Natalie Bellini, DNP, FNP-BC, BC-ADM, CDCE

Diabetes Dialogue: 2024 ACP Type 2 Recommendations

A reflection of the growing evidence base supporting the safety and efficacy of these classes in management of 

 and related comorbidities, the American College of Physicians has released new recommendations in favor of SGLT2 inhibitors and GLP-1 receptor agonists and against use of DPP-4 inhibitors as second-line therapies to metformin in adults with type 2 diabetes and inadequate glycemic control.

“As additional pharmacological treatments become available for the treatment of Type 2 diabetes, it’s critical for us to examine their effectiveness, the harms and benefits as well as costs in order to provide the best treatment for our patients,” said Carolyn J. Crandall, MD, MS, an internal medicine physician at the University of California Los Angeles School of Medicine and the chair of the Guidelines Committee.

, the pair of recommendations reflect the findings from a systematic review and network meta-analysis and cost-effectiveness analysis assessing the value of these therapies as both monotherapies and in combination with metformin. Of note, the recommendations do not consider the effects of each class on glycemic parameters.

The recommendations from the ACP are as follows:

Recommendation 1: Add an SGLT2 inhibitor or GLP-1 receptor agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence).

Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.

Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.

Recommendation 2: Against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

Attendees at this year’s Internal Medicine Meeting, 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 ACP’s latest recommendations in a special ACP 2024 edition of 

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

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

Qaseem A, Obley AJ, Shamliyan T, Hicks LA, Harrod CS, Crandall CJ. Newer pharmacologic treatments in adults with type 2 diabetes: A clinical guideline from the American College of Physicians. 

. Published online April 19, 2024. doi:10.7326/m23-2788

American College of Physicians. ACP issues clinical recommendations for newer pharmacological treatments of adults with type 2 diabetes. ACP issues clinical recommendations for newer pharmacological treatments of adults with Type 2 diabetes | ACP Online. April 19, 2024. Accessed April 19, 2024. https://www.acponline.org/acp-newsroom/acp-issues-clinical-recommendations-for-newer-pharmacological-treatments-of-adults-with-type-2.

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In this episode, hosts break down the latest type 2 diabetes recommendations from the American College of Physicians and offer their perspective on second-line therapies in T2D.

Diabetes Dialogue: 2024 ACP Type 2 Diabetes Recommendations

Discussion on the STEP HFpEF DM trial and the need for fair allocation of incretin-based therapies with ongoing shortages and overwhelming demand.

Diabetes Dialogue: STEP HFpEF DM and Fair Allocation of Incretin-Based Therapies

 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, tackle a pair of related topics: what the STEP HFpEF DM trial from ACC.24 means for the diabetes community and the need for fair and equitable allocation of incretin-based therapies in the face of ongoing drug shortages and overwhelming demand.

Presented at ACC.24 and simultaneously published in the 

STEP HFpEF DM was a randomized, double-blind, placebo-controlled trial that randomized 616 participants in a 1:1 ratio to semaglutide 2.4 mg or placebo therapy for 52 weeks. Conducted across 108 sites in 16 countries across Asia, Europe, and North and South America, inclusion criteria for the study required patients to have a left ventricular ejection fraction of 45% or greater, a BMI of 30 kg/m2 or greater, and type 2 diabetes.

Like the original STEP HFpEF trial, STEP HFpEF DM had dual primary endpoints, which were change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and change in body weight. STEP HFpEF DM also included multiple secondary confirmatory endpoints, these included change in 6-minute walk distance, a hierarchical composite end point of death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance, and the change in the C-reactive protein (CRP) level.

