The fields of endocrinology and diabetes management have been charting a new course in recent years as an understanding of the pathophysiology of endocrine disorders and advancements in available pharmacotherapies have buoyed the field into the spotlight. April 2024 continued this trend, with several HCPLive’s most popular stories centered around advancements in endocrinology and diabetes. In our April 2024 endocrinology month in review, we highlight the top headlines and most popular updates, including updates in the therapeutic pipeline as well as news from scientific congresses.

Updates in Incretin Therapies

In what has become a common theme in the world of endocrinology in recent years, new data related to incretin therapies caught the attention of the medical community during the past month. In this section of our month in review, we recap topline results from the SURMOUNT-OSA trial and a retrospective analysis of preoperative GLP-1 receptor agonist use and post-operative respiratory complications.

GLP-1 Receptor Agonists Not Linked to Post-Op Respiratory Complications

A recent analysis from Anjali Dixit, MD, MPH, of Penn Medicine, challenges preoperative GLP-1 receptor agonist withholding in type 2 diabetes patients undergoing emergency surgery. The study included 23,679 patients, with 14.8% on GLP-1 RAs. The primary outcome of interest for the study was a composite of aspiration pneumonitis, postoperative respiratory failure, and/or admission to the intensive care unit through 7 postoperative days.

Results showed similar rates of postoperative complications between groups, with an overall incidence of 3.5% in the GLP-1 RA group and 4.0% in the non-GLP-1 RA group (OR, 0.85; 95% CI, 0.70 to 1.04; P = .12). Further analysis suggested there was no significant difference in likelihood of respiratory complications (OR, 1.03; 95% CI, 0.82 to 1.29; P = .80).

Tirzepatide Shows Benefit in Obstructive Sleep Apnea

Eli Lilly and Company announced topline data from their phase 3 SURMOUNT-OSA trial, which examined use of tirzepatide (Zepbound) in patients with obesity and obstructive sleep apnea (OSA). Composed by a pair of trials named SURMOUNT-OSA Study 1 and SURMOUNT-OSA Study 2, topline results show tirzepatide significantly reduces apnea-hypopnea index (AHI) in OSA patients, regardless of PAP therapy.

According to an April 17, 2024 announcement, results of the trial, which will be presented in full at the American Diabetes Association's 84th Scientific Sessions, indicate use of tirzepatide was associated with substantial AHI reductions, with reductions of 27.4 and30.4 events per hour among those unable or unwilling to use PAP therapy and those using PAP therapy, respectively.

Diabetes in the Headlines

Evidence of the growing public health burden imposed by diabetes and the blossoming therapeutic pipeline of antidiabetes agents, diabetes-related topics and data have become major points of discussion in scientific congresses beyond the world of endocrinology in recent years. That has continued in 2024. In this portion of our month in review, we acknowledge the top headlines related to diabetes management from the American College of Physicians (ACP) and American College of Cardiology (ACC) flagship meetings.

STEP HFpEF DM: Semaglutide 2.4 mg Improves Functional Status, Symptoms in Patients with Diabetes, HFpEF

Presented at ACC.24, STEP HFpEF DM 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. The trial had dual primary endpoints, which were change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and change in body weight.

Results of the primary outcome analysis indicated use of semaglutide was associated with significant benefit relative to placebo therapy for both mean change from baseline in KCCQ-CSS (Estimated treatment difference [ETD], 7.3 points; 95% CI, 4.1 to 10.4; P < .001) and body weight (ETD, −6.4 percentage points; 95% CI, −7.6 to −5.2; P < .001). Secondary outcomes analysis provided evidence of benefit with semaglutide 2.4 mg relative to placebo for change in 6-minute walk distance (estimated between-group difference, 14.3 meters; 95% CI, 3.7 to 24.9; P = .008), the hierarchical composite endpoint (win ratio, 1.58; 95% CI, 1.29 to 1.94; P < .001), and change in CRP level (estimated treatment ratio, 0.67; 95% CI, 0.55 to 0.80; P < .001).

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

Empagliflozin Misses Primary Endpoint in Post-MI Patient Population, EMPACT-MI Trial

EMPACT-MI was designed as an event-driven, double-blind, randomized, placebo-controlled trial and randomized 6522 patients in a 1:1 ratio to empagliflozin or placebo in addition to standard of care within 14 days of admission for an acute myocardial infarction. The primary outcome of interest for the EMPACT-MI trial was a composite of first hospitalization for heart failure and all-cause mortality assessed in a time-to-first-event analysis.

Results of the primary outcome analysis suggested a first heart failure hospitalization or death occurred among 9.1% (n=267) of the placebo arm and 8.2% (n=298) of the empagliflozin arms, with incidence rates of 6.6 and 5.5 events, respectively, per 100 patient-years (HR, 0.90; 95% CI, 0.76 to 1.06; P= .21). Analysis of individual components of the primary outcome indicated a first hospitalization for heart failure occurred among 4.7% (n=153) of the placebo arm and 3.6% (n=118) of the empagliflozin arm (HR, 0.77; 95% CI, 0.60 to 0.98).

Related: Don't Miss a Beat: EMPACT-MI at ACC.24, with Javed Butler, MD

ACP's New Type 2 Diabetes Guidance Recommends SGLT2is, GLP-1 RAs as Second-Line to Metformin

At their Internal Medicine Meeting 2024, the ACP released updated recommendations for type 2 diabetes management. The pair of recommendations reflect the findings from a systematic review and network meta-analysis and cost-effectiveness analysis assessing the value of available data on therapeutics options both as monotherapies and in combination with metformin.

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).

Related: Diabetes Dialogue: 2024 ACP Type 2 Diabetes Recommendations

Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for Greene include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Relevant disclosures for Butler include AstraZeneca, Bayer Healthcare, Boehringer Ingelheim Pharmaceuticals, Eli Lilly and Company, and others. 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, Sanofi, and others.