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

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

Diabetes Dialogue: Oral GLP-1 Orforglipron in ACHIEVE-1 Trial

00:00:01 Discussion on OR for GLP-1 Receptor Agonist

00:02:13 Potential Impact and Patient Preferences

00:08:55 Cardiovascular Outcome Data and Conclusion

In this episode of Diabetes Dialogue, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, discuss the top-line results from the ACHIEVE-1 trial evaluating orforglipron—an investigational, once-daily oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) developed by Eli Lilly—for adults with 

 inadequately controlled by diet and exercise.

Isaacs and Bellini emphasized the clinical significance of orforglipron’s Phase 3 data in the ACHIEVE-1 trial, which demonstrated substantial reductions in A1c (1.3–1.6%) from a baseline of 8.0% and notable weight loss averaging 16 pounds (7.9%) at the highest dose over 40 weeks. Impressively, more than 65% of participants achieved an A1c below 6.5%, meeting the American Diabetes Association (ADA)’s target for diabetes control.

The hosts highlighted the convenience advantage of orforglipron compared to oral semaglutide, which has strict dosing requirements. Oral orforglipron can be taken without food or water restrictions, potentially increasing adherence and reducing treatment burden. They also noted the drug’s favorable safety profile, with gastrointestinal side effects similar in type and incidence to existing GLP-1 RAs, and no hepatic safety signals observed in the trial.

Beyond glycemic control, Isaacs and Bellini discussed the broader implications for obesity treatment, pointing to the drug’s potential utility in weight management, pending regulatory submission. They explored the possibility of using injectable GLP-1 RAs for initial weight loss followed by oral maintenance with orforglipron—potentially lowering costs and improving access.

The conversation touched on the upcoming ACHIEVE trial series, which will explore orforglipron in head-to-head comparisons with other agents, its use in insulin-treated T2D, and future indications including cardiovascular risk and kidney disease.

While optimistic, the hosts stressed the need for cardiovascular outcomes data to confirm orforglipron’s safety and potential benefits in this domain. If confirmed, they suggested orforglipron could become a cornerstone oral therapy for T2D and obesity.

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.

Lilly’s oral GLP-1, Orforglipron, demonstrated statistically significant efficacy results and a safety profile consistent with injectable GLP-1 medicines in successful phase 3 trial. Eli Lilly and Company. April 17, 2025. Accessed April 17, 2025. 

https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-demonstrated-statistically

Lilly’s Phase 2 results published in the New England Journal of Medicine Show Orforglipron, a once-daily oral nonpeptide GLP-1 receptor agonist, achieved up to 14.7% mean weight reduction at 36 weeks in adults with obesity or overweight. Press Release Archive. June 23, 2025. Accessed April 23, 2025. 

https://lilly.mediaroom.com/2023-06-23-Lillys-phase-2-results-published-in-the-New-England-Journal-of-Medicine-show-orforglipron,-a-once-daily-oral-nonpeptide-GLP-1-receptor-agonist,-achieved-up-to-14-7-mean-weight-reduction-at-36-weeks-in-adults-with-obesity-or-overweight

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In this episode, hosts explore promising results of orforglipron, a new oral GLP-1 receptor agonist, showing significant A1C reduction and weight loss potential.

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

Diabetes Dialogue: SCORE, Semaglutide, and ACC Wrap-up

In this episode, 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 a pair of studies examining the effects of semaglutide and long-acting GLP-1 receptor agonists (GLP-1 RAs).

Real-World Semaglutide Effects from SCORE Study

Building on the SELECT trial, which demonstrated semaglutide 2.4 mg (Wegovy) significantly reduced cardiovascular risk in people with 

atherosclerotic cardiovascular disease (ASCVD)

 and obesity but without diabetes, the new SCORE study provides real-world validation of these benefits in a US population.

Using claims and EMR data, researchers matched 9321 semaglutide 2.4 mg users with 18,642 non-users, all aged 45 years or older, with ASCVD and overweight or obesity but no diabetes. The groups were balanced using a propensity score matching method.

