With that being said, let’s dive into some of what’s being presented this year. 

First up is Amylin. An entire 90-minute-deep dive on “Amylin as a Novel Diabetes and Obesity Therapy.” If you’ve been a follower of this blog you’ll know I have a sore spot with Amylin as many of the drugs in development aren’t just targeting Amylin, but also calcitonin and the calcitonin part is, in my opinion, causing all sorts of havoc. As I wrote in prior entries, the pre-clinical work shows calcitonin as beneficial, but when given to humans it is anything but! In fact it seems to drive side effects more than anything else. Hopefully this series of lectures will shine a light on some of these issues while also giving a good update to what drug candidates seem most promising. 

There are also multiple lectures and even a scheduled debate(!) about the benefits of glucagon agonists this year. If I could pick a theme this year for the conference, glucagon and amylin would be the two things getting the most airtime and significant publicity, but especially glucagon. We’ll have presentations and data for multiple glucagon agonist drugs including survodutide, mazdutide and retatrutide along with multiple preclinical drugs that incorporate glucagon as a mechanism of action. 

All the drugs!

Getting into the drug candidates will be most of the conference for me and for the rest of this article. The first is CT-868, a once daily injectable fully biased GIP/GLP-1 dual agonist in Type 1 diabetes. Roche is trialing this drug, and we actually have good data on it from Type 2 diabetics in so much that it reduces weight and lowers A1c fairly effectively, and the idea of using GLP-1 medications for Type 1 Diabetics isn’t new, as many endocrinologists already use them off label, especially for obese T1 diabetics, but we haven’t had much actual clinical trial data. Lilly is trialing Tirzepatide for Type 1 diabetes right now, but those 2 trials won’t wrap until late 2027 and mid-2028, so this will give a good look at the efficacy of another agent. The biggest downside to CT-868 is that it requires daily dosing. Regardless, getting T1 diabetics something other than insulin to help control their blood sugar is a big step forward for that disease. 

Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial | Eli Lilly and Company 

Unlocking the Next Frontier in Treatment of Obesity and Type 2 Diabetes with Retatrutide: A Triple Agonist, Activating the GIP, GLP-1 and Glucagon Receptors (TRANSCEND-T2D-1 and TRIUMPH-1 Results)

Retatrutide is the thing that most people are excited for, I expect standing room only for these presentations. I ordered custom made glucagon agonism T-shirts just for this presentation. Yes, I’m a nerd. I’ve written two articles about Triumph-1 and Transcend DM trials which are linked here. These presentations, especially Triumph-1 are going to rock the obesity medicine world. Beyond the weight loss numbers and predicting cardiometabolic marker changes, I’m personally expecting to see triglyceride reductions nearly 50%, total and LDL cholesterol reductions on par with low dose statins, so about 25-30%. Those lipid reductions alone would easily thrust retatrutide into a class of its own, but I also expect to see about a 15mmHg drop in systolic blood pressure along with a significant fraction of patients being able to stop at least 1 blood pressure medication or lipid lowering medication. I’ll also be keeping an eye out to see if they mention uric acid changes with retatrutide and especially I have my eye out for any changes in GFR/kidney function. 

The VESPER-1, -2 and -3 Trials of MET-097 (PF-08653944), an Ultra-Long-Acting GLP-1 Receptor Agonist for Weight Management

I mentioned in my preview of 2026 incretins that Pfizer had managed to purchase Semaglutide 2.0 when they acquired Metsera. I'm still on that train of thought leading up to them presenting the data on the first 3 trials of MET-097. I'm just wondering what if any differences we'll see in this data. It is a GLP1 monoagonist and as we've seen with semaglutide there's an asymptotic limit to just how much weight loss that mechanism alone can cause. Maybe the side effects are super low? Maybe the monthly dosing works? Given ALL the other things being presented at ADA I’m just not as excited about this particular drug.  

The Benefits of Glucagon/GLP-1 Receptor Dual Agonism: Insights from the SYNCHRONIZE™ Phase 3 Studies of Survodutide

Survodutide is the other GLP-1 drug with glucagon agonism and while its weight loss numbers were not nearly as wild as retatrutide, only 16.6% more on par with semaglutide, it provides yet another option for patients and allows us to compare what is a relatively strong glucagon agonist(retatrutide) versus a more ‘mild’ glucagon agonist can do, both in terms of cardiometabolic numbers, weight loss and tolerability. For me personally that's what I'm looking for, show me the liver fat reductions, change in lipids, blood pressure and kidney function that we can expect from a glucagon agonist. 

