AACE Questions Diabetes Medication-Cancer Link

Insufficient evidence of cancer link seen

There is currently insufficient evidence to support a definitive link between antihyperglycemic medications—such as metformin, insulin, thiazolidinediones (TZDs), GLP-1, and sodium-glucose cotransporter 2 inhibitors (SGLT2)—and cancer development, according to a consensus statement released by the American Association of Clinical Endocrinologists (AACE).

In addition,  while the AACE acknowledges “the importance of clinicians’ consideration of risk factors when making medication choices in individuals identified at risk for cancer, the paper also recommends physicians should continue to confidently prescribe FDA-approved anti-hyperglycemia medications for the treatment of high blood sugar.”

“The implication of various medications’ role in the development of cancer has concerned physicians and patients alike, but the sum of evidence presents a very compelling case and suggests the risk of cancer is unproven,” said Yehuda Handelsman, MD, and co-chair of the consensus statement task force. “Thus, healthcare professionals can have greater confidence in prescribing medications for those who have diabetes or are obese.”

“The research conducted to date is incomplete and, thus, insufficient to warrant withholding treatment that will result in adverse outcomes for those who have diabetes or are obese,” Dr. Handelsman added. “Until more definitive evidence becomes available, the benefits of treatment should take precedence over any concerns for potential low-grade cancer risk.”

The consensus statement was developed by AACE in response to growing concerns in recent years about the possible link between diabetes, obesity, anti-diabetes agents and an increased prevalence of various cancers. The full paper will appear in the September/October issue of Endocrine Practice.

According to a release by AACE, the  task force was commissioned by AACE and the American College of Endocrinology (ACE) and consisted of  international experts who presented the available science, followed by an exhaustive analysis of the evidence, evaluating the possible roles of obesity, hyperinsulinemia, glucose, and diabetes and its therapies in the origin and development of cancer in order to provide practical recommendations to physicians, clinicians and investigators.

Other key conclusions highlighted in the AACE consensus statement include:

• “While there is currently insufficient evidence to suggest glucose-lowering drugs impact cancer development, physicians should exercise caution when prescribing anti-hyperglycemic medications implicated in the promotion of specific cancers (ie, pioglitazone with bladder cancer) to those with elevated cancer risks.”

• “Obesity and diabetes are associated with statistically significant and clinically important increased risks of multiple malignancies. This suggests that cancer screening and counseling on lifestyle changes should be a part of regular preventive care in people with obe­sity and/or diabetes.”

• “Conversely, individuals who develop ‘typical’ obesity-related cancers, especially at a younger age, should be screened for metabolic abnormalities like insulin resistance, metabolic syndrome, diabetes, and cardiovascular disease.”

• Due to the proposed mechanistic association of endogenous hyperinsulinemia with cancer growth, there is a concern that exogenously administered insulin may amplify the cancer development process Although some earlier studies suggested that insulin therapy was associated with a slightly increased risk of cancer incidence, more recent prospective studies (eg, ORIGIN) do not confirm that observation and in fact demonstrate the safety of insulin.

Citing the complex and inconclusive findings addressing the correlation between diabetes, pharmacological therapies, and cancer, larger-scale randomized studies are necessary to advance any plausible evidence linking cancer risks to diabetes, obesity and anti-hyperglycemic medications.

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