This is a randomized, placebo-controlled study. Patients with long COVID will be randomized to receive dapagliflozin or placebo for 12 months.

This is a multi-centre, randomized, placebo-controlled trial (Figure 4). We will randomly assign patients with long COVID to 12 months of dapagliflozin 10 mg or placebo daily. The 10 mg daily dose of dapagliflozin was used in large clinical trials (44,48) and is the Health Canada approved dose for heart and kidney disease. Additionally, this dose was used in the MRI study of body composition (58) and the RCT in patients with acute COVID-19 (54).

Eligible patients with long COVID will be recruited from post COVID programs or advertisement through-multi-media. A total of 192 participants will be enrolled and this is anticipated to take 3 years. Participants will be followed for the entire duration of the study. Based on a study duration of 5 years (3-year recruitment, 2-year follow-up), patients will be followed for a median of 3.5 years.

Inclusion Criteria:

• 18 years of age or older and willing and able to provide informed consent
• Patients with a history of positive COVID-19 test (polymerase chain reaction or rapid test) or have been diagnosed with COVID-19 by a health care provider.
• New or persistent symptoms at least 12 weeks from infection and present for at least 8 weeks that is not explained by an alternative diagnosis (64).
• Women of childbearing potential (WOCBP) who, if sexually active, are willing to use to use at least one highly effective methods of contraception throughout the study.

Exclusion Criteria:

• History of diabetes
• Prior heart failure
• Weight loss treatment with glucagon-like peptide-1 receptor agonists (e.g. liraglutide, semaglutide)
• Pregnancy or planned pregnancy in the next 12 months. We will ask WOCBP about the possibility of pregnancy at the time of screening and if so, then pregnancy testing will be offered. If testing is declined in this instance, then they will be excluded from the study.
• Women who are breastfeeding
• Severe renal impairment (eGFR<30mL/min1.73m2)
• Known history of allergy or hypersensitivity to dapagliflozin

Exclusion for optional MRI portion of the protocol:

- Any contraindication to MRI