REIMAGINE 1, 2, 3: Leveraging Amylin and GLP-1 for Type 2 Diabetes Care with CagriSema

Novo Nordisk has been essentially radio silent about these 3 CagriSema trials. They announced topline data for reimagine 2 all the way back in February, it was relatively mid data. There wasn't much of a difference in A1c reduction between CagriSema and just plain semaglutide. The only good part was the weight loss. We've heard nothing about reimagine 1. And reimagine 3 was briefly mentioned in a quarterly report. If you've followed along in this blog you'll know my feelings on this and why the results are underwhelming. I'm actually extremely interested in seeing this full data as it'll help me confirm or refute some hypothetical questions I have about an unbiased Amylin/calcitonin agonist. Reimagine 3 was a trial to be used alongside basal insulin dosing and I expect that trial to show the most promising results because patients were adding back in exogenous insulin which should, ironically, make up for some of the shortcomings of calcitonin agonism. 

From Pen to Pill: Achieving a Paradigm Shift in Type 2 Diabetes—The Orforglipron 'ACHIEVE' Clinical Trial Program

While orforglipron is FDA approved for obesity, it’s not yet approved for diabetes, partially because they didn’t have all the required trial data. Lilly will be presenting data from ACHIEVE 2, 3, and 5. That is orforglipron compared to dapagliflozin, oral semaglutide and as an add-on to basal insulin. That pretty much should cover all the bases. All these trials were positive for orforglipron but now we get the gritty details including GFR/kidney data, a better look at weight loss in diabetics across 3 separate trials and what will be eventual FDA approval for diabetes.

AZD5004, A Novel Oral Small Molecule GLP-1 Receptor Agonist: Overweight/Obesity (VISTA) and Type 2 Diabetes (SOLSTICE) Phase 2 Trial Results

AZD5004 is Astra Zeneca’s submission into the non-peptide oral GLP-1 space. They've been extremely cagey and vague about both of these trials in terms of really ANYTHING. This drug is basically a clone of orforglipron (Foundayo) so results should be similar to that drug. AZ mentioned they’re taking this drug to Phase 3 so the results must have been good enough. We’ll see! 

1226-OR - Mazdutide vs. Semaglutide in Chinese Adults with Type 2 Diabetes and Obesity (DREAMS-3): A Randomised, Open-Label, Phase 3b Trial

1225-OR - Efficacy and Safety of Mazdutide 9 mg in Chinese Adults with Obesity: Results from the Phase 3 GLORY-2 Trial

I mentioned earlier that glucagon agonism is one of the themes of this conference. Finally, the rest of the world is getting on board with what I’ve been shouting about for a couple years now! With that being said Mazdutide is in a weird place as a molecule. It’s actually the very first approved GLP-1/Glucagon dual agonist, but it’s only approved in China. Eli Lilly owns the worldwide rights to the drug, and they’ve been slow walking any clinical trials of it outside China (most likely because of retatrutide) Regardless, it is an effective drug, and these two trials will show as such. We have topline data for both trials, in Dreams-3, Mazdutide was better than Semaglutide across all reported measures, namely A1c reduction and weight loss, but we don’t know the other details. The same is true for GLORY-2, average weight loss was 20.1% for the non-diabetics in the trial over 60 weeks without plateau which is tirzepatide level weight loss. It’ll be curious to see the other details and how well they match up with retatrutide and survodutide. 

1032-OR - ACCESS Trial: Dose-Ranging Evaluation of Aleniglipron, an Oral Small Molecule Nonpeptide GLP-1RA, Demonstrates Meaningful Weight Reductions in People Living with Obesity and Overweight

Aleniglipron is another non-peptide oral small molecule GLP-1 agonist, and again, we have some topline data that this drug is more effective than orforglipron and seems to approach injectable Wegovy level weight loss, but again, we don’t have the full details. This data will surely be well attended by other big pharma companies who potentially want to get in on the GLP-1 money train, especially with what appears to be a very effective agent that is ready for Phase 3 trials. 

All the posters! And even more drugs!

Moving onto poster presentations, these tend to be for up-and-coming molecules, novel research topics or smaller companies or university-based research. You can find a lot of great data and hidden bits of knowledge here. There are by my count over 3000 posters being presented. I'm trying to keep this preview article reasonable, especially because I’m going to easily write 10,000+ words about trial results, but here’s just a few of the posters that caught my eye and my brief thoughts on each. 

CT-388, a cAMP Signal-Biased GLP-1/GIP Receptor Agonist, Achieves Clinically Meaningful Weight Loss in People With Overweight/Obesity: A 48-Week Phase 2 Study [Board No. 2813]

Despite my intro, sometimes bigger companies will bury unfavorable data in the poster boards, and I have a suspicion this is the case with CT-388. Roche is the leader on this dual GIP/GLP-1 agonist and while the weight loss data has been impressive they’ve been very coy with side effect data and seeing that it’s been limited to just a poster presentation makes me suspicious that the side effect data isn’t great. Regardless, I’m all about options, so I’ll still be looking closely at whatever data they’ll have as it did lead to ~22% weight loss in phase 2. 

