Real-world evidence is what tells you whether a Phase 3 result holds up in routine care. Coverage on this site has leaned on Truveta's EHR network, IQVIA, and several academic registry analyses — particularly for GLP-1 outcomes outside trial conditions.
Key reads: the Truveta EHR analysis at OMA 2026 reproducing SURMOUNT-5's tirzepatide-vs-semaglutide signal at 12 months in routine care; the Mass General Brigham JAMA study of 90,000+ HFpEF patients on semaglutide and tirzepatide; the AAN 2026 living systematic review of GLP-1 dementia incidence in 2+ million diabetics; and the Foundayo IQVIA launch tracker through retail pharmacy.
Stories here cover the registry analyses, the Truveta and IQVIA data drops, and the policy implications. See #clinical-trial for trial-side coverage.
Among Clalit Health Services members without diabetes who began Wegovy between January and May 2025, 36.5% had stopped by six months and 67.6% by one year, defined as a gap of more than 60 days. Members of the Arab population sector (HR 1.65), people with low socioeconomic status, and smokers were more likely to stop. Staying on the 0.25 mg starting dose at day 90 was also linked to stopping, though much less so after accounting for early refills. After Clalit added tirzepatide coverage in December 2025, 8.6% of eligible members started it.
Inselspital Bern researchers matched household loyalty-card data from two major Swiss grocers for 56 adults with obesity and 92 normal-weight controls. After starting a GLP-1 drug, the obesity group's purchases shifted toward protein, fiber, fruit, vegetables, and unprocessed foods at 5 months, but by 10 months they no longer differed meaningfully from before treatment. The authors note the small sample and household-level data limit precision.
A Brigham and Women's Hospital-led target trial emulation used two U.S. commercial claims databases to compare adults who started either drug between June 2022 and June 2025. Over a median 5.1 months, heart failure hospitalizations ran 19.7 versus 25.5 per 1,000 person-years (HR 0.80), but deaths were similar (HR 0.99). The study is observational with short follow-up.
Researchers across five University of California medical centers reported in the Journal of Diabetes Science and Technology on October 28, 2026 a target-trial emulation comparing adults with type 2 diabetes who started a GLP-1 drug with matched starters of sulfonylureas, SGLT2 inhibitors, or DPP-4 inhibitors, followed for up to five years. Of 181 outcomes screened, 118 associations held up in the authors' checks: 65 lower risks, including heart attack (hazard ratio 0.53) and kidney inflammation (0.73), and 53 higher risks, including osteoarthritis (1.48), stress fractures (1.68), diverticular disease, sleep-wake disorders, and menopausal disorders. The study uses health records and shows associations, not cause.
Researchers at Jefferson Einstein Philadelphia Hospital reported in Supportive Care in Cancer on October 27, 2026 a TriNetX study of 61,630 propensity-matched adults with breast cancer who had a mastectomy or underarm lymph node procedure. Coded postmastectomy lymphedema, arm swelling caused by damaged lymph drainage, was recorded in 0.88% of GLP-1 users versus 2.58% of nonusers over up to 650 days (hazard ratio 0.37), an absolute difference of 1.7 percentage points. The study relied on diagnosis codes and cannot show that the drugs prevented lymphedema.
Thomas Jefferson University researchers reported in Diabetes Care on October 27, 2026 a target-trial emulation using 2011-2022 U.S. Renal Data System and Medicare data on 1,312 semaglutide users and 2,601 dulaglutide or liraglutide users with diabetes on maintenance hemodialysis. After weighting, semaglutide was associated with lower risk of death on dialysis (subdistribution hazard ratio 0.82; one-year incidence 11% vs 13%) and all-cause hospitalization (0.91; 57% vs 62%), and more weight loss at one year (4.8% vs 3.4%). The advantage held against dulaglutide but was not statistically significant against liraglutide; the study is observational.
Mount Sinai Hospital breast oncologists reported in Breast Cancer Research and Treatment on October 26, 2026 a retrospective study of 269 patients taking a GLP-1 drug for at least a year alongside adjuvant endocrine therapy for hormone receptor-positive breast cancer. Average weight loss at 12 months was 4.5% (3.9 kg), with 21.3% losing at least 10% and 10.4% at least 15%; semaglutide users lost 5.8% and tirzepatide users 4.7%, while dulaglutide users were unchanged. Patients whose tumors were PR-negative lost more than PR-positive patients (8.2% vs 4.2%), 70.6% had type 2 diabetes, and the single-center design means the comparison with trial results is indirect.
Washington University School of Medicine researchers reported in HAND on October 26, 2026 a TriNetX study of 11,158 matched pairs of adults who had bariatric surgery between January 2015 and February 2026, with or without a GLP-1 drug. Over a median year of follow-up, GLP-1 users had more new carpal tunnel syndrome diagnoses (risk ratio 1.63) and cubital tunnel syndrome diagnoses (2.10) and more nerve-conduction testing (1.43), but carpal tunnel release surgery rates did not differ significantly. The GLP-1 group was younger and had a lower BMI at baseline, and the authors say more work is needed on mechanisms and monitoring.
University of Southern Denmark researchers reported in Diabetes, Obesity and Metabolism on October 25, 2026 a nationwide interrupted time-series study of adults who started semaglutide for weight management between December 2022 and December 2024, comparing prescriptions in the 12 months after with trends from the 24 months before. At 12 months, use was lower than projected for asthma drugs (rate ratio 0.82), topical steroids (0.91), painkillers (0.93), antidepressants (0.93), and topical antifungals (0.92), and blood pressure drugs rose more slowly than expected (0.92). Anxiety medication use rose (1.16) and stayed elevated at two years; a similar drop in glucose-lowering drugs also appeared in a comparison group, so that change may not be due to semaglutide.
