Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives

Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives

By Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives

Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives is a podcast hosted by Drs. Diana Isaacs and Natalie Bellini aimed at providing a regular roundup of the latest clinically ap... more

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Best of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives

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  1. Number 1: Ultra-rapid insulin, IcoSema advance in type 2 diabetes

    Insulin-resistant patients with type 2 diabetes who require high-dose therapy have long lacked a rapid-acting option concentrated enough for compact insulin pumps. New pharmacokinetic data on an ultra-rapid U-500 insulin aspart, alongside additional phase 3 results for a combined once-weekly insulin icodec-semaglutide regimen, both aim to close persistent gaps in insulin delivery for this population. In this episode of Diabetes Dialogue, hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, reviewed two studies addressing unmet needs in insulin therapy for type 2 diabetes. The investigational agent AT278 is a highly concentrated insulin aspart formulated at 500 units/mL, distinct from existing U-500 regular human insulin, which behaves more like an intermediate-acting product. In a single-center, randomized, double-blind, crossover euglycemic clamp study spanning body mass index from 25 to 38 kg/m², AT278 produced significantly faster absorption and a greater glucose-lowering effect within the first hour versus both standard U-100 insulin aspart and U-500 regular human insulin. The ultra-rapid pharmacokinetic and pharmacodynamic profile held consistent across the BMI range studied. Current U-500 regular insulin requires dosing 30 minutes before meals while simultaneously serving as basal and prandial coverage, complicating use in automated insulin delivery systems and limiting compatibility with smaller-volume pumps. A concentrated, rapid-onset formulation could allow patients with high insulin requirements to use compact pumps and extended-wear infusion sets without the absorption problems tied to large-volume subcutaneous depots. Drawn from an early-phase study, the findings position AT278 as a potential first ultra-rapid option for prandial dosing in this population, though regulatory approval for pump use remains undefined. Separately, the phase 3 COMBINE 4 trial evaluated a fixed combination of once-weekly insulin icodec (Awiqli) and semaglutide, known as IcoSema, against once-daily insulin glargine U-100 in 485 adults with type 2 diabetes and baseline A1C above 8%. Over 40 weeks, IcoSema reduced A1C by 3.32 percentage points versus 2.44 points with glargine, a between-group difference of 0.88 percentage points, while producing a 0.79 kg weight reduction compared with a 3.81 kg gain with glargine. Time in range reached 79.8% with IcoSema versus 64.5% with glargine, consistent with the mechanistic rationale of pairing glucagon-like peptide-1 receptor agonism with basal insulin to limit postprandial excursions. These results build on earlier COMBINE 1 through 3 data, which showed IcoSema achieving noninferior or superior A1C reduction, superior weight outcomes, and lower hypoglycemia rates versus comparators. A single weekly injection combining basal insulin with a GLP-1 receptor agonist could reduce treatment burden and consolidate pharmacy copays, though semaglutide exposure remains capped by concurrent insulin titration, averaging 0.66 mg in COMBINE 4. Whether either agent reaches United States practice, including reported uncertainty around a domestic IcoSema launch, will determine their eventual role in managing insulin-resistant type 2 diabetes.

    22min
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  2. Number 2: Tech, Screening, and Care Highlights from ADCES 2026