1733-P - Effect of Mazdutide on Kidney Function in Adults with Obesity or Overweight [Board No. 1733]

Mazdutide Improves Markers of Insulin Sensitivity in Adults with Obesity without Type 2 Diabetes [Board No. 1693]

I mentioned earlier that having so many glucagon agonists clustered in one conference will make comparisons easier, and look no further than here. There are open questions around renal function and GFR with retatrutide mostly because phase 2 data showed a rise in GFR. Now we get to see if that replicates with Mazdutide. Additionally we get to see the change in insulin sensitivity with Mazdutide as well, which should show significant improvements. 

1815-P - Efficacy and Safety of the GlP-1/GIP Dual Agonist HRS9531 in Overweight/Obese Chinese Patients with Polycystic Ovary Syndrome [Board No. 1815]

FINALLY a study on Polycystic Ovarian Syndrome(now known as Polyendocrine Metabolic Ovarian Syndrome) I don’t know what I’m looking for here, but maybe they’ll show hormonal changes, return of ovulation and normalized menstrual cycles. Regardless this sort of data is sorely needed in the realm of women’s health. 

1730-P - Zenagamtide (Amycretin), a Novel Unimolecular GLP-1 and Amylin Receptor Agonist: Phase 2b Results in T2D [Board No. 1730]

I’m not sure what to make of Novo Nordisk making this data a poster. Zenagamtide is their unimolecular Amylin/GLP-1 combo that was(is?) supposed to supplant CagriSema. They’ve got 10+ phase 3 trials running, but relegated this data to a…poster…at one of the biggest diabetes conferences in the world. Leaves me wondering if there’s something unflattering in this data. 

3083-LB - Petrelintide, a Human Amylin Analog for the Treatment of Obesity: Efficacy and Safety from the Phase 2 Trial, ZUPREME 1 [Board No. 3083]

Petrelintide reported topline data earlier in the spring. The weight loss results were pretty middling, around 10% but the big deal was there were essentially zero side effects, or at least the better way to say it is the side effect profile matched or was better than placebo for the most part. It will be interesting to see the rest of the data! 

1723-P - Semaglutide Reduces Asthma-Related Adverse Outcomes in Patients with Comorbid Asthma and Obesity: A Post Hoc Analysis of the SELECT Trial - Semaglutide Reduces Asthma-Related Adverse Outcomes

2644-P - A Phase 3 Clinical Protocol Evaluating the Safety and Efficacy of NA-931 Alone and in Combination with Oral Semaglutide for the Treatment of Obesity - 

2700-LB - High-Dose Semaglutide Is Associated with Preservation of Kidney Function in People Living with Obesity without Diabetes -

These next 3 posters are all interesting for profoundly different reasons. The first, related to semaglutide and asthma is fascinating because we know Eli Lilly is running a trial with their dual GIP/GLP-1 agonist Brenipatide for control of asthma. I’d love to know that existing agents have that effect(they should! The mechanism is the same)

The next trial NA-931 aka Bioglutide is a weird one, I can’t find evidence that it actually exists as a drug, so I’m curious how they’re managing to compare it against oral semaglutide, and that’s all I’m going to say about that.

The final one goes back to the retatrutide and mazdutide and renal function benefits. Does high dose semaglutide provide the same benefits? Do they see a GFR rise? Curious minds want to know!

3090-LB - UBT251, a Triple Hormone Receptor Agonist in Adults with Overweight or Obesity: A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 2 Trial [Board No. 3090]

UBT251 is Novo Nordisk’s answer to retatrutide and the topline data from this trial that was run in China essentially matches the weight loss seen with retatrutide. What about the side effects? What's the ratio of receptor affinity/potency? What about cholesterol, liver and all the other things we know glucagon agonism has an effect on? Unlike the Zengamatide data, I’m not surprised to see this on a poster board, because we need global phase 2 trials, which are ongoing. 

1666-P - Orforglipron and Markers of Insulin Sensitivity and Beta-Cell Function by Prediabetes Status in Adults with Obesity: A Post Hoc Analysis of the ATTAIN-1 Trial [Board No. 1666]

1716-P - Menopausal Stage and Weight Outcomes with Orforglipron vs. Placebo: Post Hoc Subgroup Analysis from ATTAIN-1 and ATTAIN-2 [Board No. 1716]

The final bit of interesting data is on Foundayo (orforglipron) the insulin sensitivity data and beta cell function poster will be fascinating peer under the hood to see how orforglipron is working, especially because it is a biased GLP-1 agonist with minimal beta arrestin activity (beta arrestin is appropriately named as it ‘arrests’ activation of the receptor to oversimplify it.) 

The other poster is about women’s health again (waves tiny flag) and looks at weight outcomes based on menopause status with orforglipron, this is also an important data set because female weight GAIN often happens with menopause. Lilly let out a press release stating average weight loss was 14% in menopausal women but didn’t mention premenopausal weight loss, hopefully it’s similar.

So that’s a quick and dirty preview of ADA 2026, did I leave out a whole bunch of stuff? Absolutely.

But rest assured, I’ll be writing many thousands of words in the next few weeks. It's about to be Incretin Christmas in June! Stay Tuned! Articles will be dropping as fast as I can write them over the next couple weeks. 

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