Aarhus University Hospital researchers reported in The British Journal of Psychiatry on October 23, 2026 an interrupted time-series analysis of Danish national registers from 1996 to 2023, identifying 3,042 people with schizophrenia who started a GLP-1 receptor agonist. When the drug was started for diabetes, HbA1c, LDL cholesterol, and triglycerides fell by 11.4%, 6.2%, and 14.8%; when started for overweight, they fell by 3.4%, 4.9%, and 12.7%, all statistically significant. The authors used LDL and triglycerides as stand-ins for weight loss and say the results suggest benefits seen in randomized trials in schizophrenia extend to routine care; the design has no comparison group.
A Clalit Health Services study published October 22, 2026 in Diabetes, Obesity and Metabolism followed 13,387 Israelis aged 65 and older with a BMI of 30 or higher and no diabetes who started a GLP-1 drug, comparing 11,121 with sustained use (three or more dispensations) against 2,266 with one or two. BMI category improved in 55% versus 30% (median BMI change of -8% versus -2%; adjusted odds ratio 2.77), HbA1c category improved in 34% versus 20% of the 7,392 with paired tests, and 65% versus 37% of those with prediabetes returned to normal blood sugar. New diabetes diagnoses were 2.5% versus 5.3%; the authors note the retrospective design describes changes after starting treatment and does not prove causation.
Researchers at the University of Arizona College of Medicine-Phoenix reported in The Journal of Knee Surgery on October 22, 2026 a TriNetX study of adults having a first total knee replacement, matching 11,765 who had a GLP-1 prescription in the year before surgery with 11,765 who did not. GLP-1 users had fewer heart attacks (25 vs 47 events; risk ratio 0.53), deep vein thromboses (74 vs 103; 0.72), and venous thromboembolisms (133 vs 172; 0.77), while pulmonary embolism rates did not differ significantly. The study is observational and based on prescription records.
Mayo Clinic Florida researchers led by Dr. Regina Castaneda presented a retrospective study at The Menopause Society's 2026 annual meeting in San Diego (October 20-24) of women over 45 with a BMI above 27, nearly 2,400 taking semaglutide and nearly 1,500 taking tirzepatide. Among semaglutide users, menopause hormone therapy was associated with significantly greater and sustained weight loss; among tirzepatide users, those on hormone therapy initially lost more, but the difference did not reach statistical significance. The release gives no effect sizes, the study is observational and not yet peer reviewed, and Castaneda said it is "too early to draw firm conclusions" and that weight loss is not an indication for hormone therapy.
University of Texas Medical Branch researchers reported in Diabetes, Obesity and Metabolism on October 19, 2026 a MarketScan claims study of 48,658 adults with diabetes or obesity who started injectable semaglutide between 2018 and 2021. The 14.5% who began at 1.0 mg a week or more, above the labeled starting dose, had a 25% higher risk of stopping early (hazard ratio 1.25) and lower one-year persistence, independent of age, obesity status, other illnesses, and cost. High-dose starts were more common among endocrinologists, men, younger patients, and in the West and South.
Researchers at Case Western Reserve University and the Cleveland Clinic's Cole Eye Institute reported in the Journal of VitreoRetinal Diseases on October 17, 2026 a records study of adults with type 2 diabetes and eye follow-up, matching GLP-1 users with users of other diabetes drugs (53,413 pairs at one year, 14,695 at five years). GLP-1 users had a lower risk of any retinal vascular occlusion, a blockage of the eye's blood vessels that can cause vision loss, at one year (hazard ratio 0.66), three years (0.71), and five years (0.79). The authors called for prospective trials, since the design cannot prove the drugs prevented the blockages.
Dermatologists at the Sapienza University of Rome's Latina campus reported in the Journal of Clinical Medicine on October 16, 2026 a retrospective review of 33 adults with obesity and mild to moderate psoriasis who took semaglutide for 18 months. Average PASI, a psoriasis severity score, fell from 9.31 to 5.05, BMI from 32.5 to 28.4, and blood inflammation markers also dropped; 57.6% had mild, short-lived stomach side effects and none stopped treatment. The single-center study had no comparison group, so it cannot separate the drug's effect from weight loss or other care.
Researchers from St. John's Episcopal Hospital and Washington University in St. Louis reported in the Journal of the American Heart Association on October 16, 2026 a TriNetX records study of 218,043 adults with serious mental illness, type 2 diabetes, and obesity who were taking antipsychotic or antidepressant drugs. Compared with matched nonusers, GLP-1 users had lower risks of heart attack, heart failure, and death at one and three years, with absolute risk differences at three years of 1.0, 1.8, and 6.5 percentage points; semaglutide and tirzepatide showed the same pattern. The authors cautioned that serious mental illness is varied and that diagnoses came from administrative records.
University of Pennsylvania orthopedic researchers reported in the Orthopaedic Journal of Sports Medicine on October 16, 2026 a TriNetX study of adults aged 40 to 80 who had arthroscopic rotator cuff repair while taking tirzepatide or semaglutide. Over two years, matched tirzepatide users had a lower rate of a repeat repair (2.83% vs 5.67%; relative risk 0.50) and less opioid and physical therapy use, and users of either drug had about 16% fewer complete re-tears than matched patients on neither. The authors said the data reflect billing codes and health care use, not confirmed tendon healing.