APhA2026: GLP-1 Therapies Are Rewriting the Rules of Metabolic Disease

Glucagon-like peptide-1 (GLP-1) receptor agonists are no longer a diabetes drug class with a useful side effect. In just a few years, they have become one of the most consequential drug classes in modern medicine, with an evidence base expanding faster than many pharmacists can track. At the 2026 American Pharmacists Association Annual Meeting and Exposition (APhA2026) in Los Angeles, California, Emily Eddy, PharmD, BCACP, BC-ADM, CDCES, associate professor of pharmacy practice and director of clinical services at Ohio Northern University in Ada, delivered a rapid-fire, evidence-packed session surveying the current landscape of GLP-1 and GLP-1/glucose-dependent insulinotropic polypeptide (GIP) therapies—from newly approved formulations to phase 3 data on emerging indications that once seemed far outside the incretin orbit.¹

"This has gone, when I was in pharmacy school [and] they were just coming out, from ‘oh, this is helpful, these are good medications, we kind of like them,’ to ‘this is a real game changer,’" Eddy told attendees. "This has really changed the way we practice. And I've now approached patients not just treating diabetes but treating underlying metabolic problems."¹

A New Oral Era

Eddy opened with a tour of the newly available and near-approval oral and injectable agents that are reshaping the GLP-1 formulary. Oral semaglutide 25 mg (Wegovy pill; Novo Nordisk), available since January 2026, marked a significant formulation advance over the earlier oral semaglutide available for diabetes. The product uses a technology called salcaprozate sodium, featuring a tablet design that locally raises pH to improve absorption and eliminates the peptide degradation problem that made earlier oral GLP-1 options less bioavailable. In the phase 3 OASIS 4 trial (NCT05564117), the 25-mg tablet delivered a mean weight loss of 13.6% in patients with obesity and without diabetes, with 79.2% of participants achieving at least 5% weight loss, vs 31.1% with placebo.^1,2

Also prominently featured was orforglipron (Foundayo; Eli Lilly and Company), a first-in-class oral, small-molecule, nonpeptide GLP-1 receptor agonist awaiting FDA action. Unlike oral semaglutide, orforglipron carries no fasting or water restrictions, a meaningful practical advantage for patients. In the phase 3 ATTAIN-1 trial (NCT05869903) in adults with obesity and without diabetes, orforglipron delivered dose-dependent mean weight loss of 7.5% (95% CI, –8.2% to –6.8%), 8.4% (95% CI, –9.1% to –7.7%), and 11.2% (95% CI, –12.0% to –10.4%) at the 6-mg, 12-mg, and 36-mg doses, respectively, vs 2.1% (95% CI, –2.8% to –1.4%) with placebo. In the phase 3 ACHIEVE-3 head-to-head trial (NCT06045221), orforglipron was noninferior—and for the 36-mg dose, superior—to oral semaglutide in hemoglobin A_1C reduction in patients with type 2 diabetes (T2D).^1,3,4

"It is an oral, nonpeptide GLP-1 receptor agonist that has demonstrated clinically meaningful weight loss in clinical trials," Eddy noted in summarizing orforglipron's profile, reflecting the trial data directly. Eddy flagged orforglipron as a particularly relevant agent for pharmacists to watch, because its convenience profile could improve adherence and broaden access for patients who are injection-averse or poorly adherent to current oral options.¹

Eddy also highlighted high-dose injectable semaglutide 7.2 mg, studied in the phase 3 STEP-UP trial program (NCT05646706). In patients without diabetes, the 7.2-mg dose produced a mean weight loss of 18.7% vs 3.9% with placebo (estimated treatment difference, –3.1%; 95% CI, –4.7% to –1.6%; P < .0001)—surpassing the currently available 2.4-mg dose—and 13.2% in those with type 2 diabetes.⁵

For the pipeline, she covered cagrilintide/semaglutide (CagriSema; Novo Nordisk), which showed approximately 20.4% weight loss (estimated difference, –17.3%; 95% CI, –18.1% to –16.6%; P < .001) in the phase 3 REDEFINE-1 trial (NCT05567796) and has a new drug application submitted as of December 2025; maridebart cafraglutide (MariTide; Amgen), a once-monthly injectable GIP antagonist/GLP-1 agonist showing 12.3% (95% CI, –15.0% to –9.7%) to 16.2% (95% CI, –18.9% to –13.5%) weight loss in a phase 2 trial (NCT05669599); survodutide, a dual glucagon/GLP-1 agonist with phase 3 (NCT06309992) results pending; and retatrutide, the triple GIP/GLP-1/glucagon agonist showing up to 28.7% weight loss in the phase 3 TRIUMPH-4 trial (NCT05931367).^6-9

"If we're not just chasing the highest number, a more convenient option could be beneficial in a certain patient population," Eddy said of longer-acting or oral options, noting that monthly injectables could appeal particularly to patients who struggle with weekly injection adherence.¹

Beyond Weight Loss: The Evidence Is Piling Up

The session's most forward-looking section focused on the rapidly accumulating evidence for GLP-1 therapies across a wide range of indications outside diabetes and obesity. Eddy emphasized that although excitement is warranted, not all emerging evidence rises to the level of current clinical recommendations. She highlighted that pharmacists are well positioned to help patients and providers navigate that distinction.

In liver disease, Eddy highlighted the phase 3 ESSENCE trial (NCT04822181), in which semaglutide 2.4 mg produced resolution of steatohepatitis without worsening fibrosis in 62.9% of patients with biopsy-confirmed metabolic dysfunction–associated steatohepatitis (MASH) with fibrosis stage 2 or 3, vs 34.3% with placebo (estimated difference, 28.7%; 95% CI, 21.1%-36.2%; P < .001). The FDA granted accelerated approval for this indication in August 2025, and the 2026 American Diabetes Association Standards of Care now recommend GLP-1 receptor agonists as preferred agents for patients with type 2 diabetes and biopsy-proven MASH or high fibrosis risk.^10-12

"We're not just ‘not making it worse’; we're having resolution of some of the cirrhosis and scarring," Eddy explained of the ESSENCE findings, reflecting on the genuine improvement in key markers of liver damage.¹

In chronic kidney disease (CKD), Eddy reviewed the phase 3 FLOW trial (NCT03819153) data demonstrating that semaglutide 1 mg reduced the risk of major kidney events by 24% (HR, 0.76; 95% CI, 0.66-0.88) in patients with type 2 diabetes and CKD, while also slowing annual estimated glomerular filtration rate decline, a finding that resulted in a dedicated indication for semaglutide in this population.^13,14

"I used to tell students: kidneys, that's the difference between an SGLT2 and a GLP-1," Eddy said with a laugh. "And now that's not even the difference anymore."¹

In obstructive sleep apnea (OSA), tirzepatide's (Zepbound; Eli Lilly and Company) phase 3 SURMOUNT-OSA trial (NCT05412004) demonstrated a reduction of 25.3 (95% CI, –29.3 to –21.2) to 29.3 (95% CI, –33.2 to –25.4) events per hour in apnea-hypopnea index (AHI) vs approximately 5 with placebo, alongside 17% to 20% body weight reduction. This data supported tirzepatide's indication for OSA, the only GLP-1 with such an indication.^15,16

Eddy also addressed an area she described as particularly intriguing despite the early evidence stage. In alcohol use disorder (AUD), a target trial emulation study of more than 120 million patients found that tirzepatide was associated with a significant relative reduction in AUD incidence vs DPP-4 inhibitors in patients with type 2 diabetes (HR, 0.40; 95% CI, 0.29-0.75), with similar signals for semaglutide and liraglutide. The proposed mechanism involves GLP-1 receptor expression in reward-related brain regions dampening dopaminergic drug-reward signaling.¹⁷

"I don't think we have enough data to say everyone who has a substance use disorder, put them on a GLP-1," Eddy noted, "But it is an area that is worth exploring."¹

And in Alzheimer disease (AD), the EVOKE (NCT04777396) and EVOKE+ phase 3 trials of oral semaglutide 14 mg in patients with early symptomatic AD showed no statistically significant difference in Clinical Dementia Rating Scale Sum of Boxes scores vs placebo—a finding Eddy contextualized carefully. "Not to say this isn't an area to continue to explore," she said. "The data [are] just not quite strong enough right now."^1,18

