In terms of fractures, a prospectively adjudicated analysis across all phase III studies demonstrated a 0.6% difference in the fracture rate between canagliflozin and non-canagliflozin groups. Analysis by fracture location and trauma classification demonstrated an imbalance in upper limb fractures not favoring canagliflozin. This imbalance persisted in low trauma upper limb fractures and spine (Figure 1). In a pooled analysis of all treatment arms, females had a higher incidence of upper limb fractures (1.2% [31/2608]) compared to placebo (0.4% [5/1338]). The location of distal extremities, including the hand, distal forearm and wrist are similar to the wide variety of fracture sites found in other diseases such a primary hyperparathyroidism.