ENDO 2025: GLP-1 Receptor Agonists as Multisystem Therapies in Type 2 Diabetes Management

GLP-1 receptor agonists are transforming the management of type 2 diabetes, with growing evidence supporting their benefits beyond glycemic control. At the ENDO 2025 conference in San Francisco, California, a symposium titled “Complex Cases Incorporating GLP-1 Receptor Agonists Into Holistic Management of Type 2 Diabetes” brought together experts to explore the expanding role of GLP-1 receptor agonists in cardiometabolic care.

In this interview with Pharmacy Times®, Jennifer Goldman, PharmD, CDCES, BC-ADM, FCCP, professor of pharmacy practice and clinical pharmacist at Massachusetts College of Pharmacy and Health Sciences in Boston, discusses key highlights from the session she co-presented with Jennifer Green, MD, a professor of medicine and member in the Duke Clinical Research Institute at the Duke University School of Medicine in Durham, North Carolina, and Jay Shubrook, DO, BC-ADM, FACOFP, FAAFP, a professor of the Primary Care Department at Touro University California in Vallejo. Goldman shares insights into the pleiotropic benefits of GLP-1 receptor agonists across cardiovascular, renal, hepatic, and functional domains; offers practical guidance on overcoming clinical and access barriers; and previews investigational incretin therapies that may redefine the standard of care for patients with type 2 diabetes and related metabolic conditions.

Pharmacy Times: Could you discuss your presentation at ENDO 2025?

Jennifer Goldman, PharmD, CDCES, BC-ADM, FCCP: At ENDO 2025, I had the pleasure of co-presenting a symposium titled “Complex cases incorporating GLP-1 receptor agonists into holistic management of type 2 diabetes,” and I did this alongside 2 outstanding colleagues, Jennifer Green, MD, [of] Duke University School of Medicine and Jay Shubrook, DO, BC-ADM, FACOFP, FAAFP, from Touro University California. Together, we explored the evolving role of GLP-1 receptor agonists using real-world case discussions, clinical trial updates, and interactive learning. This session was coordinated and presented through [Medical Learning Institute] education.

Pharmacy Times: GLP-1 receptor agonists are highly effective, yet still underused—what are the most common clinical or access barriers you see in practice?

3D rendering of the GLP-1 molecule. Image Credit: © Your Hand Please - stock.adobe.com

Goldman: In my clinical practice, the most significant barriers to GLP-1 receptor agonist use are related to access and cost. Despite the strong evidence base and inclusion in guidelines, these therapies often require prior authorizations, peer to peer reviews or step therapy, especially for patients on Medicare. This creates frustrating delays in care. Additionally, there's still a misconception among some prescribers that GLP-1 receptor agonists are strictly for glycemic control, and this overlooks their benefits for cardiovascular, renal, and hepatic outcomes. This is one of the topics—the main topic of the session we just did at ENDO 2025—is really the pleiotropic effects of these therapies. So, on the patient side, barriers include even fear of side effects and unrealistic expectations about weight loss.

Pharmacy Times: How has the growing body of evidence supporting GLP-1 receptor agonists for cardiovascular and renal benefits impacted your approach to type 2 diabetes treatment?

Goldman: The expanding evidence base has dramatically transformed how I manage patients with type 2 diabetes. I now see GLP-1 receptor agonist as comprehensive cardiometabolic renal agents, not just glucose lowering agents. In addition to the well-established cardiovascular and renal benefits seen in trials like SELECT [NCT03574597], FLOW [NCT03819153], and SUMMIT [NCT04847557], newer data continue to broaden the scope of that impact. So, for example, the ESSENCE trial [NCT04822181] demonstrated that semaglutide [Ozempic and Wegovy; Novo Nordisk] significantly improved liver histology in patients with metabolic dysfunction associated steatohepatitis [MASH], showing both resolution of steatohepatitis and improvement in fibrosis without worsening the other, and this is particularly important to people with type 2 diabetes and [metabolic dysfunction-associated steatotic liver disease (MASLD)], and this is a population that we frequently care for.

Meanwhile, the STRIDE trial [NCT04560998] improved walking distance and functional outcomes in people with type 2 diabetes and symptomatic peripheral artery disease, and that adds a vascular dimension to GLP-1 benefits that we haven't addressed in previous trials. So taken together, these findings reinforce GLP-1 receptor agonists as foundational therapy in people with type 2 diabetes and comorbid conditions far beyond glycemic control alone. In a recent pooled analysis that included SELECT, FLOW, STEP-HFpEF [NCT04788511], STEP HFpEF DM [NCT04916470] trials showed that semaglutide improved symptoms and functional status in people with heart failure and preserved a mildly reduced ejection fraction.

