Real-World Evidence of Treatment with Teneligliptin/Canagliflozin Combination Tablets for Type 2 Diabetes Mellitus: A Post-Marketing Surveillance in Japan

Introduction Teneligliptin/canagliflozin combination tablets, which combine a dipeptidyl peptidase-4 (DPP-4) inhibitor (teneligliptin) and a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin), are a treatment option for type 2 diabetes mellitus (T2DM) in Japan. This post-marketing surveillance evaluated the real-world safety and effectiveness of teneligliptin/canagliflozin combination tablets, and changes in self-reported adherence to oral antihyperglycaemic agents. Methods Japanese patients with T2DM who were prescribed the combination tablets for the first time between December 2017 and June 2018 were registered and followed up for 12 months. Safety and effectiveness were assessed in terms of adverse drug reactions (ADRs) and the changes in haemoglobin A1c (HbA1c) and body weight from baseline to 12 months with the last observation carried forward, respectively. Adherence was assessed using the Morisky Medication Adherence Scale 8. Results Overall, 821 patients were eligible for the analyses, including 733 who were prescribed the combination tablets for 12 months. ADRs and serious ADRs were reported in 4.38% and 0.85% of patients, respectively. Gastrointestinal disorders (0.97%) were the most common class of ADRs. No new safety concerns were identified beyond those described in the Japanese package insert. The changes in HbA1c and body weight from baseline to 12 months were - 0.43 +/- 0.93% and - 1.29 +/- 5.57 kg, respectively. The reductions in HbA1c at 12 months tended to be greater among patients who switched from either DPP-4 inhibitors (- 0.71 +/- 0.89%) or SGLT2 inhibitors (- 0.51 +/- 1.00%) relative to patients who switched from both (- 0.22 +/- 0.88%). The decrease in body weight was greatest among patients who switched from DPP-4 inhibitors. An improvement in self-reported adherence to oral antihyperglycaemic agents occurred after switching to the combination tablets. Conclusion Teneligliptin/canagliflozin combination tablets were effective and associated with an improvement in adherence without new safety concerns in Japanese patients with T2DM in real-world clinical practice. Plain Language Summary Teneligliptin/canagliflozin combination tablets are used as an option for the treatment of type 2 diabetes mellitus in Japan. We performed this surveillance to obtain data on the frequency of side effects (adverse drug reactions) and effectiveness (in terms of changes in haemoglobin A1c and body weight) in Japanese patients treated with teneligliptin/canagliflozin combination tablets in real-world clinical practice. We also asked patients to evaluate their adherence to oral antihyperglycaemic agents as part of their prescribed therapies. We collected data for up to 12 months. We detected no new safety concerns, other than those already described in the Japanese package insert for the combination tablets. In terms of effectiveness, we observed improvements in both haemoglobin A1c and body weight over 12 months of treatment. Furthermore, self-reported adherence to oral antihyperglycaemic agents improved after treatment with the combination tablets.