Diana Isaacs, PharmD, is an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic.

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES

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

Diabetes Dialogue: Celebrating 2025 as The Year of the Incretin Therapy

The rise of GLP-1 receptor agonists across a multitude of specialties and into the public consciousness has been meteoric and while many specialties now marvel at the effects of the class, endocrinology has been bearing witness to this ascent for years.

In 2025, several regulatory decisions and clinical trials have been nothing short of practice-changing, emphasizing the broad applicability of this medication across diabetes, obesity, chronic kidney disease, heart failure, and a variety of other conditions. Additionally, key approvals from the US Food and Drug Administration have positioned GLP-1 agents as critical components in the ongoing effort to lastingly and effectively treat obesity.

In this special edition of Diabetes Dialogue recorded for HCPLive’s 

, cohosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and co-director of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, review an unprecedented year of advances in incretin-based therapies in 2025.

Isaacs and Bellini open this episode by highlighting a landmark milestone from January 2025: the FDA’s approval of semaglutide for patients with type 2 diabetes and CKD, based on the FLOW trial. Bellini emphasizes how FLOW reshaped treatment algorithms by definitively establishing renal protection as a primary, not incidental, benefit of semaglutide. With clear evidence that GLP-1 receptor agonists can slow progression to advanced CKD—even when SGLT2 inhibitors are not tolerated—the hosts note this represents a genuine paradigm shift toward confident combination therapy.

February: FDA Ends the Semaglutide Shortage

Isaacs and Bellini also highlighted the end of the global semaglutide shortage in February 2025. During the shortage, clinicians were often forced to switch patients between multiple medications to achieve similar treatment with a limited supply. Oftentimes, as Bellini notes, patients using a 2 mg dose were moved to 1 mg when the former ran out, and then to an 0.5 mg dose when the 1 mg dose ran out. Novo Nordisk’s ultimate decision to ramp up production of semaglutide significantly alleviated the pressures of the shortage, and since then, the field has seen a substantial decrease in usage of compounding pharmacies.

March: STRIDE and Semaglutide in Peripheral Artery Disease

Conversation turns to March and the STRIDE trial, where semaglutide significantly improved pain-free walking distance in patients with peripheral artery disease. Isaacs and Bellini underscore how this data reinforces GLP-1 agents as cardiometabolic therapies with broad vascular relevance, particularly given the accessibility of walking as a functional endpoint. Additionally, the trial highlighted the cardiovascular aspect of diabetes, as it substantially increases heart attack and stroke risk – making diabetes the ideal crosspoint for adopting GLP-1 agents into cardiovascular care.

June: The American Diabetes Association Scientific Sessions

June’s ADA Scientific Sessions brought an “explosive” volume of incretin data. They spotlight the monthly GLP-1 candidate MariTide, producing ~16% weight loss in early studies; the oral GLP-1 orforglipron, which delivered strong A1c and weight reductions without dosing-timing constraints; and the dual amylin/GLP-1 combination Cagri-Sema (semaglutide and cagrilintide) in the REDEFINE program, with weight-loss results surpassing 20% in people without diabetes and nearly 14% in those with type 2 diabetes. They also discuss STEP UP, where a higher 7.2-mg semaglutide dose achieved a 21% weight reduction with acceptable tolerability, and the SLIMMER trial’s glucagon/GLP-1 dual-agonist ecnoglutide, which delivered more than 13% mean weight loss. The hosts emphasize that, taken together, these studies signal a future defined by combination incretin pharmacology and diversified receptor targeting.

July: SURPASS-CVOT and Tirzepatide in Cardiovascular Disease

The July discussion centers on the SURPASS-CVOT top-line results. Although tirzepatide did not demonstrate superiority over dulaglutide, it achieved cardiovascular noninferiority, reinforcing clinical comfort in using tirzepatide for patients with elevated CV risk. They highlight the pre-specified indirect comparison suggesting a potential 28% reduction in three-point MACE and 39% reduction in all-cause mortality relative to a putative placebo. Additional analyses indicating slowed eGFR decline in high-risk CKD populations further broaden the therapeutic rationale.

August: Semaglutide in MASH and Orforglipron in Obesity

August delivered another milestone with semaglutide gaining FDA approval for metabolic dysfunction–associated steatohepatitis (MASH), becoming only the second therapy approved for this increasingly recognized condition. The hosts describe how this approval is already changing clinical workflows—with broader screening, routine incorporation of FIB-4 scoring, and stronger justification for GLP-1–based therapy in metabolic liver disease. In parallel, orforglipron produced 12% weight loss in obesity trials, signaling likely future broad utility.

By October, oral semaglutide achieved its own cardiovascular-risk-reduction indication via the SOUL trial, alleviating long-standing concerns about the CV efficacy of oral formulations. This new data also opened a new potential treatment pathway for patients unwilling or unable to receive injectable agents. Semaglutide is now the only oral GLP-1 receptor agonist currently available, but the promising results of SOUL promise more to come.

November: Semaglutide in Alzheimer’s Disease

Isaacs and Bellini review November’s disappointing termination of Novo Nordisk’s oral semaglutide Alzheimer’s disease trial, in which the GLP-1 agent was unable to prevent disease progression to a statistically significant degree. While progression was not slowed, the hosts point to expert commentary suggesting the possibility that therapy must begin earlier or use injectable formulations to meaningfully influence neurodegenerative pathways, leaving the door open for future investigation.

December: SURMOUNT-4 and Weight Gain After Withdrawal from Tirzepatide

The episode concludes with new post-hoc findings from SURMOUNT-4, showing that more than 80% of individuals withdrawing from tirzepatide regained at least 25% of their prior weight loss, accompanied by reversal of cardiometabolic improvements. Isaacs and Bellini stress the core message: obesity is a chronic disease requiring chronic treatment, and the accumulating benefits of incretin-based therapies—in renal protection, cardiovascular risk reduction, liver disease, and weight management—reinforce the importance of long-term continuity.

Novo Nordisk. FDA approves Ozempic® (semaglutide) as the only GLP-1 RA to reduce the risk of worsening kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. January 28, 2025. Accessed January 28, 2025. 

https://www.novonordisk-us.com/media/news-archive/news-details.html?id=915253

Novo Nordisk. FDA declares Wegovy® and Ozempic® shortage is over and that Novo Nordisk is fully meeting or exceeding nationwide demand for all doses. PR Newswire: press release distribution, targeting, monitoring and marketing. February 21, 2025. Accessed February 21, 2025. 

https://www.prnewswire.com/news-releases/fda-declares-wegovy-and-ozempic-shortage-is-over-and-that-novo-nordisk-is-fully-meeting-or-exceeding-nationwide-demand-for-all-doses-302382370.html

Bonaca MP, Catarig A, Houlind K. Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial. 

Johnson V. ADA 2025 Recap: 5 Studies on Obesity to Know. Hcplive.com. Published June 25, 2025. Accessed December 3, 2025. 

https://www.hcplive.com/view/ada-2025-recap-5-studies-on-obesity-to-know

Eli Lilly and Company. Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist, demonstrated cardiovascular protection in landmark head-to-head trial, reinforcing its benefit in patients with type 2 diabetes and heart disease. July 31, 2025. Accessed July 31, 2025. 

https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated

Novo Nordisk. Wegovy® approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. August 15, 2025. Accessed August 15, 2025. 

https://www.novonordisk-us.com/media/news-archive/news-details.html?id=916417

Eli Lilly and Company. Lilly's oral GLP-1, orforglipron, delivers weight loss of up to an average of 27.3 lbs in first of two pivotal Phase 3 trials in adults with obesity. August 7, 2025. Accessed August 7, 2025. 

https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-delivers-weight-loss-average-273

Novo Nordisk, Inc. FDA approves Novo Nordisk’s oral semaglutide for cardiovascular (CV) risk reduction in adults with type 2 diabetes who are at high risk, including those who have not had a prior CV event. PR Newswire. October 17, 2025. Accessed October 20, 2025. 

https://www.prnewswire.com/news-releases/fda-approves-novo-nordisks-oral-semaglutide-for-cardiovascular-cv-risk-reduction-in-adults-with-type-2-diabetes-who-are-at-high-risk-including-those-who-have-not-had-a-prior-cv-event-302588005.html

Novo Nordisk. Novo Nordisk A/S: Evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer’s disease progression. November 24, 2025. Accessed November 24, 2025. 

https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916462

Horn DB, Linetzky B, Davies MJ, et al. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial. 

 Published online November 24, 2025. doi:10.1001/jamainternmed.2025.6112

Podcasts

This special edition episode explores the advancements in incretin therapies that defined 2025.

Diabetes Dialogue hosts discuss November 2025 technology updates, including Omnipod updates from Insulet Corporation

Diabetes Dialogue: Upcoming Upgrades for Omnipod Technology

In this episode of Diabetes Dialogue, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and co-director of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, break down what Insulet Corporation’s announcements surrounding forthcoming updates to Omnipod mean for the diabetes community.

