ENDO 2026 Recap — GLP-1 and Peptide Readouts from the Endocrine Society Meeting

ENDO 2026, the Endocrine Society’s annual meeting, ran June 13–16, 2026, in Chicago, Illinois (ENDO 2026 program). Several of the most discussed presentations centered on GLP-1 receptor agonists and next-generation metabolic peptides — spanning behavior, safety, combination efficacy, real-world adherence, and early-stage oral formulations. A note before the readouts: most of the items below are conference presentations, posters, and abstracts, many of which are not yet peer-reviewed or published in full. We label each item’s evidence stage and report numbers exactly as the primary source states them.

Physical Activity Fell After Starting a GLP-1 — the Muscle-Preservation Angle

A retrospective cohort study found that adults with obesity moved less, not more, after starting a GLP-1 medication such as semaglutide or tirzepatide. The team, led by Sajana Maharjan, M.D., of HSHS St. John’s Hospital (Springfield, Illinois), used the NIH’s All of Us Research Program, which links electronic health records with participants’ Fitbit data.

Of 1,950 adults with obesity who started a GLP-1, 753 had enough wearable-device data to analyze (78.6% female; mean age 52.7 years). Over the pre-vs-post comparison:

• Mean daily steps fell from 5,047 to 4,487 — a decline of 560 steps per day
• Moderate-to-vigorous physical activity fell from about 28 to 22 minutes per day — a decline of roughly 6 minutes per day

Why it matters: GLP-1 therapy reduces lean (muscle) mass alongside fat, so a drop in activity compounds the muscle-preservation challenge rather than offsetting it. As Maharjan put it, “While many assume that weight loss leads naturally to increased physical activity, our study suggests otherwise.”

Evidence stage: Observational, retrospective pre-post cohort — shows an association, not causation, and cannot prove the medication caused the activity drop. Presented at ENDO 2026; not yet peer-reviewed. Source: Endocrine Society press release.

GLP-1s and Male Fertility — No Long-Term Harm, Possible Benefit

A systematic review of randomized controlled trials concluded that GLP-1s do not harm male hormones, sexual function, or sperm quality after longer-term use — and may help in men with obesity-related low testosterone. The work, led by Pratibha Natesh, M.B.B.S., of Warwick Medical School and University Hospitals Coventry and Warwickshire (UK), screened published RCTs comparing GLP-1s with another treatment or placebo in men aged 18–65.

Five trials met the eligibility criteria. Reported findings:

• No negative impact on hormones, sexual function, or sperm quality across the trials
• Liraglutide (16 weeks): increases in testosterone and related hormones
• Semaglutide (24 weeks): testosterone and hormone levels stayed stable
• Semaglutide: improvements in sperm shape and cholesterol

Natesh framed it as support for “a shift away from prescribing testosterone replacement in men with obesity and low testosterone and toward treating the underlying cause — excess weight and poor metabolic health.”

Evidence stage: Systematic review of existing RCTs — only five trials, small and with varying results; the authors note benefits are likely indirect (via weight loss) and that GLP-1s were not evaluated as treatments for male infertility. Larger, better-designed studies are still needed. Presented at ENDO 2026. Source: Endocrine Society press release.

CagriSema Meta-Analysis (Abstract SUN-726)

A systematic review and meta-analysis pooled randomized trial data on CagriSema — the once-weekly combination of the amylin analog cagrilintide and semaglutide — for obesity, evaluating both efficacy and safety. The poster (abstract SUN-726, Burkhardt da Silveira et al., Northwestern Medicine McHenry Hospital / Rosalind Franklin University) reported that, across the pooled RCTs, CagriSema produced greater weight loss than semaglutide alone, with a tolerability profile consistent with the GLP-1/amylin class (predominantly gastrointestinal side effects).

For the underlying trial magnitudes, the pivotal REDEFINE program data were published in the New England Journal of Medicine. We are not quoting a single pooled effect size here because we could not confirm SUN-726’s specific pooled numbers against a primary source.

Evidence stage: Meta-analysis of existing randomized controlled trials — a secondary, pooled analysis, not new trial data. Presented as a poster at ENDO 2026. Source: ENDO 2026 abstract program (SUN-726).

Real-World Adherence — GLP-1 Use Is More Start-and-Stop Than Assumed

One of the larger real-world readouts came from Sainikhil Sontha, M.S., of Boston University School of Public Health, using Komodo Health U.S. claims data (January 2019–June 2025) on more than 60,000 adults aged 18–64 with type 2 diabetes and a BMI of 25 kg/m² or higher who were taking liraglutide, semaglutide, or tirzepatide.

• Of those who stopped, 41.5% restarted within one year, and 58% restarted within two years
• Patients on tirzepatide were 41% less likely to discontinue than those on liraglutide
• Patients on semaglutide were 28% less likely to discontinue than those on liraglutide

Sontha’s takeaway was that GLP-1 “use is more start-and-stop than most people assumed,” and that stopping early may mean “missed opportunities” to prevent downstream cardiovascular and kidney complications.

Evidence stage: Retrospective insurance-claims cohort — an association in administrative data, not a controlled trial. Presented at ENDO 2026. Source: Endocrine Society press release.

Entera Bio — Preclinical Oral Peptides (EB618 and EB612)

Entera Bio brought early-stage data on two oral peptide tablets built on its oral-delivery platform, co-developed with OPKO Health:

• EB618 — a first-in-class oral GLP-1/glucagon dual agonist (oxyntomodulin) for obesity. Entera reported pharmacokinetic data for the oral tablet in non-human primates, describing dose-proportional pharmacokinetics and an effect on blood glucose.
• EB612 — a first-in-class oral long-acting PTH(1-34) tablet for hypoparathyroidism, reported to show robust bioavailability and sustained increases in calcium across three preclinical models, with an IND filing expected in late 2026.

Entera separately had single-tablet data for EB613 (its oral PTH(1-34) anabolic for osteoporosis) selected as a late-breaking oral presentation.

Evidence stage: Preclinical — the EB618 and EB612 data are from animal/non-human-primate models, the earliest research stage, with no human efficacy data for these programs yet. Sources: Entera Bio Q1 2026 update and ENDO 2026 data release (GlobeNewswire).

What It Means

The conversation is shifting from “how much weight” to “how well.” The headline efficacy questions are largely settled for this class; ENDO 2026’s most useful signals were about quality of weight loss (muscle preservation, the activity decline), safety reassurance (male fertility), and durability (adherence and restart patterns).

Combination and triple-agonist momentum continues. The CagriSema meta-analysis adds pooled context to the amylin-plus-GLP-1 approach, while the broader field keeps moving toward multi-receptor agonists — see our coverage of retatrutide’s TRIUMPH-1 Phase 3 results.

Oral formulations are the next frontier — at very different maturities. The oral GLP-1 readouts from ECO2026 were clinical-stage; Entera’s oral peptides are still preclinical. Both point the same direction, but they are not at the same evidence level.

Access and policy remain the backdrop. Much of the U.S. debate this year has been regulatory rather than clinical — for example, the FDA’s move on 503B bulk-compounding of GLP-1s.

As always with conference data: abstracts and posters are early disclosures. Treat the findings above as provisional until they appear as peer-reviewed, full-length publications.