health-economics-adherence

Semaglutide MARKETED

health-economics-adherence Not directional

Low evidence

In a real-world US commercially insured cohort of obese adults WITHOUT diabetes newly initiating GLP-1 therapy for weight loss, only 32.3% remained persistent at 1...

Gleason PP, Urick BY, Marshall LZ, Friedlander N, Qiu Y, Leslie RS. Real-world persistenc... Source

Full findingIn a real-world US commercially insured cohort of obese adults WITHOUT diabetes newly initiating GLP-1 therapy for weight loss, only 32.3% remained persistent at 1 year and only 27.2% were adherent (PDC>=80%) - far below the >85% adherence reported in pivotal obesity trials. (Note: this is the diabetes-free obesity stratum, which persists worse than type 2 diabetes; cf. ADHERENCE-02.)

PopulationRetrospective cohort, Prime Therapeutics integrated pharmacy + medical claims (~16.5M monthly commercially insured members); 4,066 obese adults WITHOUT type 2 diabetes initiating GLP-1 in 2021; mean age 46, 81% female; obesity (weight-loss) indication; USA.

Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)

Scope limitspossible confounding by indication

Tirzepatide|semaglutide (head-to-head) MARKETED

health-economics-adherence Not directional

Low evidence

In the largest US real-world EHR cohort, MOST patients with overweight/obesity discontinued GLP-1 RA within 1 year, with discontinuation substantially higher in...

Rodriguez PJ, Zhang V, Gratzl S, Do D, Goodwin Cartwright B, Baker C, Gluckman TJ, Stucky... Source

Full findingIn the largest US real-world EHR cohort, MOST patients with overweight/obesity discontinued GLP-1 RA within 1 year, with discontinuation substantially higher in obesity-without-diabetes (64.8%) than in type 2 diabetes (46.5%); discontinuation was associated with cost/coverage proxies (income) and GI adverse events, while greater weight loss protected against stopping.

PopulationRetrospective cohort, Truveta EHR (collective of US health systems); 125,474 adults (BMI>=27) newly initiating liraglutide, semaglutide or tirzepatide 2018-2023; mean age 54.4, 65.4% women; 61.0% with T2D; obesity vs T2D strata; followed up to 2 yr; USA.

Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)

Scope limitsdisproportionality: reporting != incidence/causality

Semaglutide MARKETED

health-economics-adherence Not directional

Low evidence

In a nationwide T2D real-world database, adherence and persistence to GLP-1 RA were significantly higher for once-weekly than daily formulations and were...

Kassem S, Khalaila B, Stein N, Saliba W, Zaina A. Efficacy, adherence and persistence of ... Source

Full findingIn a nationwide T2D real-world database, adherence and persistence to GLP-1 RA were significantly higher for once-weekly than daily formulations and were socio-economically patterned (better adherence with higher socio-economic status), showing real-world persistence varies markedly by agent/dosing schedule and by access, even within type 2 diabetes.

PopulationRetrospective cohort, Clalit Health Services EMR (Israel, nationwide HMO); 70,654 adults with T2D purchasing any GLP-1 RA 2009-2021; 51% female; T2D indication.

Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)

Scope limitspossible confounding by indication

Comparatorsonce-weekly vs daily GLP-1 RA

Semaglutide MARKETED

health-economics-adherence Not directional

Low evidence

In a MANUFACTURER-SPONSORED (Novo Nordisk) Markov cost-effectiveness model of semaglutide 2.4 mg in the SELECT population (overweight/obese with established CV...

McEwan P, Bog M, Faurby M, Foos V, Lingvay I, Lubker C, Miller R, Toliver JC, Yeates F, L... Source

Full findingIn a MANUFACTURER-SPONSORED (Novo Nordisk) Markov cost-effectiveness model of semaglutide 2.4 mg in the SELECT population (overweight/obese with established CV disease, no diabetes), semaglutide was reported cost-effective at US list price against a $150,000/QALY willingness-to-pay threshold. Context-only economic observation; the headline result is highly price-assumption-dependent and sponsor-authored, so it is paired here with the independent competing null.

PopulationCohort-level Markov state-transition cost-effectiveness model; simulated 100,000 subjects aligned to SELECT (NCT03574597) baseline; healthcare-sector perspective; USA; sponsor Novo Nordisk (four of ten authors Novo employees, others Novo-commissioned HEOR Ltd).