    Advances in diabetes care rarely arrive through a single channel, and the 2026 annual meeting of the Association of Diabetes Care and Education Specialists (ADCES) reflected this breadth, with new insulin delivery hardware, cardiometabolic risk management, and endocrine screening criteria all drawing attention from clinicians in Columbus, Ohio. On a recent episode of Diabetes Dialogue, recorded on-site at ADCES26, co-hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, reviewed sessions and exhibits spanning insulin delivery technology, cardio-kidney-metabolic (CKM) risk reduction, beta-cell preservation, ketone monitoring, and hypercortisolism screening. On the exhibit floor, 2 simplified insulin delivery devices signaled a push toward patients still managing diabetes on multiple daily injections. Pivot, a tubeless patch pump from Modular Medical, holds up to 300 units of insulin, delivers preset 2-unit boluses, and supports 2 distinct basal rates, though it is not yet an automated insulin delivery (AID) system. CeQur's Simplicity bolus-only patch has moved toward 7-day wear with up to 240 units of capacity and a one-unit dosing option, positioning it alongside once-weekly basal and incretin therapies on a shared weekly schedule. A case-based session on CKM syndrome, built around a patient newly diagnosed with type 2 diabetes and discharged on insulin without pen needles, illustrated how risk calculators such as PREVENT can guide therapy beyond glycemic control. The case incorporated glucose-lowering therapy alongside GLP-1 and SGLT2 inhibitor use for cardiorenal protection, discontinuation of an unindicated beta blocker masking hypoglycemia symptoms, and a plan to taper insulin as other agents took effect. A separate discussion focused on C-peptide, a marker of residual endogenous insulin production, as an emerging clinical trial endpoint in type 1 diabetes. Patients who retain measurable C-peptide despite long-standing autoimmune beta cell loss appear to experience fewer cardiovascular events, less diabetic ketoacidosis, and less severe hypoglycemia, reinforcing interest in beta-cell-preserving therapies during early-stage disease. Continuous ketone monitoring, an emerging sensor category, was covered through patient cases including pregnancy-related nutritional ketosis and a case of latent autoimmune diabetes in adults treated with an SGLT2 inhibitor without insulin, a combination carrying risk for euglycemic diabetic ketoacidosis. The hosts noted real-time ketone data could eventually clarify when SGLT2 inhibitor use is appropriate in insulin-requiring patients despite this risk. A well-attended early-morning session addressed hypercortisolism as an underrecognized driver of treatment-resistant hypertension and hyperglycemia. Updated American College of Endocrinology guidance now recommends screening when hemoglobin A1c remains >7.5% or blood pressure remains uncontrolled despite maximal glucagon-like peptide-1, SGLT2 inhibitor, and multidrug antihypertensive therapy, with diabetes care and education specialists playing a growing role in identifying candidates and coordinating referral. The hosts also highlighted Blue Circle Health, a nonprofit offering ≤6 months of virtual bridge care, including dietitian visits, social work support, and insurance navigation, for people with type 1 diabetes across 20 states. Collectively, the sessions underscored a field advancing simultaneously on device design, risk stratification, biomarker science, and access to supportive care.

    17min
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  3. Number 3: Diabetes Dialogue: Retatrutide Phase 3 Data Show Major Weight Loss

    Welcome back to Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives! Triple hormone receptor agonism is emerging as a frontier in metabolic disease treatment, and topline phase 3 results for retatrutide suggest the strategy can push weight loss and glycemic control beyond current incretin therapies, even as a separate JAMA analysis raises questions about oversight in online GLP-1 prescribing.1,2 On the latest episode of Diabetes Dialogue, hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, reviewed topline results from the TRIUMPH-2 and TRIUMPH-3 trials of retatrutide, a glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptor triple agonist. TRIUMPH-2 enrolled 1000 participants with type 2 diabetes across 98 centers and tested 4 mg, 9 mg, and 12 mg doses against placebo over 80 weeks. The 12 mg dose produced weight loss up to 21% from a baseline of 106 kg, or roughly 23 kg. Hemoglobin A1C fell between 1.4 and 1.6 percentage points from a baseline of 7.7%, versus 0.2 points with placebo, a large glycemic effect given the near-normal starting A1C and discontinuation of 14% at the highest dose. TRIUMPH-3 enrolled over 1900 participants with class II or III obesity (body mass index of 35 or higher) and established cardiovascular disease, randomized to 9 mg, 12 mg, or placebo over 80 weeks. The 12 mg dose delivered 23% weight loss versus 3% with placebo, alongside a 37% reduction in triglycerides, 17% reduction in non-high-density lipoprotein cholesterol, and 9.3 mmHg reduction in systolic blood pressure. Major adverse cardiovascular event outcomes trended favorably but did not reach significance, an expected limitation of an 80-week trial. Gastrointestinal effects were common across both trials, including diarrhea in up to 34% of participants and nausea in up to 28%, consistent with the broader incretin class. Isaacs and Bellini also discussed a JAMA secret-shopper study, led by Ashwin Chetty, MD, examining online GLP-1 prescribing across 49 telehealth websites. Of these, 92% prescribed the requested medication and 70% mailed it, often without required photo verification, blood work, or clinician video visits, in some cases within five minutes. Compounded formulations, including unproven sublingual drops, were frequently offered alongside add-on supplements marketed as personalization, a workaround linked to compounding rules requiring documented medical need. Together, the findings illustrate a widening gap between the therapeutic ceiling GLP-1-based agents are reaching in controlled trials and the variable oversight surrounding real-world access to these drugs, underscoring the need for clinicians to proactively screen patients for unsupervised use. Editors’ Note: Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others. Bellini reports disclosures with Abbott Diabetes Care, MannKind, Povention Bio, and others.

