The main purpose of the project is to evaluate the safety and efficacy of low dose metformin for improving symptoms associated with fibromyalgia syndrome (FMS) via modulating neuroinflammatory pathways. The investigators hypothesize that FMS patients in the low-dose metformin conditions will show greater improvement in FMS symptoms than those who are in the placebo group. Further, the investigators hypothesize that metformin will increase phosphorylated AMPK in peripheral immune cells of FMS patients and will decrease the transcription of mTORC1, NLRP3 inflammasome, and nociceptive cytokines interleukin 1beta and interleukin 18.

Fibromyalgia syndrome (FMS) is a chronic pain condition that is debilitating to an estimated 10 million Americans and results in high utilization of medical resources with a cost of over $100 billion in health care and lost productivity each year. It is widely accepted that chronic widespread pain is a defining feature of FMS and that it is maintained by central sensitization. Accumulating evidence demonstrates that central sensitization is driven, at least in part, by neuroinflammation. Thus, molecules that ameliorate the causes of neuroinflammation are intriguing candidates to treat FMS symptoms. Current therapies are only partially effective in about 50% of patients. The development of a treatment approach with better efficacy is urgently needed.

The investigators propose to test the use of metformin for FMS. This drug is widely used as a first line treatment for type II diabetes. Metformin causes the phosphorylation of AMP-activated protein kinase (AMPK), which regulates key enzymes and transcription factors that modulate gene expression involved in metabolism and inflammation. Because AMPK acts as a master switch kinase, this target may prove particularly effective in treating the many diverse symptoms of FMS. Indeed, metformin treated hyperalgesia in preclinical models of neuropathic, inflammatory, spinal cord injury and diabetes-induced mechanical hyperalgesia and reduced symptoms of anxiety, depression and cognitive dysfunction. This is of significant relevance because these symptoms contribute greatly to FMS patient disability.

The investigators expect that this study will determine the effectiveness of metformin on pain and comorbidity FMS symptoms and delineate the role that AMPK and its downstream targets play on these phenotypes. The investigators anticipate that these results will demonstrate the efficacy of an intervention not currently used clinically to treat FMS. Understanding these pathways represents a critical step in the development of non-addictive pain treatments and holds enormous potential to reduce disability in the 10 million Americans with FMS.

Inclusion Criteria:

• To be able to follow the protocol in English
• Fibromyalgia Syndrome: Participant must meet the American College of Rheumatology 2016 revised classification criteria for Fibromyalgia
• Ability to take oral medication and be willing to adhere to the metformin regimen (once daily)

Exclusion Criteria:

• Co-occurring progressive disease (self-report, physician-diagnosed)
• Diabetes
• Pregnancy or planning to be pregnant in the next year (all premenopausal participants will be tested)
• Having known cardiovascular, liver, kidney or pulmonary diseases (self-report, physician-diagnosed)
• Having known serious psychopathology (Clinician diagnoses of psychosis, organic mental disorder, or dissociative disorder, self-reported active suicidal intent, self-reported history of inpatient admission to a psychiatric ward in the past year, evidence or self-report of self-injurious behaviors in the past year, reported current or recent history (2years) of non-IV substance abuse, any history of recreational IV drug use)
• Having autoimmune disorder (e.g., rheumatoid arthritis) (self-report, physician-diagnosed)
• Having neuropathic pain (self-report, physician-diagnosed)
• Having pain associated with a terminal illness, acute pain, pain associated with specific organ damage (eg, stomach ulcer) (self-report, physician-diagnosed)
• Concurrent use of weight controlling medications (eg, Xenical)
• Requiring an interpreter to communicate
• Abnormal levels of creatinine, vitamin B12, or hepatic function panel
• eGFR of below 45mL/min/1.73m2