Current partner codePEPTIDESDE
NCT07731256·Phase 2·INTERVENTIONAL

Semaglutide for Low Back Pain

Status

Not yet recruiting

Phase

Phase 2

Enrollment

250

Locations

2

Results

Not posted

Publications

12

Study summary

What the protocol is testing.

Low back pain is the leading cause of disability in the United States, and obesity is a major risk factor for its development. GLP-1 receptor agonists such as Semaglutide have emerged as effective weight loss agents that may also reduce chronic pain through weight reduction and other mechanisms. This randomized, double-blind, placebo-controlled trial will enroll 250 adults with chronic low back pain and obesity, randomized 1:1 to weekly Semaglutide 2.4 mg or placebo for 52 weeks. The primary outcome is change in low back pain severity, with secondary outcomes including pain-related disability and quality of life.

Interventions

Treatment arms and agents.

DRUG

Semaglutide (administered by PDS290 pen-injector)

Semaglutide 3.0 mg/mL solution for subcutaneous injection, administered using a 3 mL PDS290 pen-injector. Administered subcutaneously once weekly on the same day each week, without regard to meals. Dose escalation: 0.24 mg weekly for 28 days, then increased to 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg every 4 weeks to reach the maintenance dose of 2.4 mg. The pen uses a drum scale of 1-80 (in increments of 1); corresponding dose counter values are: 0.24 mg = 8, 0.5 mg = 17, 1.0 mg = 34, 1.7 mg = 57, 2.4 mg = 80. Treatment duration is 52 weeks.

DRUG

Placebo (administered by PDS290 pen-injector)

Matching placebo solution for subcutaneous injection, administered using a 3 mL PDS290 pen-injector. Administered subcutaneously once weekly on the same day each week, without regard to meals, following the same escalating dose counter schedule as the active comparator (counter values: 8, 17, 34, 57, 80 every 4 weeks). Treatment duration is 52 weeks.

Timeline

From registration to results.

  1. First posted

    Jul 28, 2026

  2. Study start

    Feb 1, 2027

  3. Primary completion

    Jan 1, 2031

  4. Study completion

    Sep 1, 2031

  5. Results posted

    Not reported

  6. Registry updated

    Jul 28, 2026

Outcomes

What the study measures.

Primary outcomes

BPI-SF Pain Severity Scale

Time frame · Baseline, up to 52 weeks

The primary endpoint will be change in low back pain severity, measured using the 0-10 BPI-SF Pain Severity Scale. This outcome will be compared in the treatment group versus placebo.

Secondary outcomes

BPI-SF Pain Interference

Time frame · Baseline, up to 52 weeks

Oswestry Disability Index (ODI)

Time frame · Baseline, up to 52 weeks

SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)

Time frame · Baseline, up to 52 weeks

PROMIS Depression

Time frame · Baseline, up to 52 weeks

Pain Catastrophizing Scale

Time frame · Baseline, up to 52 weeks

Insomnia Severity Index

Time frame · Baseline, up to 52 weeks

PROMIS Sleep Disturbance

Time frame · Baseline, up to 52 weeks

Waist Circumference

Time frame · Baseline, up to 52 weeks

Number of New Concomitant Back Pain Treatments

Time frame · Baseline, up to 52 weeks

The number and type of new low back pain treatments initiated during the study period, captured using the study's Concomitant Back Pain Treatment Log. New daily pain medications, exercise/therapy regimens, cognitive/behavioral interventions, spinal injections, interventional pain procedures, lumbar spine surgery, and other treatments.

Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP)

Time frame · Baseline, every 6 months till 52 weeks.

Serum hs-CRP will be measured at each time point and reported in mg/L. Additional exploratory inflammatory blood biomarkers may also be assessed to characterize systemic inflammation.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
85 Years
Sex
ALL
Healthy volunteers
No

Inclusion Criteria: * Ability to provide informed consent before any trial-related activities * Age: 18-85 years * Chronic low back pain, defined as an average low back pain severity of at least 4/10 present on most days for 3 months or longer. * BMI: 30-49 kg/m2 Exclusion Criteria: * Known or suspected allergy to trial medication(s), excipients, or related products * Contraindications to study medication(s), worded specifically as stated in the product's Prescribing Information * Previous randomization in this trial * Pregnant, breastfeeding, or the intention of becoming pregnant or not using adequate contraceptive measures * Low back pain related to infection, trauma, or malignancy * Plans to undergo new back pain interventions within 3 months. * Considering or have been offered surgery to treat structural disease believed to cause their low back pain, including infection, severe degeneration adjacent to a prior fusion, mobile spondylolisthesis, severe central lumbar stenosis, coronal or sagittal deformity, or other severe structural pathology diagnosed by a board-certified spine surgeon. Ambiguous cases will be adjudicated by a board-certified spine surgeon. * Another source of pain that is more severe than their low back pain (e.g., headache or radiculopathy) * History of or plans to undergo bariatric weight loss surgery * History of a major abdominal or stomach surgery that might affect drug absorption * Decrease in body weight of \> 5 kg within 3 months of screening * History of diabetes mellitus, with HbA1c \> 7 or requiring medical treatment (i.e., insulin or other diabetes medication other than Metformin). * Uncontrolled hypertension, defined as a systolic blood pressure (BP) \> 155 mmHg or a diastolic BP \> 100 mmHg * Clinically significant congestive heart failure, defined as New York Heart Association Class IV, or active symptoms related to heart failure, or exacerbation requiring hospitalization within 90 days of screening. * Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris, or transient ischemic attack within 90 days of screening. * Other medical conditions that could impact their treatment, similar to prior published reports * Treatment with oral or injectable glucagon-like peptide-1 (GLP-1) receptor agonists within 3 months before screening * Active acute or chronic pancreatitis diagnosed within 180 days or history of unprovoked pancreatitis within the past year. * Stage 3 or worse chronic kidney disease (i.e., eGFR \< 60). * Known active gallstone disease, other than disease previously treated with cholecystectomy. * Newly diagnosed or worsening chronic liver disease. * Active malignancy * Major neurological disease, such as multiple sclerosis or Parkinson's Disease * Major psychiatric disease, such as psychosis or schizophrenia, or a psychiatric disease requiring hospitalization in the preceding 12 months * History of a suicide attempt or any reported suicidal behavior reported within 30 days of screening. * Personal history of MEN2 * Personal or family history of medullary thyroid cancer * Impaired sensorium due to alcohol or drug use.

