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Home > Research article > Beyond weight loss: what GLP-1 research found next

Beyond weight loss: what GLP-1 research found next

Beyond weight loss: what GLP-1 research found next

August 30, 2026

Last reviewed 30 August 2026

The most remarkable thing about GLP-1 research since 2023 is not the weight-loss percentages. It is the chain reaction: almost every major trial result has seeded the next round of trials, and a striking number of those trials have ended in new licensed indications. In three years the class has produced regulator-approved treatment for cardiovascular risk, chronic kidney disease, a liver disease and — for the first time in the history of the condition — obstructive sleep apnoea. This article traces the findings beyond weight loss, and the research each one triggered.

Every statement here is a statement about a named trial, a regulator’s decision or a published figure; none is advice. The compounds concerned are prescription-only or investigational medicines that NovoVita does not sell; the head-to-head evidence between them is set out in the companion comparison article.

The heart

SELECT was the trial that changed the class’s standing. It asked whether semaglutide 2.4 mg does anything for people with cardiovascular disease and obesity but no diabetes — 17,604 participants, followed for a mean of 39.8 months (NEJM 2023). Major adverse cardiovascular events occurred in 6.5% on semaglutide against 8.0% on placebo — a hazard ratio of 0.80, a fifth fewer heart attacks, strokes and cardiovascular deaths. Within a year the finding became a licence: the FDA added cardiovascular risk reduction to Wegovy’s label in March 2024, and the MHRA followed in July 2024 — reported as the first UK licence of a weight-management medicine for preventing cardiovascular events.

Heart failure followed. STEP-HFpEF (NEJM 2023; 529 participants with obesity-related heart failure with preserved ejection fraction) recorded a 16.6-point improvement in the KCCQ symptom score against 8.7 on placebo, weight change of −13.3% against −2.6% — and C-reactive protein, a marker of inflammation, fell 43.5% on semaglutide against 7.3% on placebo, a signal now studied in its own right. STEP-HFpEF DM (2024) replicated the result in people with diabetes, and SUMMIT (NEJM 2024) extended it to tirzepatide, which reduced the composite of cardiovascular death or worsening heart failure. A phenotype of heart failure with no approved obesity-targeted therapy acquired two candidate drug classes in eighteen months.

The kidneys

Kidney signals in earlier cardiovascular trials prompted FLOW, the first dedicated GLP-1 kidney-outcomes trial: 3,533 people with type 2 diabetes and chronic kidney disease, semaglutide 1.0 mg against placebo (NEJM 2024). The trial was stopped early for efficacy at a pre-specified interim analysis — the composite of major kidney events fell 24% (hazard ratio 0.76, P=0.0003). In January 2025 the FDA made Ozempic the first GLP-1 with a chronic-kidney-disease indication. A pre-specified analysis of SELECT (Colhoun et al., Nature Medicine 2024) then showed the same direction in people without diabetes: a 22% reduction in the main 5-component kidney composite endpoint.

The liver

The liver work has moved fastest of all. ESSENCE (NEJM 2025) tested semaglutide in biopsy-confirmed MASH — metabolic dysfunction-associated steatohepatitis, the inflammatory fatty-liver disease — with moderate-to-advanced fibrosis: at 72 weeks, 62.9% achieved resolution of steatohepatitis without worsening fibrosis, against 34.3% on placebo, and 36.8% achieved fibrosis improvement against 22.4%. The regulatory cascade ran in three jurisdictions inside eleven months: FDA accelerated approval (August 2025), a conditional EU marketing authorisation under the brand name Kayshild (26 March 2026), and a conditional MHRA approval for the UK (3 July 2026) — with continued approval tied to the trial’s 240-week second part.

The next front is already visible: in a phase 2a substudy (Nature Medicine 2024), retatrutide reduced liver fat by 82.4% in relative terms at the top dose over 24 weeks, with 86% of that arm reaching normal liver-fat content — imaging data rather than biopsy histology, but among the largest liver-fat reductions reported for any pharmacological agent.

Sleep apnoea

SURMOUNT-OSA (NEJM 2024) took tirzepatide into moderate-to-severe obstructive sleep apnoea — 469 adults across two 52-week trials, with baseline apnoea-hypopnoea indices around 50 events per hour. The AHI fell by 25.3 events per hour (against 5.3 on placebo) in participants not using positive airway pressure, and by 29.3 (against 5.5) in those who were. In December 2024 the FDA approved tirzepatide for OSA — the first medicine ever approved for the condition. The EMA reached the same clinical conclusion by a different route in December 2024, folding the OSA data into tirzepatide’s existing weight-management indication.