Results of the trial indicated use of semaglutide 2.4 mg was associated with a mean change from baseline KCCQ-CSS of 13.7 points compared to a 6.4-point change with placebo therapy (Estimated treatment difference [ETD], 7.3 points; 95% CI, 4.1 to 10.4; 

< .001). Analysis of body weight suggested the mean change from baseline was −9.8% with semaglutide 2.4 mg and −3.4% with placebo therapy (ETD, −6.4 percentage points; 95% CI, −7.6 to −5.2; 

< .001). Further analysis indicated pointed to benefit withsemaglutide 2.4 mg over placebo therapy for change in 6-minute walk distance (estimated between-group difference, 14.3 meters; 95% CI, 3.7 to 24.9; 

= .008), the hierarchical composite endpoint (win ratio, 1.58; 95% CI, 1.29 to 1.94; 

 < .001), and change in CRP level (estimated treatment ratio, 0.67; 95% CI, 0.55 to 0.80; 

Fair and Equitable Allocation of Incretin-Based Therapies

 an editorial penned by a group of 5 from the Department of Medical Ethics and Health Policy at the Perelman School of Medicine of the University of Pennsylvania and the Bergen Center for Ethics and Priority Setting at the University of Bergen brought forth ethical perspectives on the fair allocation of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists in the face of overwhelming demand and changing coverage of these agents.

In their editorial, the group proposes a 4-tiered system for allocation based on objectives of care and specified distribution criteria. In hierarchical order, these objectives are: to minimize potential years of life lost, prevent imminent medical complications, prevent future medical complications, and improve quality of life. In their discussion, Isaacs and Bellini discuss their real-world experience in balancing this issue as new data and indications continue to emerge.

Campbell P. Step HFPEF DM: Semaglutide 2.4 mg improves functional status, symptoms in patients with diabetes, HFPEF. HCP Live. April 6, 2024. Accessed April 17, 2024. https://www.hcplive.com/view/step-hfpef-dm-semaglutide-2-4-mg-improves-functional-status-symptoms-in-patients-with-diabetes-hfpef.

Emanuel EJ, Dellgren JL, McCoy MS, Persad G. Fair Allocation of GLP-1 and Dual GLP-1–GIP Receptor Agonists. 

. Published online April 17, 2024. doi:10.1056/NEJMp2400978

In this episode, hosts discuss the STEP HFpEF DM trial and the need for fair allocation of incretin-based therapies with ongoing shortages and overwhelming demand.

Hosts talk with Sequel Med Tech co-founder Alan Lotvin, MD, about the twiist AID system.

Diabetes Dialogue: What to Know about Sequel Med Tech's twiist AID System

The diabetes community welcomed an additional tool to the armamentarium with the US Food and Drug Administration’s clearance of the twiist automated insulin delivery (AID) system on March 18, 2024.

Cleared for use in patients aged 6 years and older with 

, the twiist, which is marketed by Sequel Med Tech, is billed as the first drug delivery system that directly measures volume and flow of inulin delivered with every micro-dose. Leveraging the Tidepool Loop algorithm, which enables the system to automatically adjust insulin delivery based on CGM readings and predicted glucose levels, the AID system was designed by Dean Kamen, the inventor of the world’s first wearable infusion insulin pump, with the intent of broadening patient choice and providing the most precise insulin delivery system to date, according to a press release from Sequel Med Tech.

“The clearance of the twiist AID system is a pivotal first step in Sequel’s quest to make day-to-day life easier for people with type 1 diabetes. The twiist system combines drug delivery technology that directly and precisely measures each dose of insulin, providing the opportunity for better control and flexibility,” said Alan Lotvin, MD, chief executive officer and co-founder Sequel Med Tech.

 “Sequel is working to simplify living with diabetes by introducing product and process innovation while expanding access for all."

 Lotvin joins 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, for a deep dive into the latest AID to receive approval, including the pump’s patient-centric design, why they chose to leverage the Tidepool Loop algorithm, plans for device launch, and more.

Sequel Med Tech. Sequel’s twiistTM automated insulin delivery system receives FDA 510(k) clearance. GlobeNewswire News Room. March 18, 2024. Accessed March 30, 2024. https://www.globenewswire.com/news-release/2024/03/18/2847675/0/en/Sequel-s-twiist-Automated-Insulin-Delivery-System-Receives-FDA-510-k-Clearance.html.

