Impact
Postauthorization studies in the U.S. and Europe demonstrate the long-term safety of dapagliflozin
An estimated 38.4 million people in the United States and 61 million adults in Europe are living with diabetes. Medications that help them control their glucose levels are essential for managing their condition, so understanding the safety of these widely used treatments is critical for patients, health care providers, and regulatory agencies.
Although clinical trials are rigorous, they often span relatively short timeframes. Because of this, after a drug has been approved, regulatory agencies may require additional monitoring in the form of postauthorization safety studies to investigate the drug’s long-term safety in real-world users.
When a new sodium-glucose cotransporter 2 inhibitor, known as dapagliflozin, was undergoing clinical trials for the treatment of type 2 diabetes, researchers noted early signs of potential liver and kidney injury, as well as increased susceptibility to severe complications of urinary tract infections. Upon approving the drug, the European Medicines Agency (EMA) required the manufacturer to conduct postauthorization safety studies for further investigation into these potential side effects.
A decade-long search for signs of potential liver and kidney injury
From 2012-2022, RTI Health Solutions provided support to the sponsor with regulatory interactions, developed the three study protocols which were endorsed by EMA and included in the Risk Management Plan for dapagliflozin, and coordinated and conducted the postauthorization safety studies in Europe and the U.S. in patients with type 2 diabetes with an external research partner.
The studies used three population-based databases in two countries:
- Clinical Practice Research Datalink (CPRD), a primary care electronic health records database in the United Kingdom.
- Healthcare Integrated Research Database (HIRD), a healthcare administrative claims database of commercially insured individuals in the U.S.
- Medicare, a federally funded fee-for-service insurance claims database in the U.S.
The studies monitored uptake of the medication over time, described patterns of medication use, and performed comparative analyses to estimate the risk of each of the safety outcomes among new users of dapagliflozin compared to new users of other glucose-lowering drugs used to treat type 2 diabetes. These large studies included over 30,000 person-years of real-world dapagliflozin exposure.
Demonstrating the safety and unexpected benefits of dapagliflozin
We found that there is no increased risk of acute kidney injury, acute liver injury, or severe complications of urinary tract infection in people taking dapagliflozin. In fact, compared to other glucose-lowering medications, people taking dapagliflozin experienced lower rates of acute kidney injury. Together with evidence from clinical trials on dapagliflozin, these findings contributed to the removal of these conditions as important identified risks in the dapagliflozin risk-management plan in Europe.
The number of cases and the mortality rate of type 2 diabetes are increasing worldwide. Understanding the safety of diabetes medications in both the short and long term is crucial to managing this condition on an individual and global scale.
Learn more about RTI Health Solutions.
