ADA 2025: Insights, highlights and more

Highlights from the ADA 2025 Conference

Whoever said “It was like drinking from a fire hose” must have just attended an ADA Scientific Sessions.  Because that’s exactly what it felt like participating in the 8000-attendee conference in Chicago for the past four days.  Between the panel presentations, research posters, product theaters and exhibit hall displays, my brain feels completely saturated. 

So before anything important leaks into oblivion, I wanted to share some of the highlights from the meeting.

I. Working Towards a Cure:  Islet Cell Therapies

(note: this information was presented at the DiabetesMine D-Data ExChange, which took place off-site concurrently with the ADA Scientific Sessions)

Several companies are working on innovative approaches to preserving/replacing insulin-producing cells with minimal immunosuppression.

• Sernova has developed a protective pouch containing islet cells, placed in the abdominal fat layer. Immunosuppression is only required for four weeks. The outer framework of the pouch is removed after enough time has passed to allow development of adequate blood flow to nourish the cells. This is key to helping ensure the long-term survival of the cells within the pouch – something that has doomed many other pouch implant procedures.

• Sana Biotechnology is applying an approach similar to an embryonic sac, which protects a developing fetus from immune attack. Cells transplanted in the forearm are treated with enzymes designed to make them “hypo-immune” and resistant to damage from the immune system. This approach has resulted in measurable insulin production after 12 weeks with no immunosuppression.

• Symbio Cell Tech is using large quantities of MSCs (mesenchymal stem cells) to protect transplanted islets from immune system attack without the need for immunosuppression. A single donor can provide literally hundreds of therapeutic doses of MSCs. The procedure involves a simple outpatient infusion that has proven effective in mice and dogs.

II. Drugs, Drugs and More Drugs

• There is renewed interest in the amylin hormone (which is co-secreted in a 1:15 ratio with insulin by functioning beta cells).  Which is curious, given that Bristol Myers-Squibb recently announced that it will be discontinuing production of the only commercially-available form of amylin (Symlin) later this year. Why the renewed interest? Apparently, amylin does more than just slow gastric emptying, block glucagon secretion and make people a bit nauseous. Apparently, it also promotes calcium uptake by bone (sharing similar properties to the hormone calcitonin) and increases the brain’s response to the hormone leptin, which further promotes satiety.

Investigators believe that combining modest doses of amylin with other hormones can facilitate weight loss with fewer side effets. An oral medication, amycretin, is a combination of amylin and a GLP-1 receptor agonist. In early trials, a single daily dose given with a meal produced 13% weight loss in just 12 weeks. An injectable form of amycretin, given once weekly, produced 16% weight loss in 28 weeks, and 22% in 36 weeks.  Cagrsema, another amylin/GLP-1 combo given by injection once weekly, produced 23% weight loss in 60 weeks. And petrelinitide, a combination of amylin and calcitonin, produced 5-8% weight loss in 16 weeks when injected weekly, with side-effects similar to placebo.

• Use of GLP-1 and SGLT-2 meds in conjunction with AID systems was the focus of discussion at a special session. With nearly 10% of AID system users (most of whom have T1D) using one of these medications in an off-label fashion for weight reduction, appetite suppression and/or glucose reduction, it is important to learn all we can about how to use them safely.  GLP-1 receptor agonists certainly increase the risk of hypoglycemia when taken with insulin, and high doses may lead to ketosis due to reductions in carb intake and insulin doses. Nausea is common with GLP-1 use, so experts recommend keeping an antiemetic medication such as Zofran on-hand. Glucose management approaches vary, but success has been seen with a modest (10-20%) reduction in basal and bolus insulin on systems that allow such adjustments, particularly during the first two months of GLP-1 use. With long-term use and continued weight loss, basal doses may require further reduction.

Because of the increased risk of DKA with SGLT-2 inhibitor use, people with T1D are encouraged to monitor blood ketones twice daily during the first two weeks of use, and with any unexplained hyperglycemia thereafter. In one study, total daily insulin requirements came down according to medication type and dose:

Interesting to note: dapagliflozin and empaglifozin use led to more basal insulin reductions, while sotagliflozin use led to more bolus reduction.