The analysis showed that semaglutide 2.4 mg use was associated with a 46% lower risk of 5-point major adverse cardiovascular events (MACE)—which includes myocardial infarction, stroke, hospitalization for heart failure, coronary revascularization, and all-cause death (HR, 0.54; 95% CI, 0.43 to 0.69; 

 <.001). The risk of all-cause death alone was reduced by 87% in semaglutide users compared to non-users (HR, 0.13; 95% CI, 0.06 to 0.28; 

Meta-analysis of Randomized Trials for GLP-1s in T2D

A new meta-analysis, including recently published data from the SOUL and FLOW trials, reinforces the cardiovascular and kidney benefits of long-acting GLP-1 Res in individuals with 

Across 10 large, placebo-controlled trials containing 71,351 individuals, long-acting GLP-1RAs were associated with a 14% reduction in MACE (HR, 0.86; 95% CI, 0.81 to 0.90; I² = 27.6%), a 14% reduction in hospitalization for heart failure (HR, 0.86; 95% CI, 0.79 to 0.93; I² = 2.1%), and a 17% reduction in a composite kidney outcome (HR, 0.83; 95% CI, 0.75 to 0.92; I² = 20.4%). All-cause mortality was reduced by 12% (HR, 0.88; 95% CI, 0.82 to 0.93; I² = 17.5%), and each individual MACE component—cardiovascular death, myocardial infarction, and stroke—showed a consistent 14% risk reduction.

Benefits were consistent regardless of administration route, and no increased risks were observed for severe hypoglycemia, retinopathy, or pancreatic events.

Zhao Z, Song J, Faurby M, et al. LOWER RISK OF MACE AND ALL-CAUSE DEATH IN PATIENTS INITIATED ON SEMAGLUTIDE 2.4 MG IN ROUTINE CLINICAL CARE: RESULTS FROM THE SCORE STUDY (SEMAGLUTIDE EFFECTS ON CARDIOVASCULAR OUTCOMES IN PEOPLE WITH OVERWEIGHT OR OBESITY IN THE REAL WORLD). Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

Lee MMY, Sattar N, Pop-Busui R, et al. Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials. 

This episode spotlights a pair of studies examining use of semaglutide from the American College of Cardiology's 2025 Scientific Sessions.

Diabetes Dialogue: Screening for Presymptomatic T1D with Rifka Schulman-Rosenbaum, MD

00:04:12 Challenges in Implementing T1D Screening

00:07:32 Educating Providers and Overcoming Barriers

00:09:32 Addressing Misdiagnosis of Diabetes

00:16:13 Support and Resources for Patients with Positive Antibodies

In this episode of Diabetes Dialogue, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, are joined by Rifka Schulman-Rosenbaum, MD, director of inpatient diabetes at Long Island Jewish Medical Center and co-author of Establishing Screening Programs for Pre-symptomatic Type 1 Diabetes: Practical Guidance for Diabetes Care Providers, a new paper in the Journal of Clinical Endocrinology and Metabolism.

With Bellini as a co-author of the piece, experts explored the increasing clinical and operational momentum behind screening for 

 and what it takes to implement effective programs in real-world settings.

The conversation centers on the rationale and logistics behind identifying individuals in stages 1 and 2 of T1D—autoimmune stages characterized by multiple islet autoantibodies before clinical onset. With the availability of teplizumab (Tzield), a disease-modifying therapy shown to delay progression to stage 3 of T1D, the importance of early detection and standardized screening protocols has become more urgent.

Schulman-Rosenbaum outlined how her work on the JDRF Breakthrough T1D initiative led to the development of actionable guidance aimed at frontline diabetes care providers. She highlights barriers to implementation—such as limited provider awareness of T1D staging and screening protocols—and details her institution’s ongoing efforts to educate primary care clinicians and endocrinologists, including distributing screening handouts and creating streamlined workflows using dot phrases and dedicated follow-up slots.

The discussion emphasizes targeted screening for high-risk groups, such as first- and second-degree relatives of individuals with T1D and patients with autoimmune diseases like Hashimoto’s or celiac. Schulman-Rosenbaum emphasized the opportunity for endocrinologists to screen these patients directly during routine care and the utility of a centralized handout to guide test ordering and family engagement.

