Transcript
Dr. Neal Skolnick (0:02)
Welcome to Diabetes Core Update January 2026. I'm your host, Dr. Neal Skolnick and joining me is my co host Dr. John Russell. And we have another excellent series of articles this month, beginning with an article from the New England journal on the PCSK9 IVlocumab in patients without previous MIS or strokes and the effect on mace. Then an article from JAMA on SGLT2 inhibitors and kidney outcomes looked at by EGFR and albuminuria. Then from diabetes care, continuous SGLT2 GLP1 receptor agonists and their effect on frailty progression in older adults with type 2 diabetes, an incredibly important issue. Then an article from JAMA on The effects of SGLT2 inhibitors by diabetes status and level of albuminuria. Then we're going to talk about an important article in Diabetes Care on tirzepatide in adults with type 1 diabetes. And this is a phase 2 randomized placebo controlled trial. And finally a fascinating article from Diabetes Care titled Listening. Yes, I said listening to hypoglycemia and this is using voice as a biomarker for detection of medical emergencies of hypoglycemia using a machine learning algorithm.
Dr. John Russell (1:58)
Let's jump in our first three articles from the New England Journal of Medicine and it looked at evoloquimab in patients without a previous MI or stroke. So in this particular study it was an international double blind randomized placebo controlled trial of evolocumab in patients with atherosclerosis or diabetes without a previous MI or stroke who had an LDL of at least 90 milligrams per deciliter. Patients were randomly assigned in one to one ratio to receive either the evolocumab at a dose of 140mg every two weeks or placebo. The two primary endpoints were a composite of death from coronary heart disease, myocardial infarction or ischemic stroke. That would be a three point MACE or composite of three point MACE or ischemic driven arterial vascularization, which would be a four point mace. There were over 12,000 patients who were randomly assigned to receive either evolocumab or placebo and they were included in efficacy analysis. The median age of the patients was 66 years of age, 43% were women and 93% of the patients were white. The median follow up was 4.6 years. A three point MACE event occurred in 336 patients, or 6.2% in the evolocamab group, as compared with 443 or 8% in the placebo group with a hazard ratio of 0.75. A four point MACE event occurred in 747 patients or 13% in the evolocumab group as opposed to 907, which would be 16.2% in the placebo group with a Hazard Ratio of 0.81. There was no evidence of between group difference seen in the incidence of safety events. Neil?
Dr. Neal Skolnick (3:52)
John, this is such an important trial. Recent guidelines have talked about lower and lower LDL goals and we'll talk about them in a moment. But for people at high risk and high risk have been defined as people with diabetes and people with existent underlying atherosclerotic disease. Most of these trials, at least in the PCSK 9s, all of the trials were in people who had had events. It is so helpful now to be able to know from the evidence that we can help people substantially who have significant elevated risk by virtue of either atherosclerotic disease that is established by something as simple as something John, you and I are doing every week, which are calcium scores. A calcium score over 100 opted someone in to this study as having underlying atherosclerotic disease. And the other group that's very common that we see in the office all the time are people with high, high risk diabetes. The other thing that's interesting, in this trial, in addition to a 25% decrease in mace, there was a 20% decrease in death from any cause and that was 7.9% in the treated group, 9.7% in the placebo group. That was a hazard ratio of 0.8 and it had a confidence interval of 0.70 to 0.91. Now you see that doesn't pass unity. If this wasn't low on the hierarchical analysis level, where one of the ones above it didn't meet statistical significance, this would have opted in for statistical significance. But because of the way statistics are done in clinical trials, where things are predefined, which is very important, this can only be thought thought of as hypothesis generating. Nonetheless, this is a powerful effect. Death from any cause and in all likelihood represents truth. So what does this tell us? Well, guidelines have recommended progressively lower levels for LDL with a cholesterol less than 70. Now recommended by the American Diabetes association for people with diabetes and by the American heart association in 2022 less than 55 for at very high risk. You usually can't get there with a statin alone. You sometimes get there with statin plus ezetimab. I think we are way underutilizing PCSK9s and this trial is going to be important in putting that to the forefront of our attention and establishing the evidence base to treat more people with PCSK9s who don't have LDLs below those low goals. Our next article from JAMA is a Meta analysis of SGLT2 outcomes and the importance of this trial was that SGLT2 inhibitors reduce CKD progression in individuals with type 2 diabetes, CKD or heart failure. However, their effects in people with stage 4 CKD or who have little to no albuminuria remains unclear. They assessed in this trial a large Meta analysis of SGLT2 inhibitor trials from the Cardiorenal Trialist Consortium. These were all randomized double blind placebo controlled trials and what they found among over 70,000 participants average age 65 years of age in 10 randomized trials, 3.3% experienced CKD progression and 1.4% reached kidney failure. SGLT2 inhibitors reduced the risk of CKD progression with a hazard ratio of approximately 0.56, that is a 40% decrease irrespective of baseline EGFR and irrespective of baseline albuminuria. Although the magnitude of protection varied, SGLT2 inhibitors reduced the annual rate of EGFR decline across all EGFR and UACR subgroups, including participants with and without diabetes.