Pharmacists at the Center

Throughout the session, Eddy consistently returned to the pharmacist's role. Pharmacists are not just dispensers of these agents; they are clinical navigators who can help patients use them correctly, counsel on evolving indications, correct misinformation, and ensure that medication is never pursued in isolation from diet, lifestyle, and monitoring. She acknowledged, in response to an audience member's question, that access and coverage remain pressing equity concerns, particularly for patients in federally qualified health center settings or those whose insurance coverage has lapsed.¹

"People are inundated with information about GLP-1s right now," Eddy said in closing. "We're really poised to help people navigate all of that health information and make sure we're making the right choices."¹

REFERENCES

1. Eddy E. The real stars of Beverly Hills: GLP-1s taking the spotlight. Presented at: American Pharmacists Association Annual Meeting & Exposition; March 29, 2026; Los Angeles, CA.

2. Wharton S, Lingvay I, Bogdanski P, et al; OASIS 4 Study Group. Oral semaglutide at a dose of 25 mg in adults with overweight or obesity. N Engl J Med. 2025;393(11):1077-1087. doi:10.1056/NEJMoa2500969

3. Wharton S, Aronne LJ, Stefanski A, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. N Engl J Med. 2025;393(18):1796-1806. doi:10.1056/NEJMoa2511774

4. Rosenstock J, Yabe D, Cox D, et al; ACHIEVE-3 Investigators. Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial. Lancet. 2026;407(10534):1147-1160. doi:10.1016/S0140-6736(26)00202-3

5. Wharton S, Freitas P, Hjelmesæth J, et al; STEP UP Trial Group. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):949-963. doi:10.1016/S2213-8587(25)00226-8

6. Garvey WT, Bluher M, Osorto Contreras CK, et al; REDEFINE 1 Study Group. Coadministered cagrilintide and semaglutide in adults with overweight and obesity. N Engl J Med. 2025;393(7):635-647. doi:10.1056/NEJMoa2502081

7. Jastreboff AM, Ryan DH, Bays HE, et al. Once-monthly maridebart cafraglutide for the treatment of obesity—a phase 2 trial. N Engl J Med. 2025;393(9):843-857. doi:10.1056/NEJMoa2504214

8. A study to test whether survodutide helps people living with obesity or overweight and with a confirmed or presumed liver disease called non-alcoholic steatohepatitis (NASH) to reduce liver fat and to lose weight. ClinicalTrials.gov. Updated March 13, 2026. Accessed March 29, 2026. https://clinicaltrials.gov/study/NCT06309992

9. Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial. News release. Eli Lilly and Company. December 11, 2025. Accessed March 29, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average

10. Sanyal AJ, Newsome PN, Kliers I, et al; ESSENCE Study Group. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. N Engl J Med. 2025;392(21):2089-2099. doi:10.1056/NEJMoa2413258

11. FDA approves treatment for serious liver disease known as ‘MASH.’ FDA. August 15, 2025. Accessed March 29, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash

12. American Diabetes Association Professional Practice Committee for Diabetes. Summary of revisions: standards of care in diabetes—2026. Diabetes Care. 2026;49(1 suppl 1):S6-S12. doi:10.2337/dc26-SREV

13. Perkovic V, Tuttle KR, Rossing P, et al; FLOW Trial Committees and Investigators. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347

14. Munz K. FDA expands semaglutide use for CV, kidney risks in T2D, CKD. AJMC. January 28, 2025. Accessed March 29, 2026. https://www.ajmc.com/view/fda-expands-semaglutide-use-for-cv-kidney-risks-in-t2d-ckd

15. Malhotra A, Grunstein RR, Fietze I, et al; SURMOUNT-OSA Investigators. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391(13):1193-1205. doi:10.1056/NEJMoa2404881

16. FDA approves first medication for obstructive sleep apnea. News release. FDA. December 20, 2024. Accessed March 29, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea

17. Henney AE, Riley DR, Heague M, et al. Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach. Diabetes Obes Metab. 2026;28(1):137-150. doi:10.1111/dom.70169

18. Readout of phase 3 semaglutide trials marks critical moment in Alzheimer research and suggests potential for combination therapies. News release. Alzheimer’s Drug Discovery Foundation. Released November 24, 2025. Accessed March 29, 2026. https://www.alzdiscovery.org/news-room/announcements/readout-of-phase-3-semaglutide-trials-marks-critical-moment-in-alzheimers-research-and-suggests-potential-for-combination-therapies