In 2008, the Food and Drug Administration required all new anti diabetes medications to prove cardiovascular safety. This landmark decision reshaped therapeutic development. It also produced a wealth of reliable evidence from large clinical trials such as LEADER, SUSTAIN, CANVAS, PIONEER 6, DECLARE TIMI 58, and REWIND. These studies now guide clinicians every day and help protect millions of patients from drug related cardiovascular harm.
The FDA has now released a new draft recommendation that broadens this mandate. It moves beyond the narrow focus on major cardiovascular events and includes safety trials for nephropathy, neuropathy, retinopathy, and sleep apnea. It also reinforces the need to evaluate ischemic atherosclerosis in a more comprehensive way. The agency highlights that these non ASCVD complications can raise mortality risk in type 2 diabetes. Because of this, the FDA believes that modern diabetes drugs must show safety across several organ systems, not only the heart.
This shift signals an evolution in how regulators view diabetes. Type 2 diabetes affects the kidneys, nerves, eyes, and sleep physiology long before heart disease develops. Each complication carries its own risk. Each one can change long term survival. Adding these conditions to the official safety framework will likely push future clinical trials to study broader outcomes, longer timelines, and more diverse patient populations.
The recommendations remain preliminary, yet their impact seems certain. Once finalized, they will reshape anti diabetes clinical research for the next fifteen years. Companies will design trials that monitor renal decline, track neuropathy progression, evaluate retinopathy worsening, and measure sleep apnea severity. Researchers will also refine how they track ischemic atherosclerosis and metabolic risk. This expanded approach will likely improve patient safety and reveal unexpected benefits or weaknesses of emerging medications.
For clinicians and patients, the coming decade may bring more multidimensional data, clearer risk profiles, and safer long term treatment strategies. I will follow these developments closely. Stay tuned.
About Dr. Gerti Tashko, MD
Dr. Gerti Tashko, MD, is an endocrinologist in Montgomery County, Maryland. He is uniquely quadruple board-certified in endocrinology, lipidology, hypertension, and obesity medicine. His practice delivers root-cause-focused metabolic and endocrine care, available virtually and in person. He uses advanced diagnostics, personalized nutrition, and preventive medicine to improve long-term health.
FDA Guidance – Diabetes, Safety Clinical Trials, March 2020
The U.S. Food and Drug Administration today issued a new draft guidance, “Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control,” to solicit public comment on its proposals for broad safety evaluations before drug approval that look beyond ischemic (reduced blood flow) cardiovascular disease, as well as for the inclusion of a broader scope of human subjects, such as older subjects and those with chronic kidney disease who may be more vulnerable to drug-related side effects.
The new draft guidance does not contain the recommendation that sponsors of all new therapies for type 2 diabetes uniformly rule out a specific degree of risk for ischemic cardiovascular adverse outcomes, which was recommended in previous guidance and has typically been done through cardiovascular outcome trials.
“The FDA continues to review new clinical trial evidence and update its recommendations for drug development to reflect emerging scientific information,” said Lisa Yanoff, M.D., acting director of the Division for Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “By following previous FDA recommendations, sponsors have shown that new type 2 diabetes drugs do not have excess ischemic cardiovascular risk, which has provided reassuring cardiovascular safety information for millions of diabetes patients. Now, with this proposed approach, we will have broader, valuable safety information for these medications.”
The 2020 draft guidance stems from the ongoing evaluation of cardiovascular outcomes trials and recommendations from the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee, which noted safety data beyond ischemic cardiovascular safety data was desired to evaluate the safety profile of antidiabetic drugs before they were approved.
More than 30 million Americans have diabetes, and 90-95% of them have type 2 diabetes. People with type 2 diabetes can suffer from serious medical complications, such as nerve damage, kidney and eye damage, sleep apnea, and heart and blood vessel disease, as a result of high glucose (blood sugar) levels in the blood. These patients may also be more likely to die prematurely compared with people without type 2 diabetes.
While a healthy lifestyle may slow or even stop the disease, many patients also take medications to improve glycemic (blood sugar) control. It is important that companies robustly evaluate the medications’ safety in clinical trials to identify risks. This knowledge can help patients and their health care providers make the most informed treatment decisions.
The 2020 draft guidance will replace the FDA guidances for industry, “Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes,” published in December 2008, and “Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and Prevention,” published in February 2008.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.