Study locations

2 registered sites.

United States. Showing up to 24 locations stored in the fast local snapshot.

The University of Alabama at Birmingham

Birmingham, Alabama, United States

Washington University School of Medicine

St Louis, Missouri, United States

Publications

Results and literature.

PMID 32520773Smith SM, Dworkin RH, Turk DC, McDermott MP, Eccleston C, Farrar JT, Rowbotham MC, Bhagwagar Z, Burke LB, Cowan P, Ellenberg SS, Evans SR, Freeman RL, Garrison LP, Iyengar S, Jadad A, Jensen MP, Junor R, Kamp C, Katz NP, Kesslak JP, Kopecky EA, Lissin D, Markman JD, Mease PJ, O'Connor AB, Patel KV, Raja SN, Sampaio C, Schoenfeld D, Singh J, Steigerwald I, Strand V, Tive LA, Tobias J, Wasan AD, Wilson HD. Interpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerations. Pain. 2020 Nov;161(11):2446-2461. doi: 10.1097/j.pain.0000000000001952.PMID 34051018van Lennep JHPA, Trossel F, Perez RSGM, Otten RHJ, van Middendorp H, Evers AWM, Szadek KM. Placebo effects in low back pain: A systematic review and meta-analysis of the literature. Eur J Pain. 2021 Oct;25(9):1876-1897. doi: 10.1002/ejp.1811. Epub 2021 Jun 21.PMID 37385275Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023 Aug 19;402(10402):613-626. doi: 10.1016/S0140-6736(23)01200-X. Epub 2023 Jun 26.PMID 28192789Qaseem A, Wilt TJ, McLean RM, Forciea MA; Clinical Guidelines Committee of the American College of Physicians; Denberg TD, Barry MJ, Boyd C, Chow RD, Fitterman N, Harris RP, Humphrey LL, Vijan S. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Apr 4;166(7):514-530. doi: 10.7326/M16-2367. Epub 2017 Feb 14.PMID 35507483Chiarotto A, Koes BW. Nonspecific Low Back Pain. N Engl J Med. 2022 May 5;386(18):1732-1740. doi: 10.1056/NEJMcp2032396. No abstract available.PMID 8080219Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.PMID 40016636He Y, Xu B, Zhang M, Chen D, Wu S, Gao J, Liu Y, Zhang Z, Kuang J, Fang Q. Advances in GLP-1 receptor agonists for pain treatment and their future potential. J Headache Pain. 2025 Feb 27;26(1):46. doi: 10.1186/s10194-025-01979-4.PMID 39301951Samajdar SS, Bhaduri G, Ghoshal PK, Mukherjee S, Pal J, Chatterjee N, Joshi SR. Dual effects of dulaglutide on glycemic control and knee osteoarthritis pain in elderly patients with Type 2 diabetes. Pain Manag. 2024;14(7):365-373. doi: 10.1080/17581869.2024.2402214. Epub 2024 Sep 20.PMID 39808758Emmerich SD, Fryar CD, Stierman B, Ogden CL. Obesity and Severe Obesity Prevalence in Adults: United States, August 2021-August 2023. NCHS Data Brief. 2024 Sep;(508):10.15620/cdc/159281. doi: 10.15620/cdc/159281.PMID 20007994Shiri R, Karppinen J, Leino-Arjas P, Solovieva S, Viikari-Juntura E. The association between obesity and low back pain: a meta-analysis. Am J Epidemiol. 2010 Jan 15;171(2):135-54. doi: 10.1093/aje/kwp356. Epub 2009 Dec 11.PMID 27537761Jackson T, Thomas S, Stabile V, Shotwell M, Han X, McQueen K. A Systematic Review and Meta-Analysis of the Global Burden of Chronic Pain Without Clear Etiology in Low- and Middle-Income Countries: Trends in Heterogeneous Data and a Proposal for New Assessment Methods. Anesth Analg. 2016 Sep;123(3):739-48. doi: 10.1213/ANE.0000000000001389.PMID 39833406Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med. 2025 Mar;31(3):951-962. doi: 10.1038/s41591-024-03412-w. Epub 2025 Jan 20.

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