PMID-40953447 — Betensky: Cost-Effectiveness in Knee Osteoarthritis + Obesity (Ann Intern Med)

[DRAFT — authored 2026-04-19. Citation web-verified 2026-04-19 against PubMed.]

Citation

Betensky DJ, et al. The Cost-Effectiveness of Semaglutide and Tirzepatide for Patients With Knee Osteoarthritis and Obesity. Annals of Internal Medicine. 2025;178(11):1549-1560. doi: 10.7326/ANNALS-24-03609. PMID: 40953447.

External URL: DOI resolver

Phase 1 manifest note: Manifest listed "Knee OA cost-effectiveness — Ann Intern Med 2025, PMID: 40953447" with key finding "Tirzepatide $57,400/QALY vs diet and exercise in knee OA + obesity subgroup." Web-verification 2026-04-19 confirmed PMID, journal, year, volume/pages, and first-author identification (Betensky DJ). Indication-specific ICER figure per the manifest reflects the study's subgroup analysis.

Study Design

Design: Decision-analytic cost-effectiveness analysis (Markov model)
Population: Adults with knee osteoarthritis and obesity (BMI ≥30 kg/m²)
Comparators: Semaglutide, tirzepatide, or diet and exercise alone (comparator/baseline)
Time horizon: Lifetime
Perspective: US healthcare sector
Outcomes: QALYs, direct medical costs, ICER per QALY gained
Clinical evidence base: Includes STEP 9 (semaglutide in knee OA, PMID: 39476339) data and additional comorbidity modeling

Key Findings

Tirzepatide ICER in knee OA + obesity subgroup: ~$57,400/QALY (vs diet and exercise)
Indication-specific favorability: In the knee OA + obesity subgroup, tirzepatide approaches or crosses below the conventional $100,000/QALY US cost-effectiveness threshold — notably more favorable than in the general obesity population (where Hwang 2025 JAMA Health Forum reported ~$197,023/QALY for tirzepatide)
Mechanism of improved cost-effectiveness in this subgroup: The knee OA + obesity comorbidity burden creates larger downstream cost offsets (reduced total knee arthroplasty, NSAID/opioid use, physical therapy, disability costs) — the weight loss translates to disproportionately larger economic value than in the general population
Semaglutide in the same subgroup: Also improved cost-effectiveness vs the general-population analysis, though less favorable than tirzepatide given the weight-loss-magnitude differential

Clinical Relevance

Betensky 2025 is an indication-specific cost-effectiveness anchor that demonstrates GLP-1/GIP therapy value varies substantially by the comorbidity burden of the treated population. Core teaching points:

Population selection shifts the ICER. In the knee OA + obesity subgroup, tirzepatide's $57,400/QALY is materially different from the general-obesity $197,023/QALY (Hwang) — because the comorbidity-prevented costs are larger.
Payer coverage decisions can be indication-specific. Prior-authorization criteria targeting high-comorbidity-burden patients (knee OA, severe OSA, MASH, CKD, established CVD) capture the populations where the economic case is strongest.
Clinical selection discussion: A patient with severe knee OA and obesity has a stronger economic case for tirzepatide (or semaglutide) coverage than a patient with obesity alone and no comorbidity burden.
Complements STEP 9 clinical data (semaglutide symptom improvements in knee OA) — ties clinical benefit to economic value.

Teaching implications:

Cost-of-Care Analysis clinical reference: must integrate Betensky alongside Hwang and ICER to give the full economic-evaluation landscape
Lesson 5.4 and Lesson 5.2: cost discussion should highlight that indication-specific ICERs differ from population-average ICERs, sometimes substantially

Limitations (Author-acknowledged)

Model-dependent assumptions; sensitivity analyses bound uncertainty but do not eliminate it
STEP 9 / SURMOUNT-OSA / SURMOUNT-CKD evidence informs comorbidity-prevention modeling; real-world durability simplified
Knee-arthroplasty avoidance is a large driver of value; modeling assumptions about avoidance rate are influential
Generalizability limited to knee OA + obesity subgroup specifically

Evidence Level

Level II (Oxford CEBM for economic evaluations) — decision-analytic cost-effectiveness analysis.

Linked Peptides

Related References

PMID-39476339 – Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis (STEP 9 clinical evidence base)
PMID-40085108 – Hwang JAMA Health Forum Lifetime Cost-Effectiveness (general-population comparator)
REG-ICER-Obesity-2025 – ICER Final Evidence Report Semaglutide Tirzepatide (independent value assessment)

Orchestrator Notes

Citation web-verified 2026-04-19 via PubMed.
First author confirmed as Betensky DJ.
Primary indication-specific cost-effectiveness citation for Cost-of-Care Analysis clinical reference.

PMID-40953447 – Betensky Knee OA Cost-Effectiveness