Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of drugs used in the treatment of type 2 diabetes. Since their release less than 6 years ago, SGLT2 inhibitors have become increasingly popular, as they effectively lower blood sugar levels without the side effects of other antidiabetic drugs. However, there are some concerns that these drugs may increase the risk of fractures. Indeed, in the elderly population, fractures pose a severe health risk, as they are frequently associated with other serious complications and may even lead to death. To date, no observational study has been conducted to determine whether the use of SGLT2 inhibitors is associated with an increased risk of fracture. Thus, using the Clinical Practice Research Datalink, we will assemble a large group of patients with type 2 diabetes to address this important safety question. This study will provide much needed information on the safety of SGLT2 inhibitors, and will be of value to regulatory agencies, physicians, and patients.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of drugs for type 2 diabetes. These drugs work by inhibiting glucose reabsorption in the proximal tubule of the kidneys, increasing urinary glucose output to maintain optimal glycemic levels. While SGLT2 inhibitors are associated with favourable effects, including a low risk of hypoglycemia, there are concerns that these drugs may increase the risk of important adverse events. After reviewing safety data from pre-marketing trials, regulatory agencies expressed concerns that use of SGLT2 inhibitors may increase fracture risk. However, post-marketing trials of SGLT2 inhibitors have produced mixed findings. Although the mechanism supporting an increase in fractures is not entirely understood, it may be explained by elevated serum phosphate levels associated with increased tubular reabsorption, or by a reduction in bone mineral density.
We will assemble a cohort of approximately 80,000 patients newly-treated with antidiabetic drugs between January 1, 2013 and December 31, 2017, with follow-up until March 31, 2018. Current use of SGLT2 inhibitors will be modelled as a time-varying variable. Time-dependent Cox proportional hazards models will be used to estimate hazard ratios with 95% confidence intervals of fractures associated with use of SGLT2 inhibitors, compared with use of dipeptidyl peptidase-4 inhibitors.
Fractures
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Antonios Douros - Collaborator - McGill University
Devin Abrahami - Collaborator - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital