---
type: claim
domain: health
description: "Two-year real-world data shows only 15% of non-diabetic obesity patients remain on GLP-1s, meaning most patients discontinue before downstream health benefits can materialize to offset drug costs"
confidence: likely
source: "Journal of Managed Care & Specialty Pharmacy, Real-world Persistence and Adherence to GLP-1 RAs Among Obese Commercially Insured Adults Without Diabetes, 2024-08-01"
created: 2026-03-11
depends_on: ["GLP-1 receptor agonists are the largest therapeutic category launch in pharmaceutical history but their chronic use model makes the net cost impact inflationary through 2035"]
---

# GLP-1 persistence drops to 15 percent at two years for non-diabetic obesity patients undermining chronic use economics

Real-world claims data from 125,474 commercially insured patients initiating GLP-1 receptor agonists for obesity (without type 2 diabetes) reveals a persistence curve that fundamentally challenges the economic model: 46.3% remain on treatment at 180 days, 32.3% at one year, and approximately 15% at two years.

This creates a paradox for payer economics. The "chronic use inflation" concern assumes patients stay on GLP-1s indefinitely at $2,940+ annually. But the actual problem may be insufficient persistence: under capitation, a Medicare Advantage plan pays for 12 months of GLP-1 therapy for a patient who discontinues and regains weight—net cost with no downstream savings from avoided complications.

The economics only work if adherence is sustained AND the payer captures downstream benefits. With 85% of non-diabetic patients discontinuing by two years, the downstream cardiovascular and metabolic savings that justify the cost never materialize for most patients.

## Evidence

**Persistence rates for non-diabetic obesity patients:**
- 180 days: 46.3%
- 1 year: 32.3%
- 2 years: ~15%

**Comparison with diabetic patients:**
- Non-diabetic patients: 67.7% discontinue within 1 year
- Diabetic patients: 46.5% discontinue within 1 year (better persistence due to stronger clinical indication)
- Danish registry data: 21.2% of T2D patients discontinue within 12 months; ~70% discontinue within 2 years

**Drug-specific variation:**
- Semaglutide: 47.1% persistence at 1 year (highest)
- Liraglutide: 19.2% persistence at 1 year (lowest)
- Formulation matters: oral formulations may improve adherence by removing injection barrier

**Key discontinuation factors:**
- Insufficient weight loss (clinical disappointment)
- Income level (lower income → higher discontinuation, suggesting affordability/access barriers)
- Adverse events (primarily GI side effects)
- Insurance coverage changes

**Critical nuance from source:** "Outcomes approach trial-level results when focusing on highly adherent patients. The adherence problem is not that the drugs don't work—it's that most patients don't stay on them."

## Challenges

This data comes from commercially insured populations (younger, fewer comorbidities than Medicare). Medicare populations may show different persistence patterns due to higher disease burden and stronger clinical indications. However, Medicare patients also face higher cost-sharing barriers, which could worsen adherence.

No data yet on whether payment model affects persistence—does being in an MA plan with care coordination improve adherence vs. fee-for-service? This is directly relevant to value-based care design.


### Additional Evidence (extend)
*Source: 2025-11-06-trump-novo-lilly-glp1-price-deals-medicare | Added: 2026-03-16*

The $50/month out-of-pocket maximum for Medicare beneficiaries (starting April 2026 for tirzepatide) removes most financial barriers to persistence for the eligible population. Lower-income patients show higher discontinuation rates, suggesting affordability drives persistence. The OOP cap may improve persistence rates specifically in Medicare, though this remains untested.


### Additional Evidence (extend)
*Source: 2025-07-01-sarcopenia-glp1-muscle-loss-elderly-risk | Added: 2026-03-16*

The discontinuation problem is worse than just lost metabolic benefits - it creates a body composition trap. Patients who discontinue lose 15-40% of weight as lean mass during treatment, then regain weight preferentially as fat without muscle recovery. This means the most common outcome (discontinuation) leaves patients with WORSE body composition than baseline: same or higher fat, less muscle, higher disability risk. Weight cycling on GLP-1s is not neutral - it's actively harmful.


### Additional Evidence (extend)
*Source: 2025-01-01-jmir-digital-engagement-glp1-weight-loss-outcomes | Added: 2026-03-16*

Digital behavioral support may partially solve the persistence problem: UK study showed 11.53% weight loss with engagement vs 8% without at 5 months, suggesting the adherence paradox has a behavioral solution component. However, high withdrawal rates in non-engaged groups suggest this requires active participation, not passive app access.


### Additional Evidence (extend)
*Source: 2026-02-01-cms-balance-model-details-rfa-design | Added: 2026-03-16*

BALANCE Model's manufacturer-funded lifestyle support requirement directly addresses the persistence problem by mandating evidence-based programs for GI side effects, nutrition, and physical activity—the factors most associated with discontinuation. This shifts the cost of adherence support from payers to manufacturers.


### Additional Evidence (extend)
*Source: 2025-12-01-who-glp1-guidelines-behavioral-therapy-combination | Added: 2026-03-18*

WHO's conditional recommendation requiring behavioral therapy combination provides international regulatory support for adherence interventions. The guideline explicitly states GLP-1s should be 'combined with intensive behavioral therapy to maximize and sustain benefits'—directly addressing the persistence problem by making behavioral support the standard of care rather than an optional add-on.


### Additional Evidence (extend)
*Source: 2026-03-01-glp1-lifestyle-modification-efficacy-combined-approach | Added: 2026-03-18*

Weight regain data shows that even among patients who complete treatment, GLP-1 alone produces 8.7 kg regain (vs 7.6 kg placebo) while GLP-1 + exercise produces only 3.5 kg regain. This means low persistence may be economically rational for patients if the medication alone doesn't create lasting value—the 15% two-year persistence rate may reflect patients discovering that medication without lifestyle change produces temporary results.


### Additional Evidence (extend)
*Source: 2026-01-13-aon-glp1-employer-cost-savings-cancer-reduction | Added: 2026-03-18*

Aon data shows the 80%+ adherent cohort captures dramatically stronger cost reductions (9 percentage points lower for diabetes, 7 points for weight loss), confirming that adherence is the binding variable for economic viability. The adherence-dependent savings pattern means low persistence rates eliminate cost-effectiveness even when clinical benefits exist.


### Additional Evidence (extend)
*Source: 2026-03-19-vida-ai-biology-acceleration-healthspan-constraint | Added: 2026-03-19*

GLP-1 behavioral adherence failures demonstrate that even breakthrough pharmacology cannot overcome behavioral determinants: patients on GLP-1 alone show same weight regain as placebo without behavior change. This is direct evidence that the 'human constraints' factor (Amodei framework) limits pharmaceutical efficacy independent of drug quality.


### Additional Evidence (extend)
*Source: [[2026-03-01-glp1-lifestyle-modification-efficacy-combined-approach]] | Added: 2026-03-19*

Weight regain data shows GLP-1 alone (8.7 kg regain) performs no better than placebo (7.6 kg) after discontinuation, while combination with exercise reduces regain to 3.5 kg. This suggests the low persistence rates may be economically rational from a patient perspective if medication alone provides no durable benefit—patients who discontinue without establishing exercise habits return to baseline regardless of medication duration.

---

Relevant Notes:
- [[GLP-1 receptor agonists are the largest therapeutic category launch in pharmaceutical history but their chronic use model makes the net cost impact inflationary through 2035]]
- [[value-based care transitions stall at the payment boundary because 60 percent of payments touch value metrics but only 14 percent bear full risk]]
- [[medical care explains only 10-20 percent of health outcomes because behavioral social and genetic factors dominate as four independent methodologies confirm]]

Topics:
- domains/health/_map