Joints

STEP 9 (NEJM 2024) enrolled 407 people with obesity and painful knee osteoarthritis: WOMAC pain scores improved by a mean of 41.7 points on semaglutide against 27.5 on placebo, from a baseline of 70.9, alongside 13.7% weight reduction. Retatrutide’s TRIUMPH-4 (topline, December 2025) made knee osteoarthritis a co-primary endpoint and reported pain reduction of 74.3% against 40.3% on placebo alongside 28.7% weight reduction — osteoarthritis pain is now a named indication in Lilly’s planned first filing.

Alcohol, appetite and the reward system

This thread began as user reports and became randomised evidence — the full story of that conversion is told in the companion article on user reports. The research arc: large electronic-health-record studies (Wang, Volkow and colleagues, 2024) found semaglutide use associated with roughly half the incidence of alcohol-use disorder across tens of thousands of patients, with similar signals for tobacco, cannabis and opioids — associations, not proof. A first randomised trial followed (JAMA Psychiatry 2025): in 48 non-treatment-seeking adults with alcohol-use disorder, semaglutide reduced laboratory alcohol self-administration, craving, drinks per drinking day and the trajectory of heavy-drinking days against placebo. Then SEMALCO (The Lancet 2026; 108 treatment-seeking adults with alcohol-use disorder and obesity, on top of cognitive behavioural therapy): heavy drinking days fell 13.7 percentage points more on semaglutide than placebo (P=0.0015). No GLP-1 holds any addiction indication anywhere — but a research question that did not exist five years ago now has further randomised trials registered and running.

“Food noise” travelled the same road: a phrase coined by patients acquired a formal research definition in 2024 — persistent, unwanted, dysphoric thoughts about food — and two validated measurement instruments in 2025. The science is now equipped to test what users described first.

The questions research is answering next

Not every extension succeeded, and the field’s response to its own open questions is itself worth recording. Oral semaglutide did not slow Alzheimer’s progression in the two EVOKE phase 3 trials (3,808 participants; results December 2025) — biomarkers moved, cognition did not. In Parkinson’s, exenatide failed its phase 3 trial (The Lancet 2025) while lixisenatide’s smaller phase 2 had succeeded — different molecules and durations, and an unresolved class question rather than a closed one. On safety, the EMA concluded in June 2025 that the eye condition NAION is a very rare side effect of semaglutide — affecting up to 1 in 10,000, roughly a doubling of a very small baseline risk — and updated the product information.

Two findings turned into whole research programmes. Weight lost on these medicines is partly lean mass — roughly a quarter to two-fifths in published analyses — and the response has been combination trials: in BELIEVE (2025), adding the anti-activin antibody bimagrumab to semaglutide produced 22.1% weight loss of which 92.8% was fat, cutting lean-mass loss from 7.9% to 2.6%. And weight returns when treatment stops — two-thirds of it within a year in the STEP 1 extension; in SURMOUNT-4, participants switched to placebo regained 14.0% while those who continued lost a further 5.5% — which is why maintenance is now a trial endpoint in its own right, including a dedicated retatrutide maintenance trial (TRIUMPH-6). The largest single answer is still in progress: TRIUMPH-Outcomes, a 10,000-participant cardiovascular and kidney outcomes trial of retatrutide.

The chain, drawn out

  • SELECT’s cardiovascular result (2023) → FDA and MHRA cardiovascular licences (2024) → the SELECT kidney analysis (2024).
  • Kidney signals in earlier trials → FLOW (stopped early, 2024) → the first GLP-1 kidney indication (2025).
  • The obesity–heart-failure hypothesis → STEP-HFpEF and STEP-HFpEF DM → SUMMIT with tirzepatide (2024).
  • SURMOUNT weight results → SURMOUNT-OSA (2024) → the first medicine ever approved for sleep apnoea (December 2024).
  • Phase 2 liver signals → ESSENCE (2025) → FDA, EU and MHRA approvals for MASH (2025–26) → retatrutide’s liver-fat programme.
  • Patient reports of quieted cravings → EHR cohort studies (2024) → randomised trials in alcohol-use disorder (2025–26) → registered follow-on trials.
  • Lean-mass findings → muscle-preserving combination trials (BELIEVE, COURAGE, 2025–26).
  • Withdrawal data → maintenance trials, including TRIUMPH-6 (running).

What this article does not settle

Indication does not mean mechanism: how much of each benefit flows through weight loss itself, and how much through direct receptor effects, is an open research question in every one of these areas. Several headline figures above are topline or press-level rather than journal-published (the TRIUMPH results in particular), several primary papers sit behind journal paywalls and are cited here from their abstracts, and the addiction findings are phase 2 evidence in small samples — signals under active study, not treatments. Nothing here supports self-administration of anything; every result above was produced under clinical supervision inside a licensed trial.

Sources

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