• Switching gears, the blood pressure medication verapamil, a widely-used calcium channel blocker, was studied to see if it can improve and prolong beta cell function in people with newly-diagnosed T1D. Verapamil has been shown to normalize autoantigens believed to preserve beta cell health. In previous studies, verapamil was reduced c-peptide decline for up to one year following T1D diagnosis (indicating greater insulin production by remaining beta cells). Long-term follow-up has shown no increase in side effects compared to placebo. However, verapamil must be used cautiously as it can contribute to other health complications.

• Researchers in Austria and the UK are testing a new ultra-concentrated form of aspart (Novolog/Novorapid). U-500 aspart has five times the potency of traditional U-100 insulin, so much smaller doses can be administered – a significant advantage for people who require high doses due to insulin resistance. The concentrated insulin, given the sexy name AT-278, starts working and peaks a little earlier than traditional rapid-acting insulin – a stark contrast to the very slow action of U-500 Regular insulin that has been used in the past for people with extreme insulin resistance. Researchers observed that the rapid action of AT-278 persists regardless of body size.

• Although not approved for use in the treatment of type-1 diabetes because of an increased risk of ketoacidosis, SGLT-2 inhibitors are still prescribed in some cases for their glucose-lowering and heart & kidney benefits. A recent study at Joslin Diabetes Center and Harvard Medical School evaluated the impact of SGLT-2 inhibitor use among approximately 100 adults with T1D for six to 24 months. The results were mixed. Participants experienced a significant reduction in A1c throughout the study, but no changes were seen in kidney function or blood pressure, and two people dropped out due to ketoacidosis.

III. On the Tech Front

• Efforts continue to develop an automated insulin-delivery system that does not require the user to bolus at mealtimes. Various algorithms have been tested, but none is able to match the degree of glucose control achieved when the user administers pre-meal boluses. The closest was able to achieve 63% time in-range (70-180mg/dl) by making the up-front portion of an automated bolus as aggressive as possible without causing hypoglycemia.

(I don’t know about you, but I feel that if we put half as much effort into behavioral research to improve the probability of bolusing for meals, we could have this issue solved a lot sooner)

• For those who find carb counting to be a general nuisance (like who doesn’t?), good news. One published study found that users of Medtronic’s 780G advanced AID algorithm achieved 75% time-in-range when only entering a single “fixed” carb amount whenever eating, compared to 80% by those who varied the carb entry based on the amount consumed. Researchers at the Barbara Davis Center in Colorado reported similar time in-range (around 66%) and time below-range (2%) by AID users who entered 30/60/90g carb amounts compared to those who performed more detailed carb counting. So if carb counting has you confused or burned out, or if it keeps you from bolusing at meal/snack times, consider a simpler, fixed-amount entry.

• Having launched the first extended-wear infusion set a couple of years ago, Medtronic (now MiniMed) collected user data to evaluate the effectiveness of the set in the real world. Compared to standard infusion sets (worn for 3 days), users of extended wear sets (worn for 7 days) experienced greater time in-range (75.4% vs 74.7%) and fewer occlusions per 100 days (3.3 vs 4.1).  In addition, almost no dropoff in performance was seen on the final days of the 7-day wear cycle with the extended wear set.

• Rapid change in glucose levels, a component of glucose variability, is associated with long-term blood vessel damage as well as physical/emotional discomfort. A group in Vancouver, Canada studied the impact of open-source (DIY) automated insulin delivery systems on the degree to which users experience rapid changes in glucose levels throughout the day. They found a significant (?20 minutes/day) reduction in time spent in a state of rapid rise or fall when switching from standard pump/CGM use to an open-source algorithm. The benefit was greatest for those who entered the study with sub-optimal glycemic management (time in-range <50%). Whether this benefit is seen with commercially-available AID systems is not known.

• While on the topic of automated insulin delivery, many have wondered whether using “ultra-rapid” insulin (Fiasp and Lyumjev) is any better using traditional rapid-acting insulin in AID systems.  The answer is yes, but just a little. Data experts in China analyzed more than a dozen research studies on the topic and found that users of ultra-rapid insulin spend 1.4% more time within target range and 0.3% less time below target. While these may seem like minor improvements, consider that the cost and side-effects associated with ultra-rapid insulin are virtually identical to rapid insulin, so why not use it?

