Sodium/glucose co-transporter 2 inhibitors (SGLT2i) represent a novel class of glucose-lowering agents that lower plasma glucose levels through pharmacological inhibition of glucose reuptake from the kidney, independent of insulin secretion and action. Clinical trials of SGLT2i demonstrated therapeutic benefits on glycemic control and bodyweight in individuals with type 2 diabetes, with few cases of serious adverse events (SAEs). However, a considerable number of SAEs were reported in patients receiving SGLT2i clinically in Japan during the first 3 months of their use. These included urogenital infections, hypoglycemia and dehydration. Unexpectedly, serious skin and subcutaneous disorders, mainly reported as generalized rash or skin eruption, were prominent in patients receiving SGLT2i, but with unknown mechanisms. There is also concern for potential SAEs associated with chronic SGLT2i administration, especially in the non-obese type 2 diabetes characterized by reduced insulin secretion often seen in East Asia. Chronic SAEs may include severe hypoglycemia due to depletion of hepatic glycogen storage, acceleration of diabetes-associated sarcopenia and ketosis/ketoacidosis. The current information on acute SAEs confirms the importance of caution in the appropriate use of SGLT2i. Furthermore, careful long-term observation of patients receiving SGLT2i is essential to avoid SAEs and for better clinical use of this drug class.

This study was initiated to evaluate the association of acute pancreatitis (AP) with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with diabetes in Japan. A retrospective cohort study of a large medical and pharmacy claims database was performed to compare the incidence of AP among those receiving DPP-4 inhibitors and those receiving other oral antidiabetic drugs. The incidence of all AP and hospitalizations for AP was similar between the two groups. Previous exposure to DPP-4 inhibitors did not affect occurrence of AP in patients on other oral antidiabetic drugs. The Kaplan–Meier curve for time to AP was similar between the two groups, and was not affected by previous exposure to DPP-4 inhibitors. The Cox proportional hazard models showed the incidence of AP was not significantly higher in those receiving DPP-4 inhibitors. Despite numerous, important limitations related to claims database-based analyses, our results indicate that there is no increased risk of AP with use of DPP-4 inhibitors among patients with diabetes in Japan.

Aims/IntroductionDipeptidyl peptidase‐4 inhibitors (DPP‐4i) are a common first‐line treatment for type 2 diabetes in Japan. However, little is known about patients’ medication adherence, persistence and discontinuation in this setting.Materials and MethodsThis was a retrospective cohort study of new DPP‐4i users in a Japanese claims database. Adult patients (age 18–65 years) with type 2 diabetes diagnosis and no diagnosis of other diabetes or pregnancy during the study period were included if they were prescribed a DPP‐4i as monotherapy or combination oral therapy. Adherence to therapy was measured using the proportion of days covered method over a fixed period of 1 year. The proportion of days covered of ≥80% was considered adherent. Persistence was defined as continuing index DPP‐4i treatment with <90‐day gap between refills. Patient baseline characteristics were explored as potential predictors of DPP‐4i discontinuation and adherence in multivariable models.ResultsThe final sample contained 2,874 monotherapy and 3,016 dual therapy patients. The mean age was approximately 51 years, and 75% were men. The mean proportion of days covered was 76.6% among monotherapy patients and 82.5% among dual therapy patients, with 67.2% of monotherapy and 74.4% of dual therapy patients classified as adherent. At 12 months, 72.2% of monotherapy and 79.2% of dual therapy patients were persistent. In adjusted models, younger age and having fewer concomitant medications were significantly associated with lower adherence and higher discontinuation, in both treatment groups.ConclusionsThose under the age of 45 years, and those with fewer concomitant medications were less likely to be adherent and persistent, and more likely to discontinue DPP‐4i therapy.

A903fied by age (65-74, 75-84, 85+). Results: In the first year after cohort enrollment, the average monthly anticholinergic burden measured by the ARS, ACB and DBI-Ach was 0.26, 0.60 and 0.04, respectively. Compared to the ARS and DBI-Ach, the ACB showed a strong dose-response relationship with risk for each of the adverse outcomes, particularly in people aged 65-84. For example, in people aged 65-74, ACB scores = 1-4+, emergency room visits: adjusted odds ratio (aOR) ranged from 1.41-2.25, all-cause hospitalization: aOR ranged from 1.32-1.92, fracture-specific hospitalization: aOR ranged from 1.10-1.71, incident dementia: aOR ranged from 3.13-10.01). ConClusions: The ACB scale is more selective than the ARS and the DBI-Ach in identifying medications likely to cause adverse outcomes, including emergency room visits, all-cause hospitalization, fracture-specific hospitalization and incident dementia in the elderly.

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