At its 2025 Innovation Showcase, Insulet Corporation highlighted a series of major product advancements that are expected to significantly expand the clinical utility of automated insulin delivery (AID) for both type 1 and 

. The company outlined 3 sequential product launches between 2026 and 2028, each designed to simplify therapy, enhance glycemic outcomes, and broaden access to AID across diverse clinical settings.

Pending FDA clearance, Insulet plans upgrades to the current Omnipod 5 system, which became the first FDA-approved AID system for type 2 diabetes in August 2024,  to strengthen glycemic control, improve usability, and expand ecosystem connectivity. Key clinical-facing improvements include:

Full interoperability with all major continuous glucose monitoring (CGM) systems.

Improved algorithmic performance designed to optimize time-in-range and reduce hypoglycemia.

Omnipod Discover, a new machine-learning insights platform, intended to streamline onboarding, simplify dose adjustment, and support clinical decision-making with real-time, data-driven recommendations.

Insulet’s next AID platform, Omnipod 6, introduces a redesigned system built to elevate both personalization and simplicity:

An adaptive insulin-dosing algorithm that continuously learns and adjusts to each user’s glucose patterns.

A configurable Pod engineered to function with 

A new app and controller interface emphasizing intuitive setup, patient autonomy, and reduced clinic training burden.

Omnipod 6 is intended for use in both type 1 and type 2 diabetes, expanding AID applicability to the large population of insulin-requiring type 2 patients who have had limited access to pump therapy.

Omnipod Fully Closed Loop for Type 2 Diabetes (Expected 2028)

Insulet also announced plans for the Omnipod Fully Closed Loop for Type 2, which is designed as the first out-of-the-box, fully automated insulin delivery system for type 2 diabetes:

No meal announcements, carb counting, or manual boluses required

An intelligent algorithm that autonomously manages basal and bolus insulin delivery

Zero-setup design intended to enable prescription and use in primary care, dramatically broadening AID access

Relevant disclosures for Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

Insulet Corporation. Insulet Outlines Long-Term Strategy to Drive Growth and Value Creation at 2025 Investor Day. Insulet.com. Published November 20, 2025. Accessed November 25, 2025. 

https://investors.insulet.com/news/news-details/2025/Insulet-Outlines-Long-Term-Strategy-to-Drive-Growth-and-Value-Creation-at-2025-Investor-Day/default.aspx

Insulet Corporation. Omnipod® 5 Automated Insulin Delivery System is now FDA-cleared for People with Type 2 Diabetes. Insulet.com. Published August 26, 2024. Accessed November 25, 2025. 

https://investors.insulet.com/news/news-details/2024/Omnipod-5-Automated-Insulin-Delivery-System-is-now-FDA-cleared-for-People-with-Type-2-Diabetes/default.aspx

Discover the latest advancements in diabetes technology from November 2025, including Omnipod updates and the new Pivot pump.

In this episode of Diabetes Dialogue, hosts discuss Semaglutide for Alzheimer Disease and new trial data on Tirzepatide showing promise in T1D

Diabetes Dialogue: Semaglutide Falls Short Alzheimer Disease, Tirzepatide Shows Promise in T1D

In this episode, hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, breakdown recent trial news from the 2 most popular incretin therapies: semaglutide and tirzepatide. First, hosts breakdown the November 24, 2025 announcement from Novo Nordisk disclosing their evoke and evoke+ trials of oral semaglutide in early symptomatic 

 failed to slow disease progression. Next, hosts break down the TIRTLE study, which examined use of tirzepatide in patients with 

Semaglutide Misses Mark in Alzheimer Disease

Novo Nordisk announced top-line results from the evoke and evoke+ phase 3 trials showing oral semaglutide 14 mg did 

 slow disease progression over 2 years in adults with early symptomatic Alzheimerdisease, with no significant difference in CDR-SB change versus placebo. Despite improvements in Alzheimer-related biomarkers across both studies, neither trial demonstrated a slowing of clinical decline.

evoke was a global, randomized, double-blind, placebo-controlled trial enrolling 1,855 participants aged 55–85 with amyloid-positive CDR 0.5 MCI or CDR 1.0 mild dementia, treated 1:1 with semaglutide or placebo for 104 weeks plus a planned 52-week extension. evoke+ mirrored this design, randomizing 1,953 participants with the same eligibility criteria to daily semaglutide 14 mg or placebo for a total planned duration of 156 weeks.

Findings from the trials will be presented at the 2025 Clinical Trials in Alzheimer’s Disease (CTAD) conference on December 3, 2025. The lack of efficacy led to discontinuation of the planned 1-year extension period across both trials, though safety and tolerability remained consistent with prior semaglutide experience in diabetes and obesity.