Similarly, the SUMMIT trial demonstrated that tirzepatide [Mounjaro and Zepbound; Eli Lilly and Company] significantly reduced the risk of cardiovascular death or worsening heart failure in patients with [heart failure with preserved ejection fraction (HFpEF)], and consistent benefits were seen in individuals both with and without type 2 diabetes. So, these findings further strengthen the role of GLP-1–based therapies in heart failure management.

Pharmacy Times: Can you share a memorable clinical case that illustrates the difference GLP-1 RAs can make when used appropriately?

Goldman: One case that comes to mind is a 42 year old woman with type 2 diabetes and MASLD. Her A1c had recently risen to 8.2% and she was scheduled for elective surgery, and that had to be postponed due to that elevation. So GLP-1 receptor agonist therapy was initiated, it was titrated over the next few months, and she experienced meaningful reductions in blood sugar and weight, and as a result, she was cleared for surgery. But this case really underscores how timely intervention with GLP-1 receptor agonists can address urgent metabolic concerns and help patients reach their personal health goals more quickly. So also, although not on label yet, we have this growing evidence to support their use in MASLD, and GLP-1 based therapies in this population is supported by guidelines due to all this evidence.

Pharmacy Times: Are there any new or investigational GLP-1-based agents you're particularly excited to discuss at the symposium?

Goldman: I'm especially enthusiastic about the wave of next generation incretin-based therapies currently in development. So, agents like semaglutide and tirzepatide have already shown promise in improving glycemic control and weight and hepatic outcomes and functional status in patients with heart failure. But there's more exciting things and more multi-receptor agonists now in clinical trials.

So, from our session, we discussed a wide array of combination targeting, GLP-1, [glucose-dependent insulinotropic polypeptide (GIP)], glucagon, amylin, even GLP-2 receptors. So, for example, retatrutide [Eli Lilly and Company] combines GLP-1, GIP, and glucagon receptor agonism, and that's showing reductions in steatohepatitis, inflammation, and substantial weight loss. Survodutide [BI 456906; Boehringer Ingelheim] similarly, combines GLP-1 and glucagon receptor activity with liver-directed effects in MASH. [Cagrilintide/semaglutide (CagriSema; Novo Nordisk)] and petrelintide [ZP8396; Zealand Pharma] paired GLP-1 receptor agonists with amylin or [dual amylin and calcitonin receptor agonist] activity to improve tolerability, lean muscle mass retention, and weight loss. So [maridebart cafraglutide (MariTide; Amgen)] and AT-7687 [Antag Therapeutics] incorporate GIP receptor antagonism or GIP-only activity for further metabolic flexibility. So, these investigational therapies reflect a strategic evolution, one that could address the full spectrum of metabolic disease, from insulin resistance and obesity to fatty liver, cardiovascular risk, and even functional impairments. So, we’re no longer targeting just A1c, so it's external to just those glycemic effects; we're aiming for true disease modification across the multi-system.

It's also worth highlighting that semaglutide has demonstrated benefits in HFpEF in pooled analysis from SELECT and STEP-HFpEF, while tirzepatide improved cardiovascular outcomes [and] reduced heart failure events in the SUMMIT trial. So, this expands the utility of GLP-1 based therapies to patients with heart failure, especially those with obesity and/or type 2 diabetes.

Pharmacy Times: Your session uses case-based storytelling and interactive learning—what key takeaways do you hope attendees walk away with?

Goldman: I hope attendees left this session with 3 main takeaways. First, that GLP-1 receptor agonists are not just for glycemic control. They are versatile agents with cardio-renal-hepatic benefits. Second, that it's entirely possible to initiate and titrate these agents safely with good patient communication and support. Third, individualized evidence-based prescribing, especially using guideline-driven case approaches, can improve the outcomes in patient satisfaction. So, these medications should not be an afterthought. For many patients, they should be considered first-line therapy.

In the presence of comorbidities, this is supported by the [American Diabetes Association] standards of care, especially in patients with [atherosclerotic cardiovascular disease], heart failure, [chronic kidney disease], obesity, and MASLD—now with that emerging data—as well as peripheral artery disease.

Pharmacy Times: What pearls of advice would you give to clinicians looking to build confidence in prescribing GLP-1 RAS for broader patient populations?

Goldman: My advice would be to start low and titrate slowly to manage side effects, especially the [gastrointestinal] symptoms. Set realistic expectations with patients and use shared decision making to guide the treatment choices. Also, don't wait for the A1c to climb or complications to arise. Early initiation of GLP-1 receptor agonists can help prevent the progression. And finally, lean on your interdisciplinary team, [such as] pharmacists, for example. Pharmacists can help navigate insurance barriers, support adherence, and manage side effects, making the prescribing process much smoother.