Liraglutide 3 mg for Knee Osteoarthritis (LOSEIT)
Osteoarthritis, Obesity
About this trial
This is an interventional treatment trial for Osteoarthritis focused on measuring Liraglutide, Liraglutide 3 mg, Osteoarthritis, Obesity
Eligibility Criteria
Inclusion Criteria:
- Informed consent obtained
- Clinical diagnosis of knee OA (American College of Rheumatology (ACR) criteria) confirmed by radiology but restricted to definite radiographic OA at early to moderate-stages (Kellgren-Lawrence grades 1, 2, or 3)
- Age ≥ 18 years and < 75 years
- Body mass index (BMI) ≥ 27 kg/m2
- Stable body weight during the previous 3 months (< 5 kg self-reported weight change)
- Motivated for weight loss
Exclusion Criteria:
- On-going participation, or participation within the last 3 months, in an organised weight loss programme (or within the last 3 months)
- Current or history of treatment with medications that may cause significant weight gain for at least 3 months before this trial
- Current use or use within three months before this trial of GLP-1 receptor agonist, pramlintide, sibutramine, orlistat, zonisamide, topiramate, or phentermine
- Type 1 diabetes
- Type 2 diabetes treated with glucose-lowering drugs other than metformin
- Alloplasty in target knee joint (see section 6.3)
- End stage disease in target knee joint (Kellgren-Lawrence grade 4)
- Immuno-inflammatory disease
- Chronic wide-spread pain
- Pregnancy or insufficient anti-conception therapy for female fertile patients
- Breast-feeding
- Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x above upper normal range (UNR)
- Surgery scheduled for the trial duration period, except for minor surgical procedures
- Surgical procedures such as arthroscopy or injections into a knee within 3 months prior to enrolment
- Previous surgical treatment for obesity (excluding liposuction >1 year before trial entry)
- Thyroid stimulating hormone (TSH) outside of the range of 0.4-6.0 mIU/L
- Obesity secondary to endocrinologic or eating disorders or to treatment with medicinal products that may cause weight gain
- Family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
- Inflammatory bowel disease
- Congestive heart failure, New York Heart Association (NYHA) class III-IV
- Diabetic gastroparesis
- History of or current diagnosis of pancreatitis (acute and/or chronic) or pancreatic cancer
- History of cancer with the exception of in-situ malignancies of the skin or cervix uteri
- History of major depressive disorder, a PHQ-9 (Patient Health Questionnaire-9) score of more than 15, or a history of other severe psychiatric disorders or diagnosis of an eating disorder
- Subjects with a lifetime history of a suicide attempt or history of any suicidal behaviour within the past month before entry into the trial
- Inability to speak Danish fluently
- A mental state impeding compliance with the program
- Use of opioids or similar strong analgesics
- Allergic reactions to the active ingredients of Saxenda, such as hypotension, palpitations, dyspnoea and oedema
Sites / Locations
- Department of Rheumatology
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Liraglutide 3 mg
Liraglutide 3 mg placebo
Arm description: Subjects will be up titrated to liraglutide 3 mg QD and stay on that dose for the remainder of the 52-week drug intervention period. Drug: Liraglutide 3 mg QD administered in a 6 mg/mL, 3 mL pen for subcutaneous injection. Dose escalation scheme: Initial dosage of 0.6 mg per day, escalated bi-weekly by 0.6 mg to 3 mg per day over a total of 8 weeks.
Arm description: Subjects will be up titrated to liraglutide 3 mg placebo QD and stay on that dose for the remainder of the 52-week drug intervention period. Drug: Liraglutide 3 mg placebo QD administered in a 6 mg/mL drug equivalent volumes, 3 mL pen for subcutaneous injection. Dose escalation scheme: Initial dosage of a 0.6 mg drug equivalent volume per day, escalated bi-weekly by an 0.6 mg drug equivalent volume per day to a 3 mg drug equivalent volume per day over a total of 8 weeks.