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ADA 2023
An Expert’s Guide to ADA 2023: Pearls and Takeaways

Released: July 10, 2023

Payal Kohli
Payal Kohli, MD, FACC
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Key Takeaways
  • In a subgroup analysis of the CLEAR Outcomes trial, bempedoic acid reduced 4-point MACE in high-risk primary prevention patients.
  • Oral and novel GLP-1 RAs may provide patients with additional options to reduce their weight when injections with traditional GLP-1 RAs are a barrier.
  • When used in combination, SGLT-2 inhibitors and GLP-1 RAs can further reduce cardiovascular risk post-myocardial infarction and improve patient outcomes.

New and Emerging Agents

The Primary Prevention Cohort of the CLEAR Outcomes Trial
The CLEAR Outcomes trial evaluated bempedoic acid vs placebo in patients who were statin intolerant. Although the overall results of the trial were initially presented at American College of Cardiology 2023, at American Diabetes Association (ADA) 2023 we saw the results from the primary prevention cohort, which was made up of high-risk patients and accounted for roughly one third of the trial enrollment. These individuals had an LDL-C >100 mg/dL, a Reynolds Risk Score of >30%, type 1 or type 2 diabetes, or a high calcium score, landing them in the high-risk primary prevention group.

In the parent trial there was a roughly 13% reduction in the 4-component major adverse cardiovascular events (MACE), which was a composite of cardiovascular (CV) death, myocardial infarction (MI), stroke, and coronary revascularization. When we look at the primary prevention cohort, there was a 30% reduction in the same endpoint. If we dive in a bit further, we’ll see that the 3-component MACE had a 36% reduction (CV death, MI, and stroke). What really drove many of these reductions in the 3- and 4-component MACE was a reduction in MIs, of 39%. This is incredible because we’re talking about a population that has largely been left untreated in the past when found to be statin intolerant.

Oral and Novel GLP-1 RAs for Weight Loss
Over the last couple of years, there has been a revolution in the treatment of obesity. We have shifted away from thinking about obesity as a behavioral problem and starting to focus on obesity as a physiologic problem. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)  have been a game changer in this respect. The drawback of these medications has been that they're injectable, which has been a barrier for many people. So there has been what I like to call a nuclear arms race to develop oral GLP-1 RAs. Due to this, we saw data on 3 oral GLP-1 RAs presented at ADA: semaglutide, orforglipron, and danuglipron. Oral semaglutide demonstrated a 15% loss of body weight, which is comparable to injectable GLP-1 RAs, with mild to moderate side effects. At the highest dose of orforglipron there was an approximately 15% reduction in weight with, again, a side effect profile that was very similar to the injectable agents. Danuglipron also demonstrated a roughly 15% reduction in weight with similar efficacy to the injectables and a similar side effect profile and tolerability. With orforglipron and danuglipron applying for FDA approval in late 2023, we may see expanding oral GLP-1 options to improve access to weight loss medications.

Retatrutide Triple Agonist
The new science that came out of this meeting that had everybody on the edge of their seats was a drug called retatrutide, which is a triple agonist—a combination of a GLP-1 RA, GIP, and glucagon. The reason this is novel is because now we're hitting the hormonal pathway from multiple different targets. We saw a 24% average weight loss with this medication, with some patients in the trial having as much as a 30% weight loss. Putting it all together we can see that treatment of obesity from a pharmacologic perspective is making tremendous strides.

Nutrition and Implementation Science to Improve Patient Outcomes

SGLT-2 Inhibitors and GLP-1 RAs
What happens when you combine sodium-glucose cotransporter-2 (SGLT-2) inhibitors and GLP-1 RAs? A study of a UK database from 2013 to 2020 evaluated almost 9000 patients who received both medications. They compared taking an SGLT-2 inhibitor alone vs the combination to see if MACE events were improved. Remarkably, there were whopping reductions of 34% in the 3-component MACE, which was CV death, MI, and stroke, primarily driven by reductions in MI. What this tells me is that use of these medications together is associated with a much lower CV risk. Is this because of the mechanism of the drugs? Increased compliance? Or access to care? Probably all of those factors, but these results tell me we need to use combination therapy.

Data Outcomes of a Study on SGLT-2 Inhibitors and GLP-1 RAs
There was also a study evaluating patients with diabetes who were prescribed GLP-1 RAs and SGLT-2 inhibitors at time of discharge after an MI, and how it impacted whether they stayed on these medications. This was a single-center study from an urban teaching center with low-income patients. It evaluated 178 patients with a 1-year follow-up and saw that only 39% of these patients got an SGLT-2 inhibitor at discharge, and only 8% got a GLP-1 RA. After an MI, you want to hit CV risk reduction from multiple pathways; this demonstrates that we are not utilizing these medications enough at baseline. But for patients who were prescribed these medications at discharge, the likelihood of staying on this medication a year later was 2.6-fold higher for SGLT-2 inhibitors and 10.9-fold higher for GLP-1 RAs. So we need to start thinking about prescribing multiple risk reduction medications at the time of discharge to improve patients’ chances of remaining on these medications.

Nutrition Science
Now let's talk about nutrition because that is something my patients often ask me about in my practice. During the conference we examined how to discuss portion control with patients as a strategy to lose weight. It turns out we need to go beyond portions and discuss the energy density of the food we eat and the importance of varying what we eat, which is more likely to allow us to be able to lose weight. There was also a study about dietary records evaluating a smartphone app and looking at artificial intelligence (AI) to see whether an app could appropriately assess what you're eating vs AI plus dietitians. To no one’s surprise, the apps are not that good at knowing what we're eating. Although they can be part of tracking dietary behaviors, you can’t hang your hat on them because when dietitians were involved in doing the analysis, the results were much more accurate.

These were some of the exciting takeaways from the ADA Scientific Sessions 2023 that you can implement in your practice.

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