Increased risk of mycotic infections associated with sodium-glucose co-transporter 2 inhibitors: a prescription sequence symmetry analysis.

AIMS: To determine the risk of mycotic infections associated with the use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in a real-world setting. METHODS: We conducted a prescription sequence symmetry analysis using data from Truven Health MarketScan (2009-2015). We selected continuously enrolled patients newly initiating both an SGLT2i and an antifungal between 1 April 2013 and 31 December 2015 within time periods of 30, 60, 90, 180 or 365 days of each other. Adjusted sequence ratios (ASR) were calculated for each time period as the ratio of patients initiating SGLT2i first over those initiating an antifungal first adjusted for time trends in prescribing. Analyses were stratified by sex and type of SGLT2i. RESULTS: There were 23 276 patients who newly initiated both SGLT2i and an antifungal in our study period. These patients were further classified into those initiating the two drugs within 365 (n = 17 504), 180 (n = 11 873), 90 (n = 7697), 60 (n = 5856) or 30 (n = 3650) days of each other. Increased risks of mycotic infections were present across all time periods, with the strongest effect observed in the 90-day interval [ASR 1.53 (confidence interval, CI 1.43-1.60)]. Findings differed by sex [90-day ASR females: 1.65 (CI 1.56-1.74); males 1.25 (CI 1.14-1.36)] and by SGLT2i [90-day ASR canagliflozin 1.57 (CI 1.49-1.66); non-canagliflozin 1.42 (CI 1.31-1.55)]. CONCLUSION: Initiation of SGLT2i was associated with an increased risk for mycotic infections. Findings from this commercially insured population in the real world are consistent with evidence available from clinical trials.

Sodium-glucose co-transporter 2 inhibitors and the risk of fractures: A propensity score-matched cohort study.

PURPOSE: To determine the risk of fractures associated with sodium-glucose co-transporter 2 inhibitors (SGLT2i) compared with dipeptidyl peptidase-4 inhibitors (DPP4i). METHODS: We conducted a retrospective cohort study using data from the Truven Health MarketScan (2009-2015) databases. Our cohort included patients newly initiating treatment with SGLT2i or DPP-4i between 1 April 2013 and 31 March 2015 that were matched 1:1 using high dimensional propensity scores. Patients were followed up in an as-treated approach starting from initiation of treatment until the earliest of any fracture, treatment discontinuation, disenrollment, or end of data (31 December 2015). Risk of fractures was determined at any time during the follow-up, early in therapy (1-14 days of the follow-up), and later in therapy (15 days and beyond). Cox proportional hazards models were used to determine hazard ratios and robust 95% confidence intervals (95% CI). RESULTS: After matching, our cohort included 30 549 patients in each treatment group. Over a median follow-up of 219 days, there were 745 fractures overall. The most common site for fractures was the foot (32.7%). The effect estimates for fracture risk occurring at any time during follow-up, early in therapy, and later in therapy were HR 1.11 [95% CI 0.96-1.28], HR 1.82 [95% CI 0.99-3.32], and HR 1.07 [95% CI 0.92-1.24], respectively. CONCLUSION: There is a possible increase in risk for fractures early in therapy with SGLT2i. Beyond this initial period, SGLT2is had no apparent effect on the incidence of fractures.

Risk of amputations associated with SGLT2 inhibitors compared to DPP-4 inhibitors: A propensity-matched cohort study.

AIM: To determine the risk of amputations associated with sodium-glucose co-transporter-2 inhibitors (SGLT2i) relative to dipeptidyl peptidase-4 inhibitors (DPP4i). MATERIALS AND METHODS: We conducted an active comparator, new user cohort study using data from the Truven Health MarketScan (2009-2015) databases. Patients aged ≥18 years newly initiating SGLT2i or DPP4i between April 1, 2013 and March 31, 2015 were included. Patients were matched 1:1 on high dimensional propensity scores and followed until the earliest of any amputation, treatment discontinuation, disenrollment or end of study period (December 31, 2015). Cox proportional hazards models were used to estimate hazard ratios (HR) and robust 95% confidence intervals (CI) for amputation risk. RESULTS: There were 30 216 comparable patients in each arm after matching. Over a median follow-up of 0.6 years, there were 60 amputations (SGLT2i: 36; DPP4i: 24), most at the level of partial foot (75%) and associated with diabetes-related vascular disease (66.7%). The incidence of amputations was higher among SGLT2i patients (1.62 vs. 1.15 per 1000 person-years) with a HR of 1.38 (CI: 0.83-2.31). In subgroup analyses, risk differed by type of SGLT2i: canagliflozin, HR 1.15 (CI: 0.63-2.09); dapagliflozin or empagliflozin, HR 2.25 (CI: 0.78-6.47). CONCLUSION: All SGLT2i had an elevated, though not statistically significant, risk for amputations.

Mobile Health Intervention in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Clinical pharmacists and health coaches using mobile health (mHealth) tools, such as telehealth and text messaging, may improve blood glucose levels in African American and Latinx populations with type 2 diabetes. Objective: To determine whether clinical pharmacists and health coaches using mHealth tools can improve hemoglobin A1c (HbA1c) levels. Design, Setting, and Participants: This randomized clinical trial included 221 African American or Latinx patients with type 2 diabetes and elevated HbA1c (≥8%) from an academic medical center in Chicago. Adult patients aged 21 to 75 years were enrolled and randomized from March 23, 2017, through January 8, 2020. Patients randomized to the intervention group received mHealth diabetes support for 1 year followed by monitored usual diabetes care during a second year (follow-up duration, 24 months). Those randomized to the waiting list control group received usual diabetes care for 1 year followed by the mHealth diabetes intervention during a second year. Interventions: The mHealth diabetes intervention included remote support (eg, review of glucose levels and medication intensification) from clinical pharmacists via a video telehealth platform. Health coach activities (eg, addressing barriers to medication use and assisting pharmacists in medication reconciliation and telehealth) occurred in person at participant homes and via phone calls and text messaging. Usual diabetes care comprised routine health care from patients' primary care physicians, including medication reconciliation and adjustment. Main Outcomes and Measures: Outcomes included HbA1c (primary outcome), blood pressure, cholesterol, body mass index, health-related quality of life, diabetes distress, diabetes self-efficacy, depressive symptoms, social support, medication-taking behavior, and diabetes self-care measured every 6 months. Results: Among the 221 participants (mean [SD] age, 55.2 [9.5] years; 154 women [69.7%], 148 African American adults [67.0%], and 73 Latinx adults [33.0%]), the baseline mean (SD) HbA1c level was 9.23% (1.53%). Over the initial 12 months, HbA1c improved by a mean of -0.79 percentage points in the intervention group compared with -0.24 percentage points in the waiting list control group (treatment effect, -0.62; 95% CI, -1.04 to -0.19; P = .005). Over the subsequent 12 months, a significant change in HbA1c was observed in the waiting list control group after they received the same intervention (mean change, -0.57 percentage points; P = .002), while the intervention group maintained benefit (mean change, 0.17 percentage points; P = .35). No between-group differences were found in adjusted models for secondary outcomes. Conclusions and Relevance: In this randomized clinical trial, HbA1c levels improved among African American and Latinx adults with type 2 diabetes. These findings suggest that a clinical pharmacist and health coach-delivered mobile health intervention can improve blood glucose levels in African American and Latinx populations and may help reduce racial and ethnic disparities. Trial Registration: ClinicalTrials.gov Identifier: NCT02990299.