Drawing from their paper, experts outlined practical steps for launching autoantibody screening programs: nominating a program champion, forming an implementation team, and embedding screening into existing clinical systems. Experts stressed the importance of using appropriate ICD-10 codes for insurance coverage and referenced a diagnostic coding table in their publication.

Schulman-Rosenbaum also addressed the widespread issue of misdiagnosis, particularly in adults mistakenly classified as having type 2 diabetes, and outlines best practices for using antibody and C-peptide testing to refine diagnosis. She detailed her hospital’s approach to inpatient screening, noting an increased use of autoantibody testing and follow-up coordination for patients with suspected T1D or latent autoimmune diabetes in adults (LADA).

Finally, the episode highlighted how to monitor individuals who test positive for a single antibody or exhibit mild dysglycemia, noting that many fall outside established risk categories. Experts called for more research in this area and advocate for individualized monitoring strategies based on clinical risk, family history, and emerging glucose patterns—often using continuous glucose monitoring (CGM) data.

Leichter SB, Felton JL, Rasmussen CG, et al. Establishing Screening Programs for Presymptomatic Type 1 Diabetes: Practical Guidance for Diabetes Care Providers. 

. Published online April 2, 2025. doi:10.1210/clinem/dgaf194

In this episode, experts discuss practical guidance for screening for presymptomatic type 1 diabetes with Rifka Schulman-Rosenbaum, MD.

Diabetes Dialogue: STRIDE and SOUL Trials at ACC 2025

In this episode, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, explored two key trial updates in type 2 diabetes (T2D) care at the 

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

SOUL, a double-blind, placebo-controlled, event-driven trial, was designed to assess the cardiovascular effects of oral semaglutide (Rybelsus) in patients with T2D and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). A total of 9650 patients aged ≥50 years were enrolled across 450 centers in 44 countries.

Analyses showed oral semaglutide (Rybelsus) was linked to a 14% reduction in major adverse cardiovascular events (MACE) in high-risk patients with T2D. This reduction included the incidence of cardiovascular (CV) death, myocardial infarction (MI), or stroke compared to placebo (HR, 0.86; 95% CI, 0.77 to 0.96; P = .006) over a median follow-up of 47.5 months.

A 26% reduction in non-fatal MI was the primary driver of benefit, while safety findings identified gastrointestinal adverse events as more common with oral semaglutide. Based on these results, Novo Nordisk announced plans to pursue regulatory approval for a label expansion of oral semaglutide to include MACE risk reduction in adults with T2D and established CV disease.

STRIDE, a double-blind, randomized, placebo-controlled trial initiated in 2020, assessed the effects of semaglutide 1.0 mg (Ozempic) on functional outcomes, including walking distance, in patients with T2D and peripheral artery disease (PAD). Conducted across 112 sites in 20 countries, the trial randomized 792 patients to receive semaglutide or placebo for 52 weeks.

Analyses showed semaglutide use was associated with improvements in maximal walking distance, quality of life, and ankle-brachial index (ABI). SOUL met its primary endpoint, with semaglutide favoring the ratio from baseline in maximum walking distance at 52 weeks (1.21 [interquartile range, 0.95–1.55] vs 1.08 [0.86–1.36]), with an estimated treatment ratio (ETR) of 1.13 (95% CI, 1.06–1.21; 

At week 57, the improvement in walking distance was higher with semaglutide (ETR, 1.08; 

 = .038). Quality-of-life scores (VascuQoL-6) at week 52 were significantly higher in the semaglutide group (median difference, 1.00; 

 = .011), as were improvements in pain-free walking distance (ETR, 1.11; 

: In this episode, there was an error in the discussion about the new dosing for Rybelsus in the SOUL trial. The corrected information is that the 14 mg dose is now 9 mg with the new formulation, due to improved absorption. The full corrected statement is: “Instead of 3 mg, the new dose is 1.5 mg; instead of 7 mg, it’s 4 mg; and instead of 14 mg, it’s 9 mg.”

In this episode, hosts break down the STRIDE and SOUL trials presented at the American College of Cardiology 2025 Annual Scientific Sessions.

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

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