Diabetes Drug Improves Orthopedic Oncological Outcomes!?
A first-line treatment for diabetes, Metformin, has been shown to extend survival time in patients with carcinomas and may well prove to be a welcome addition to the orthopedic oncological armamentarium, according to a new study titled, “Is Metformin Use Associated With Prolonged Overall Survival In Patients with Soft Tissue Sarcoma? A Surveillance, Epidemiology, and End Results-Medicare Study” published in the November 12, 2021, edition of Clinical Orthopaedics and Related Research.
According to the lead study investigator, Matthew DiCaprio, M.D. a musculoskeletal oncologist with the Division of Orthopaedic Surgery, Albany Medical Center in New York, there are 3,600 bone sarcomas and 13,400 related soft tissue sarcomas diagnosed in the U.S. each year. The incidence of soft tissue sarcomas of the extremities is 3x that of the incidence of bone sarcomas per year.
Metformin, sold under the brand name Glucophage among others, is a first-line treatment for type 2 diabetes, particularly in overweight people. It is also used in the treatment of polycystic ovary syndrome.
Metformin is generally well tolerated. Common adverse effects include diarrhea, nausea, and abdominal pain. It has a low risk of causing low blood sugar. High blood lactic acid level is a concern if the medication is used in overly large doses or prescribed in people with severe kidney problems. It is not recommended in those with significant liver disease.
OTW asked Dr. DiCaprio why he landed on Metformin as a research target. “The father of one of my Ewing’s sarcoma patients alerted me to the benefits observed in other cancer types, primarily carcinomas, in patients who had been taking Metformin. This prompted me to look into the presumed mechanism of action for an anti-cancer benefit and hypothesize that a similar survival benefit would be seen for patients with a soft tissue sarcoma.”
As a result, said Dr. DiCaprio, “The vast majority of soft tissue sarcomas are cared for by orthopedic oncologists. After an orthopedic residency, surgeons do a one-year fellowship in orthopedic oncology to learn how to care for all musculoskeletal tumors, including soft tissue sarcomas.”
DiCaprio and his research group used the Surveillance, Epidemiology, and End Results registry, which is linked to Medicare claims data to pull together a dataset of all patients who had been diagnosed with soft tissue sarcoma from 2007 to 2016. Of the 14,650 patients, 4,844 patients were excluded due to multiple malignancies. Also excluded were patients with multiple sarcomas or diagnosis at autopsy, resulting in a cohort of 9,000 patients.
Of the resulting 9,000 patients in the study, 4,780 had complete, linked datasets (Medicare); 4,606 patients were chosen for the final analysis. The researchers found that 13% of those patients were treated with Metformin in the six months before their sarcoma diagnosis. Comparison groups were as follows: those not taking Metformin (87%), patients with diabetes who did not take Metformin (14%), and patients without a diagnosis of diabetes who were not taking Metformin (73%).
“We found that patients taking Metformin had a survival advantage over those not taking Metformin,” said Dr. DiCaprio to OTW. “Use of Metformin may also enhance response to radiation treatments commonly employed for treatment of soft tissue sarcomas.”
“Our research found that patients treated for soft tissue sarcoma while taking Metformin had modestly prolonged survival compared with their counterparts who did not take Metformin, irrespective of diabetes status. This finding supports the consideration of further studies assessing Metformin as a noncytotoxic adjuvant agent in patients with soft tissue sarcomas. Ultimately, a well-designed, multi-institutional, randomized controlled trial of the effect of Metformin on patients with soft tissue sarcomas may be considered.”