Liraglutide 3 mg for Knee Osteoarthritis

A randomised, double blind, placebo-controlled, parallel group, and single-centre trial investigating the effect of liraglutide on body weight and pain in overweight or obese patients with knee osteoarthritis.

Patients will be subjected to a run-in diet intervention phase (week -8 to 0) including a low-calorie diet and dietetic counselling. At week 0 patients will be randomised to receive either liraglutide 3 mg or liraglutide 3 mg placebo as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle.


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