US FDA Guidance for Industry on Diabetes Therapies- Revisited

Amidst the continuous development of newer oral anti-diabetic agents, today we are going to revisit a significant guidance draft that was issued by The US Food and Drug Administration (USFDA) on the evaluation of new anti-diabetic drugs.

The guidance titled "Type 2 Diabetes Mellitus (T2DM): Evaluating the Safety of New Drugs for Improving Glycemic Control” was issued by USFDA in 2020 and emphasized on Broader Evaluations Beyond Cardiovascular Outcomes Trials. With this, the draft replaced the outdated requirement that manufacturers conduct cardiovascular outcome trials to rule out unacceptable cardiovascular safety risk.

The move came in the light of the fact that since the earlier released US FDA guidance draft (2008), none of the CVOTs conducted have identified an increased risk of ischemic cardiovascular events. “Some of the CVOTs have instead demonstrated a reduced risk for CV events" the US FDA 2020 draft guidance added.

The FDA draft guidance recommends an updated approach for evaluating the safety profile of anti-hyperglycemic agents. The recommendations include enrolling a broader spectrum of patients with comorbidities and diseases linked to diabetes, including older individuals and those with underlying renal and cardiovascular co-morbidities.

The guidance recommends for following pertaining to:

Size of Safe Database*:

• At least 4,000 patient-years of exposure to the new drug in phase 3 clinical trials
• At least 1,500 patients were exposed to the new drug for at least 1 year
• At least 500 patients were exposed to the new drug for at least 2 years

Patient Characteristics:^**

• At least 500 patients with stage 3/4 chronic kidney disease exposed to the new drug
• At least 600 patients with established CV disease exposed to the new drug
• At least 600 patients aged >65 years were exposed to the new drug
• At least 1,200 patients with at least one of these conditions.

In addition, the guidance details other considerations for the industry to optimize the collection of safety data for glucose-lowering agents.