---
type: source
title: "Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (JAMA Network Open, 2025)"
author: "JAMA Network Open"
url: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2829779
date: 2025-01-01
domain: health
secondary_domains: []
format: peer-reviewed study
status: unprocessed
priority: high
tags: [glp-1, discontinuation, adherence, obesity, T2D, real-world, JAMA, persistence, weight-regain, reinitiation]
---

## Content

Published in JAMA Network Open (PMC11786232). Large real-world study examining GLP-1 receptor agonist discontinuation patterns among US adults with overweight or obesity.

**Core discontinuation findings:**
- **46.5%** of patients with type 2 diabetes (T2D) discontinued GLP-1 agonists within one year
- **64.8%** of obesity-only patients (without T2D) discontinued within one year
- More than 30% of all patients dropped out within the first 4 weeks (during dose titration phase — when GI side effects are worst)

**Reinitiation patterns:**
- Weight regain following discontinuation strongly predicted reinitiation
- 1% weight increase associated with 2.3% higher likelihood of resuming in T2D patients; 2.8% in non-T2D patients
- The cycle: discontinue → regain weight → reinitiate — creates a revolving-door usage pattern

**Factors predicting discontinuation:**
- History of GI medication: 9% more likely to discontinue
- History of psychiatric medication: 12% more likely to discontinue
- Cardiovascular disease or other chronic conditions: 10% more likely to discontinue
- Age 18-34: more likely to drop out early
- Income >$80K: less likely to discontinue

**Clinical significance:**
- Obesity-indication patients (no T2D) have meaningfully WORSE adherence than T2D patients (64.8% vs 46.5% annual discontinuation)
- The adherence gap by indication has cost implications: CMS coverage, employer coverage decisions, and cost projections all depend on assumed persistence rates
- The titration-phase dropout (>30% in first 4 weeks) suggests drug tolerability, not efficacy, is the primary early barrier

## Agent Notes

**Why this matters:** This is the cleanest peer-reviewed quantification of the T2D vs. obesity adherence gap. The existing KB claim says "GLP-1s chronic use model makes cost impact inflationary through 2035" — but this data suggests the chronic use assumption breaks down at the actual adherence rate. If 65% of obesity-indication patients discontinue within a year, the real-world cost trajectory is significantly lower than models built on trial-level adherence.

**What surprised me:** The 30% dropout in the FIRST 4 WEEKS is striking. The titration phase is the maximum side effect period. This suggests the problem is tolerability during initiation, not long-term commitment — and it's solvable with better initiation support (smaller starting doses, better nausea management protocols).

**What I expected but didn't find:** Data on adherence by insurance type (commercial vs. Medicaid vs. Medicare). The income proxy suggests access costs matter, but the direct insurance-type analysis isn't in this abstract.

**KB connections:**
- Enriches the existing GLP-1 KB claim ("chronic use model inflationary through 2035") — the "chronic use model" assumption is empirically weak; real-world adherence undermines the cost projection
- Connects to HealthVerity 2025 archive (63% year-one persistence for 2024 commercial cohort, 14% at year 3) — the JAMA paper covers a different population slice (clinical T2D vs. commercial weight loss) but directionally consistent
- The income >$80K finding connects to KFF access equity data — financial access barriers predicting both initiation AND persistence
- Connects to digital coaching adherence data (JMIR 2025): the 67% vs 47% gap shows digital programs can close the adherence deficit

**Extraction hints:**
- ENRICH the existing GLP-1 claim with real-world adherence stratification: T2D vs. obesity-only differential is an extractable finding
- The titration-phase 30% dropout is worth flagging as a new mechanism: early tolerability failure as the dominant adherence barrier for obesity patients
- The reinitiation cycle (regain → restart) is a new structural finding — GLP-1s are becoming a "chronic-relapsing" drug category, not a "chronic maintenance" one — economically very different

**Context:** JAMA Network Open is a top-tier open-access peer-reviewed journal. This is a large real-world claims data study, not a clinical trial — it reflects actual prescribing and discontinuation, not protocol-driven behavior.

## Curator Notes (structured handoff for extractor)
PRIMARY CONNECTION: GLP-1 KB claim on "chronic use model inflationary through 2035" — this data challenges the chronic use assumption
WHY ARCHIVED: Peer-reviewed confirmation that real-world adherence is much worse than clinical trials — 65% annual dropout for obesity indication. Enriches and potentially challenges the cost projection framing.
EXTRACTION HINT: Don't extract as standalone claim. Use to QUALIFY/CHALLENGE the existing "inflationary through 2035" GLP-1 claim by adding the adherence caveat: the inflationary projection assumes chronic use that real-world data contradicts. The claim needs a challenged_by annotation referencing this source.