    25min
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  4. Number 4: Evolving Wearable Insulin Delivery Devices - AID, CGM, and More

    To begin the episode, cohosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss the rapidly evolving landscape of wearable insulin delivery, focusing on recent developments in patch pump technology and the growing number of tubeless insulin delivery systems entering the market. The conversation centers on the recent FDA clearance of the Pivot patch pump from Modular Medical, which the hosts describe as an important addition to a field that has historically been dominated by a single tubeless option. Isaacs reviews the design of the Pivot system, explaining that while it is a tubeless insulin pump, it differs from current automated insulin delivery (AID) systems because it does not communicate with a continuous glucose monitor (CGM) or use an insulin-dosing algorithm. Instead, the device delivers programmable basal insulin with ≤2 selectable basal rates and allows users to administer manual bolus doses. The hosts note its 300-unit insulin reservoir, highlighting the larger capacity as a potential advantage for individuals with higher daily insulin requirements. Bellini discusses where Pivot may fit into current clinical practice, suggesting it could provide an option for people who are unwilling or unable to use CGM technology but would still benefit from wearable insulin delivery. She also points to the possibility of future partnerships with commercially available AID algorithms, which could allow the platform to evolve into a more automated system. The hosts acknowledge that current diabetes guidelines generally favor AID for individuals with type 1 diabetes but recognize that simplified technologies continue to have an important role for select patient populations. The discussion expands to the broader pipeline of tubeless insulin pumps currently under development. Isaacs and Bellini review anticipated products from Tandem, Beta Bionics, and Medtronic, noting that virtually every major insulin pump manufacturer is now investing in patch pump technology. They compare reservoir capacities, expected timelines, and device designs while emphasizing the increasing demand for tubeless systems that improve convenience and reduce many of the practical challenges associated with traditional tubing. The hosts also examine several practical design considerations. They discuss Pivot's reusable and disposable components, explaining that many newer patch pumps incorporate reusable elements because of existing intellectual property surrounding fully disposable tubeless systems. While reusable components may lower manufacturing costs, they also introduce considerations such as the potential for patients to misplace components or inadvertently lose them during hospitalizations. Isaacs adds that the simplified design and absence of an onboard algorithm may ultimately make the device more affordable, although real-world pricing remains to be determined. Attention then shifts to recent updates from CeQur Simplicity, which recently announced a 7-day bolus-only patch featuring an expanded 240-unit insulin reservoir and a new one-unit dosing option for individuals requiring smaller mealtime insulin doses. The hosts discuss how these enhancements could broaden the device's applicability while maintaining its emphasis on simplicity, requiring neither smartphone connectivity nor a dedicated mobile application. Bellini highlights the potential synergy between the 7-day patch and emerging once-weekly basal insulin formulations, suggesting that synchronizing weekly basal insulin administration with weekly patch replacement could simplify treatment routines and improve adherence. She emphasizes that insulin therapy should continue to complement guideline-directed pharmacologic management, including GLP-1 receptor agonists, SGLT2 inhibitors, and other glucose-lowering therapies when appropriate. The episode concludes with an optimistic assessment of the future of insulin delivery technology. Isaacs and Bellini emphasize that increasing competition among manufacturers is likely to expand patient choice, improve affordability, and accelerate innovation. They express particular enthusiasm for the continued growth of tubeless insulin delivery, broader pharmacy benefit coverage, and the next generation of AID systems, all of which they believe will further individualize diabetes management and improve outcomes for people requiring insulin therapy. Editors’ Note: Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others. Bellini reports disclosures with Abbott Diabetes Care, MannKind, Povention Bio, and others.