Fundingindustry - Novo Nordisk (sponsor-authored cost-effectiveness model; COI-flagged per Constitution 1.8)

Scope limitsWI-3 NEW-GATHER (cost-effectiveness / QALY, CV-disease obesity setting). Context-only modelling study, not an efficacy/mechanism claim or recommendation. GRADE low by rule (cost-effectiveness model). COI / sponsor-authorship flag (Constitution 1.8): sponsor (Novo Nordisk) authored, advancing the sponsor-favourable 'cost-effective at list price' conclusion - down-weighted at point of use and deliberately paired with the INDEPENDENT competing null (C-TIRZEPATIDE-HEALTHECON-CEA-01, academic, which finds semaglutide NOT cost-effective at net price, ICER $467,676/QALY in the general-obesity setting). The two are not in direct contradiction (different populations: SELECT CV-disease cohort with modelled CV-event savings vs general obesity; different WTP thresholds $150k vs $100k; list vs net price) - record both poles and the price-assumption dependence per Constitution 1.10. scope_limits: model assumptions, list-price sensitivity (rebate scenario swings the ICER ~4x), sponsor COI, generalisability of SELECT to broader population (authors' own caveat).

Comparatorsplacebo; standard of care

Tirzepatide MARKETED

health-economics-adherence Not directional

Low evidence

In an INDEPENDENT (non-manufacturer) US lifetime microsimulation, tirzepatide and semaglutide added to lifestyle modification produced the largest QALY gains among...

Hwang JH, Laiteerapong N, Huang ES, Kim DD. Lifetime Health Effects and Cost-Effectivenes... Source

Full findingIn an INDEPENDENT (non-manufacturer) US lifetime microsimulation, tirzepatide and semaglutide added to lifestyle modification produced the largest QALY gains among anti-obesity medications yet were NOT cost-effective at current US net prices: at a $100,000/QALY threshold both had a 0% probability of being cost-effective across the examined range. Context-only economic observation; not an efficacy or value verdict.

PopulationLifetime cost-effectiveness analysis - individual-level microsimulation (validated Diabetes-Obesity-Cardiovascular Disease microsimulation model) parameterised from NHANES 2017-2020 survey data (4,823 individuals representing ~126M US adults meeting trial inclusion criteria); academic authors (University of Chicago); USA.

Fundingacademic/independent (University of Chicago authors; non-manufacturer; per-paper COI statement not individually audited)

Scope limitsWI-3 NEW-GATHER (cost-effectiveness / QALY anchor for the obesity setting). Context-only: this is a MODELLING study of economic value at a given price, NOT a clinical efficacy or mechanism claim and NOT a recommendation. GRADE low by rule (cost-effectiveness microsimulation is a derived/simulation design with no dedicated rubric tier, so it floors to low - the conservative unparseable-design fallback; correct grade regardless). scope_limits: model assumptions, list/net-price sensitivity, discontinuation-rate assumptions, generalisability of trial inputs to the modelled population. Independent (academic, non-manufacturer) - useful as the competing null against industry-sponsored CEAs that report favourable ICERs (cf. C-SEMAGLUTIDE-HEALTHECON-CEA-01, Novo-sponsored). The two together flag the literature spread: at LIST price reta-class obesity drugs sit well above the $100k/QALY threshold; favourable ICERs depend on rebate/price assumptions. No retatrutide CEA found (not marketed); the price-sensitivity logic would apply a fortiori to a more potent, presumably costlier agent - expectation, not data. [WI-3 independent audit 2026-06-24: source design relabelled from 'observational cohort' to 'cost-effectiveness microsimulation model' and the population text de-laundered (the words 'COHORT'/'observational survey cohort' that had steered the deterministic detector to 'observational cohort' were removed; the study is a microsimulation, not a cohort study). Grade is low either way - the prior text reached low by tripping the cohort detector, the corrected text reaches low as the unparseable-simulation fallback - so this restores accurate text without changing the (correct) grade. The 'confounding by indication' scope_limit, an artefact of the cohort mislabel, was removed; a simulation has no confounding by indication.]

Comparatorssemaglutide; naltrexone-bupropion; phentermine-topiramate; lifestyle modification

Tirzepatide MARKETED

health-economics-adherence Not directional

Low evidence

In two large US claims/EHR databases, most adults WITHOUT type 2 diabetes who initiated tirzepatide were still persistent at 6 months - a higher 6-month persistence...

Gibble TH, Hankosky ER, Meeks A, Liao B, Ward J, Huang A, Chinthammit C. Characteristics ... Source

Full findingIn two large US claims/EHR databases, most adults WITHOUT type 2 diabetes who initiated tirzepatide were still persistent at 6 months - a higher 6-month persistence than has typically been reported for older GLP-1 receptor agonists. Context-only real-world utilisation observation; short follow-up, not comparable to the 1-year discontinuation anchor.

PopulationRetrospective observational claims/EHR cohort, Merative MarketScan Commercial + Optum Clinformatics (CDM); adults without T2D initiating tirzepatide May 2021-Sep 2023; USA; sponsor Eli Lilly.

Fundingindustry - Eli Lilly (sponsor-authored real-world claims study; COI-flagged per Constitution 1.8)

Scope limitspossible confounding by indication; short duration

Most represented records

Evidence spread