Campbell P. Tidepool loop mobile app receives FDA Marketing Clearance. HCP Live. January 26, 2023. Accessed March 30, 2024. https://www.hcplive.com/view/tidepool-loop-mobile-app-receives-fda-marketing-clearance.

In this episode, Alan Lotvin, MD, of Sequel Med Tech, joins hosts for a deep dive into the twiist automated insulin delivery system, which received clearance for people with T1D in March 2024.

Diabetes Dialogue: What to Know about Sequel Med Tech's twiist AID System, with Alan Lotvin, MD

In the third and final recap episode from ATTD 2024, hosts discuss a bevy of topics and updates from across diabetes management.

Diabetes Dialogue: Hot Topics and Updates from ATTD 2024

In the third and final recap episode from the 17th annual International Conference on Advanced Technologies & Treatments for Diabetes, hosts of 

 Diana Isaacs, PharmD, and Natalie Bellini, DNP, take a deep dive into a series of topics from the meeting, including GLP-1 receptor agonist use and CGM technology, updates in once-weekly insulins, the concept of continuous ketone monitoring, and application of artificial intelligence into care.

For more on ATTD 2024, check out our other ATTD 2024 episodes on 

T1D Glycemic Improvement and the CRISTAL Study

The first topic of interest for the episode was data Abbott detailing the effects of GLP-1 receptor agonist use alone and in conjunction with CGM technology. At the meeting, Abbott presented data from a real-world study examining the effect of a first FreeStyle Libre acquisition among 1781 patients with type 2 diabetes identified using Optum’s deidentified Market Clarity Data. This cohort had a mean age of age 55±10 years, 52% were male,the mean 499 days from GLP-1 initiation to FreeStyle Libre. Investigators pointed out the cohort had a baseline HbA1c of 9.8±1.5% and 38% used bolus insulin therapy.

Results indicated people with type 2 diabetes and an HbA1C equal to or greater than 8% using GLP-1 receptor agonists experienced a significant improvement in their HbA1C (-1.5%) at 6 months following the addition of Abbott’s FreeStyle Libre technology to their treatment. Investigators pointed out these trends were consistent across subgroups defined by GLP-1 duration, GLP-1 type, or insulin therapy type.

The next topic of interest for the final ATTD 2024 recap episode was once-weekly insulins, which were the subject of a Friday morning session at the meeting. Chaired by Chantal Mathieu and , the session brought practitioners and diabetes care and education specialists updates on once-weekly insulin codec, which Novo Nordisk announced received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use in late March, and once-weekly insulin efsitora alfa from Eli Lilly and Company. These updates were delivered by Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, and Juan Frias, MD, medical director and principal investigator of National Research Institute, respectively. These presentations were followed by an insight into CGM derived data on weekly insulins from Chantal Mathieu, MD, PhD, professor of medicine at the Katholieke Universiteit Leuven and vice president of the European Association for the Study of Diabetes.

Continuous Ketone Monitoring & Artificial Intelligence in Diabetes

The final 2 topics of discussion for the episode centered around data and presentations from the meeting on a pair of developing areas in diabetes care in continuous ketone monitoring and use of artificial intelligence. The portion of the discussion on continuous ketone monitoring centers around a presented by Jennifer Sherr, MD, PhD, associate professor in Pediatrics (Endocrinology) at Yale School of Medicine, detailing the effects of a dual continuous glucose/ketone monitor from Abbott in a cohort of 23 patients.

Before concluding the episode, hosts touch upon the subject of artificial intelligence in diabetes management. As Isaacs describes in the episode, this portion is prompted by key points in a presentation from Tadej Battelino, MD, PhD, ATTD 2024 co-chair and head of the Department of Endocrinology, Diabetes & Metabolism at the University of Ljubljana. In the presentation, Battelino described multiple scenarios where artificial intelligence is being used to improve care, including predicting risk of adverse outcomes.

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

In this episode, hosts discuss GLP-1 RA use and CGM technology, updates in once-weekly insulins, the concept of continuous ketone monitoring, and practical application of artificial intelligence into care. 

Natalie Bellini, DNP, FNP-BC, BC-ADM, CDCE

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