IV. Cool New Stuff

• Eversense recently launched their one-year implanted-below-the-skin CGM. And now, Sequel (makes of the soon-to-be-released Twiist pump) have announced that they will integrate the Eversense CGM into its AID system. What could be better? Well, how about a THREE-year CGM? Glucotrack is a continuous blood-glucose monitor with a three-year lifespan. That’s right… instead of measuring glucose in the fat layer below the skin, it measures glucose directly in the bloodstream.The sensor, attached to a Bluetooth transmission device by way of a thin tube, is inserted into a vein in the upper chest; the transmitter rests just below the skin. The insertion procedure takes about 30 minutes under local anesthetic, and is performed on an outpatient basis at a catheterization lab (similar to a pacemaker procedure). There is nothing to wear on the body, and the system does not require any charging. The manufacturer reports very good accuracy (MARD 7.7%); calibration requirements are still to be determined. The long-term venous-implanted design eliminates common CGM issues such as lag time, compression lows, warmup times, and accidental displacement. Pivotal studies are now underway in Australia. US studies are expected to commence in mid-2026.

• OK, now you know about CGM and CBGM. Here’s another one:  CKM. What’s the K for? Ketones! Abbott is expanding the capabilities of its Libre CGM by adding a ketone measurement analyte to the glucose sensor. The specific molecule being measured is beta-hydroxybutyrate – an acidic bi-product of fat metabolism that builds up to toxic levels when the body becomes insulin-deficient. About 80% of ketones produced take the form of beta-hydroxybutyrate; the remainder is acetoacetate. Early study results show a very strong correlation between the sensor’s interstitial ketone measurements and values taken with a blood-ketone meter. In fact, elevated ketones may be detected even before glucose levels rise from insulin deficiency during illness and injury.  And since blood ketones appear approximately 2 hours before ketones appear in the urine (and urine strips miss the presence of ketones about 25% of the time), CKM can be very valuable in preventing DKA.

Ultimately, the system will transmit both glucose and ketone measurements to a phone app, with customizable alert thresholds for each. This is good news for everyone with T1D, especially those at increased risk of DKA:

• Women
• Immigrants
• Those with a high A1c
• Insulin-resistant individuals
• Ages 10-14
• Users of SGLT-2 inhibitors

Experts are looking at possible alert thresholds to set and the possibility of rate-of-change alerts since most people have a small amount of ketones present almost all the time, but a rise of >2 mmol/l per hour is considered dangerous. The consensus recommends the following categories for ketone levels:

• <.6  (normal)
• .6-1.5 (elevated)
• 1.6-3.0 (high)
• >3.0 (urgent high)

Pivotal trial research on Abbott’s CKM showed an average baseline ketone level of 0.3 mmol/l. After suspending participants’ insulin pumps for up to six hours, ketone levels peaked at 1.8 in adults, 2.25 in kids. Interestingly, 35% of subjects had ketone levels greater than 1 before glucose levels exceded 250 mg/dl.

Once approved, Abbott is planning to integrate their dual CGM/CKM with pump/AID systems from Tandem, Sequel, Beta-Bionics and Ypsomed.

• Dexcom has updated its G7 app to include a meal photo feature. In addition to logging the photos on the trendgraph, the system can be configured to display glucose values that follow the meal simply by clicking on the photo. Dexcom is also planning to utilize AI to derive nutrient information (including carb counts) from the photos. For now, only the photo-logging feature is available. To access it, update your G7 app to version 2.9.0 in your app store.

• Lipohypertrophy, a buildup of thick, fibrotic fat tissue below the skin, has been a problem for insulin users since insulin was discovered. Once it develops, it causes problems with insulin absorption, and it never goes away. Or does it?  Neodyne Biosciences has developed a skin patch called Embrace which uses a repeated constriction/expansion process to not only prevent the development of lipohypertrophy, but also provide some relief to existing cases. The FDA-approved patches are worn for 15 days at a time and come in various sizes. For more information, visit www.embracediabetescare.com.

• Anyone who has dealt with the recent summer heat waves knows that insulin spoilage is becoming a more common issue. To help detect potential exposure to insulin-destroying temperatures, a Scandivavial company has developed InsulinSaver: a thumbdrive (or Hershey Miniature)-sized device that alerts the user with a flashing light whenever the temperature exceeds or goes below temps that are recommended by the insulin manufacturers. It has a 12-18 month battery life and can easily be placed next to pens/vials or stuck to an insulin pump with a piece of tape or velcro. Visit www.insulinsaver.com for more information.