    14min
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  5. Number 5: CONNECT, TRANSCEND, and TRIUMPH at ADA 2026

    Welcome back to Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives! In this episode, shot live at the American Diabetes Association (ADA) Scientific Sessions 2026 in New Orleans, Louisiana, cohosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss the latest major trial results like CONNECT, TRIUMPH, and TRANSCEND. To begin the episode, Isaacs and Bellini, discuss major highlights from ADA Scientific Sessions, focusing first on the landmark CONNECT trial evaluating continuous glucose monitoring (CGM) in people with type 2 diabetes who are not treated with insulin. They reflect on the evolution of CGM technology, from its early use primarily in type 1 diabetes to its expanding role in type 2 diabetes management, and explain why this trial represents an important step forward for patients who have historically had limited access to CGM. The hosts review the randomized controlled trial findings, emphasizing the significant improvements in glycemic outcomes, including a 1.6% reduction in A1c from baseline and an approximately 0.9% greater reduction compared with standard care. They also highlight the increase in time in range, with participants using CGM achieving roughly five additional hours per day in target glucose range. The magnitude of these findings is discussed as a practice-changing development, with the potential to influence future clinical guidelines and strengthen recommendations for CGM use among individuals with type 2 diabetes who are not using insulin. The discussion also explores the broader implications of the CONNECT trial for healthcare access and insurance coverage. The hosts note that randomized controlled trial evidence has historically played a key role in shaping standards of care and payer decisions, and they suggest that these results may help support wider adoption of CGM by demonstrating meaningful improvements in glucose control and patient outcomes. The conversation then shifts to emerging pharmacologic advances, with a focus on retatrutide, a novel triple agonist targeting GLP-1, GIP, and glucagon pathways. The hosts discuss new data showing substantial metabolic benefits in people with type 2 diabetes, including up to 17% weight reduction and nearly 2% A1c lowering. They highlight how these findings represent a major advancement in diabetes and obesity treatment, particularly as clinicians continue to see increasingly powerful effects from next-generation incretin-based therapies. Isaacs and Bellini explore how these therapies may reshape treatment strategies by allowing clinicians to tailor medication choices based on individual patient needs and goals. They discuss the importance of considering both glucose lowering and weight reduction effects, recognizing that some patients may benefit from significant weight loss while others may require a more balanced approach focused primarily on glycemic improvement. The hosts also address important unanswered questions surrounding the use of highly effective weight-loss medications, including appropriate treatment targets, the limitations of BMI as a measure, and the importance of preserving muscle mass and overall function. They emphasize the need to consider body composition, physical activity, resistance training, and patient characteristics—particularly in older adults or those at risk for frailty—when developing long-term treatment plans. The episode concludes with a reflection on the rapidly evolving landscape of diabetes care. The hosts highlight how advances in CGM technology and novel metabolic therapies are creating new opportunities to improve outcomes, personalize treatment approaches, and redefine the future management of people living with diabetes. Editors’ Note: Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others. Bellini reports disclosures with Abbott Diabetes Care, MannKind, Povention Bio, and others.

    14min
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