SGLT-2 inhibitors are a new class of antidiabetic drugs that have been shown to reduce blood glucose levels and decrease heart attacks. The US Food and Drug Administration recently added warnings to the labels of SGLT-2 inhibitors alerting physicians and patients to an increased risk of genital and urinary tract infections. The biological mechanism responsible for these infections suggests that they may also increase the risk of pneumonia (a common type of infection in the lungs). Given the clinical consequences of pneumonia and the increasing use of SGLT-2 inhibitors, there is an urgent need to examine this drug safety question. To do this, we will compare the number of patients with pneumonia among patients prescribed an SGLT-2 inhibitor to that in patients prescribed a DPP-4 inhibitor (another type of antidiabetic drug), using data from the Clinical Practice Research Datalink (or CPRD) linked to hospitalization data. We will also compare the risk of hospitalization for pneumonia and risk of pneumonia by individual SGLT-2 drug, by duration of use, dose, by a history of respiratory disease, and by age.
Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are a novel class of antidiabetic drugs. While these drugs achieve their benefits by inhibiting SGLT-2, they also have variable affinities for sodium-glucose co-transporter 1 (SGLT-1) that is found in the lung. SGLT-1 inhibition in rat alveolar cells has been shown to increase surface liquid glucose concentration, which translates directly to increased proliferation of pathogenic bacteria. This mechanism is analogous to that behind their increased risk of genital and urinary tract infections with SGLT-2 inhibitors. However, to our knowledge, no study has examined the risk of community-acquired pneumonia of SGLT-2 inhibitors in a real-world setting.
This study will examine the risk of community-acquired pneumonia with SGLT-2 inhibitors using the CPRD linked to hospitalization data. The primary endpoint will be a diagnosis of community-acquired pneumonia. We will use time-dependent Cox proportional hazards models to compare event rates with current use of SGLT-2 inhibitors to those with current use of dipeptidyl peptidase-4 (DPP-4) inhibitors. Secondary analyses will examine if SGLT-2 inhibitors are associated with the risk of hospitalization for community-acquired pneumonia and if the risks differ by SGLT-2 inhibitor molecule, by duration of current use, by dose, by history of respiratory conditions, and by age.
Diagnosis for community acquired pneumonia
- Hospitalization for community acquired pneumonia
- Lower respiratory tract infections
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Corresponding Applicant - McGill University
Laurent Azoulay - Collaborator - McGill University
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Pierre Ernst - Collaborator - McGill University
Robert Platt - Collaborator - McGill University
Vanessa Brunetti - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation