic kidney disease. There is so much kidney disease in type 2 diabetes, and now this is the first GLP-1 receptor agonist that actually has the label for this. This had been shown in secondary analyses until now, but this is the first primary endpoint using kidney disease with a GLP-1, so this is also very important.
The other part I want to emphasize is that there has been incredible concern about cancer in general, and in particular thyroid cancer, with the use of GLP-1 receptor agonists. This stems from animal studies showing a concern of medullary carcinoma with GLP-1 receptor agonists. I will be showing data to show that that is not the case. In fact, as a rule of thumb, if anything, we see a reduction in all cancer and cancer mortality. The reason for this is most likely related to weight loss, because we know that obesity is an independent risk factor for malignancy. There are probably many reasons for this, with hyperinsulinemia and growth factors. But importantly, as far as thyroid cancer is concerned, there was absolutely no increase in any subtype of thyroid cancer with these GLP-1s. I think clinicians can be much more confident that this is not an independent risk, and that they can safely use these agents without worrying about thyroid cancer.
Endocrinology is so big. I don't think most American physicians appreciate that in Europe and other places around the world, endocrinology and diabetes are separate subspecialties. But here in the United States, it's one. There's a lot. In my talk, I will not be addressing anything related to pregnancy or pediatric endocrinology. That’s a lot of information, but I hope it’s helpful.
C360: What gaps in knowledge or areas for future research still remain?
Dr Hirsch: There are a lot of things we don’t know about, and we’re learning. I’ll be talking a little bit about the use of technology in diabetes. No surprise—in type 1 diabetes, the more technology that was used, the fewer complications we saw, specifically focusing on diabetic retinopathy. There’s another study I’m going to show that looked at continuous glucose monitoring in type 2 diabetes. I was actually one of the authors. We looked specifically at people who were either on no insulin therapy, basal insulin therapy, or basal-bolus (prandial) insulin therapy. We had over 36,000 people from an electronic medical record chart review.
What we showed is that with people on no insulin therapy, over a year of using continuous glucose monitoring, there was over a 10% reduction in all-cause hospitalizations. In general, continuous glucose monitoring is not even covered by insurance in this group. In people with basal insulin therapy, we saw almost a 14% reduction in hospitalizations. In those on prandial insulin therapy, it was a 22.6% reduction. To me, the most interesting part was that people on no insulin therapy, after a year of continuous glucose monitoring—again, we don’t know which brand—they had an A1C reduction from 8.6% to 7.5%. That’s a 1.1% drop.
We often think of this as a technology, but I prefer to think of it like adding another pharmaceutical agent. We consistently see these 1% or more A1C reductions with this technology. This has been seen in other studies too. Obviously, the device isn’t doing anything to insulin resistance or insulin secretion directly. This is all related to behavioral changes by the patient. They see that they eat something and their glucose spikes, or they do a certain type of exercise and their blood sugars improve. This is all about patient lifestyle.
Other studies, just recently published, show that this technology isn’t just cost-effective—it’s literally cost-saving over time. Another major area that’s becoming exciting is that we are really on the precipice of two different topics in type 1 diabetes: preventing type 1 and curing type 1. We now have a drug—teplizumab—that, when used just before type 1 diabetes becomes clinically relevant (stage 3), delays the need for insulin for two years. There are other drugs being developed that could potentially be used in combination with teplizumab. We’re also getting ready for stem cell transplants in type 1 diabetes that will eliminate the need for insulin. Those studies are ongoing right now, and I hope in future years we can talk more about them.
I’ve focused mostly on diabetes and obesity, but I want to emphasize that there are many advances in diagnosing and treating rare endocrine tumors. I think in the next few years, there will be much more to say about that. But I should also point out that especially for these more esoteric endocrine tumors, many patients will need to find specialty centers that are able to care for them. Especially as we see these endocrinology deserts growing, as I talked about. Right now, with 70% of counties in the country not having an endocrinologist, my biggest concern is that number is going to grow if we can't keep people interested in this field.