V. The Kids Are Alright

• Several presentations focused on progress and innovation in pediatric type-1 diabetes care. On a highly positive note, the incidence of diabetic ketoacidosis (DKA) in children is down in recent years, particularly among insulin pump users. This may be related to better infusion set design, less incidence of clogging/occlusions, and perhaps better education on proper troubleshooting. Interestingly, DKA is slightly more common among users of AID systems – perhaps related to users’ tendency to rely (too) heavily on the system to fix hyperglycemia.

• Studies on the use of Afrezza inhaled insulin in children showed that it works as well as injections of insulin. The very rapid action of inhaled insulin is even more pronounced in children, clearing in approximately 60 minutes at low doses (4 Afrezza units), 90 minutes at medium doses (8 units) and 120 minutes at higher doses (12u). Researchers compared users of multiple daily injections of rapid-acting insulin (MDI) to use of Afrezza at mealtimes over a 26-week period.  Here are the results:
• A1c was slightly higher among Afrezza
• Time-in-range was similar for both groups
• Post-meal glucose peaks were approximately 40 mg/dl lower among Afrezza users
• Treatment satisfaction improved with Afrezza use
• No differences were seen in frequency of hypoglycemia or episodes of DKA or severe hypoglycemia
• Both groups saw similar, very minor changes in FEV (lung function)

At present, Afrezza is only approved for use in adults, but it may be prescribed “off label for use in children.

• One of the “adjunct” medications studied in children for potential benefit and safety issues was the SGLT-2 inhibitor dapaglifozin. SGLT-2 inhibitors promote excretion of sugar in the urine. They are commonly used in the treatment of type-2 diabetes, but the FDA has denied approval for use in type-1s due to an increased risk of ketoacidosis. The ATTEMPT study examined the effects of a low dose of dapagliflozin administered for 22 weeks to teenagers. To mitigate the risk of DKA, participants were educated on risk-prevention strategies. Preliminary results revealed the following:

• An average weight loss of 2.8kg (about 6 lbs)
• A1c came down 0.5%
• Time in-range increased by 9%
• Improvements were seen in kidney function (glomerular filtration rate)
• No increase was seen in adverse events such as hypoglycemia and urinary tract infections
• No increase was seen in episodes of DKA

VI. Better Living

• Although dietary protein does not usually convert directly into glucose, it can cause the pancreas to secrete glucagon, which in turn stimulates the liver to release glucose into the bloodstream.  With this in mind, investigators took a look at whether protein ingestion prior to a workout can reduce the risk of hypoglycemia. The answer:  YES.  Taking a modest dose of whey protein 30 minutes prior to a 60-minute moderate-intensity cycling session resulted in stable glucose levels during and 90-minutes post workout (see the graph below). However, there was a glucose decline 2-3 hours post-workout, perhaps related to depletion of liver glycogen. So if you want to avoid carbs (and a temporary glucose spike) pre-workout, consider protein instead.

• Foot complications are often thought of as a problem reserved for older people with type-2 diabetes who have circulatory problems. Not true, according to a recent study conducted at Grady Health System in Atlanta. Analysis of patients admitted for foot ulcers found no difference in the rate of ulceration among people with type-1 versus type-2 diabetes. The same can be said for the rate of amputation. The one difference: those with type-1 were younger and had much higher A1c levels at the time foot ulcers developed.

• Diabetes Self-Management Education and Support (DSMES) is recognized as valuable but under-utilized, with fewer than 10% of all people with diabetes receiving such services. DSMES programs provide proactive glucose management as well as preventive healthcare guidance. A CDC-sponsored study examined the impact of DSMES on healthcare utilization, specifically ER visits, hospital admissions after ER visits, and preventive care visits (primary, podiatry, and vision). Compared to a matched comparison group who did not receive DSMES, recipients experienced 25% fewer hospitalizations and 50% fewer ER visits, while preventive care visits for eye and foot care were significantly greater. Given the costs (in terms of dollars and quality of life) for those who experience diabetes-related complications, DSMES has once again proven its immense worth.

• Researchers in Vancouver, Canada decided to investigate the theory that water is better than diet beverages for weight loss. Women with type-2 diabetes were assigned to either have their usual diet beverages in the afternoon or just water for 18 months. The water-only group lost 2kg more than the diet beverage consumers, and also saw greater improvements in fasting glucose, insulin sensivity, 2-hour postmeal glucose and serum triglyceride levels.

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