TIRTLE: Tirzepatide Shows Benefit in Type 1 Diabetes

In a 12-week, double-blind, placebo-controlled phase 2 trial of 24 adults with type 1 diabetes and BMI >30 kg/m², tirzepatide produced a 10.3-kg mean weight loss versus 0.7 kg on placebo, an −8.7-kg treatment difference (

 < 0.0001) corresponding to 8.8% total body weight reduction.

All tirzepatide-treated participants achieved ≥5% weight loss, and 45% achieved ≥10%, compared with 9% and 0% in the placebo group. Eligibility criteria required patients to be 18 years of age or older, with confirmed type 1 diabetes, obesity (BMI >30), and stable insulin therapy. Tirzepatide also improved glycemic control, reducing HbA1c by 0.4%, and decreased total daily insulin dose by 35% relative to placebo (−24.2 vs −0.3 units/day). Safety data suggested no significant adverse events occurred, with 22 of the 24 participants completing the study.

Novo Nordisk. Novo Nordisk A/S: Evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer’s disease progression. Novo Nordisk. November 24, 2025. Accessed November 24, 2025. 

Snaith JR, Frampton R, Samocha-Bonet D, Greenfield JR. Tirzepatide in Adults With Type 1 Diabetes: A Phase 2 Randomized Placebo-Controlled Clinical Trial. 

. Published online November 20, 2025. doi:

Explore the latest findings on GLP-1 drugs, including their impact on Alzheimer's and promising results for type 1 diabetes treatment.

Diabetes Dialogue: Semaglutide Falls Short in Alzheimer Disease, Tirzepatide Shows Promise in T1D

Diabetes Dialogue: Updates on Dexcom G7 and Semaglutide Pricing

In this episode of Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and co-director of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, review two major developments in diabetes care: the forthcoming 15-day Dexcom G7 continuous glucose monitor (CGM) and significant new price reductions for semaglutide across Ozempic and Wegovy.

00:00:01 Introduction
00:00:30 Dexcom G7
00:01:55 A 15-Day Sensor With a 12-Hour Grace Period
00:04:27 Seamless transition to the new G7
00:05:23 Looking back at Dexcom's advancements
00:06:34 Dexcom's Smart Basal feature
00:10:34 Price cuts for semaglutide - Wegovy and Ozempic
00:14:54 Cheaper GLP-1s on the pharmacies' end
00:20:33 Outro

Isaacs and Bellini first outline Dexcom’s announcement that the 15-day G7 sensor will launch on December 1 through durable medical equipment channels, with pharmacy availability to follow shortly afterward. The extended-wear sensor maintains the same form factor, app platform, and accuracy profile users expect, now with a 15.5-day life enabled by a built-in 12-hour grace period. Integration with Omnipod 5 and iLet will be available at launch, with Control-IQ+ compatibility expected later. Both hosts emphasize how reduced sensor-change burden and seamless pump integration can streamline therapy, particularly as CGM adoption accelerates in primary care and among people with 

. They note, however, that the initial FDA clearance is limited to adults 18 and older, with pediatric expansion expected as post-market data develop.

The hosts also highlight advances in data-sharing and the newly cleared Smart Basal feature within the G7 15-day app experience. This tool uses CGM-driven analytics to support clinicians and patients in basal insulin titration, particularly for glargine. The system adjusts doses based on comprehensive glycemic patterns rather than isolated fasting values, incorporates customizable hypoglycemia safeguards, and identifies a final “optimal dose” once glucose stabilizes. Isaacs and Bellini underscore the potential impact for primary care, where under-titration of basal insulin is common and follow-up intervals can be lengthy.

The conversation then shifts to sweeping pricing updates for semaglutide. New self-pay pricing allows patients to access Ozempic for $199 for the first two months and $349 thereafter—a steep reduction from previous cash prices. Wegovy pricing aligns similarly across all doses. While acknowledging that affordability remains a challenge for many, the hosts view this as a substantial improvement, bringing U.S. pricing closer to international norms and potentially expanding access for individuals who fall between traditional insurance coverage and patient-assistance eligibility. They also note updated criteria for assistance programs, ongoing availability of copay cards, and similar price reductions for tirzepatide’s Zepbound starter dose. Practical considerations for pharmacies, insurance dynamics, and cash-pay logistics are discussed, with the hosts optimistic about simplified access and broader uptake.

They conclude by emphasizing how these advances - longer-wear CGM technology, AI-supported insulin titration, and more accessible incretin-based therapies - collectively strengthen the future of diabetes management and expand opportunities for improved outcomes across clinical settings.

This episode covers the upcoming release of Dexcom's G7 15-day patch and major price cuts for semaglutide.

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES

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