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Introduction: Disaster Medicine (DM) is defined by Koenig and Shultz as the “disciplines and organizations involved with governmental public health, public and private medical delivery including Emergency Medical Services (EMS), and governmental emergency management.” The Accreditation Council for Graduate Medical Education (ACGME) sets curriculum requirements and standards for Emergency Medicine (EM) residencies and EMS fellowships, which include a limited portion of the DM curriculum topics recommended by the Society of Academic Emergency Medicine (SAEM). The ACGME does not currently approve DM fellowships, as DM is not recognized as a subspecialty by the American Board of Medical Specialties (ABMS). This lack of nationally standardized guidelines for DM training leads to variability in disaster-related knowledge and skills, even among physicians trained by ACGME-accredited programs. Study Objective: The objective of this study is to analyze the DM components covered in EM residency and EMS fellowship in the United States and compare those to SAEM DM fellowship curriculum guidelines. Methods: The DM curriculum components of EM residencies and EMS fellowships were evaluated, using the SAEM DM curriculum as a control. Overlapping topics, as well as gaps between the programs, were analyzed using descriptive statistics. Results: Of the DM curriculum components developed by SAEM, EMS fellowship covered 15 of 19 (79%) major curriculum components and 38 of 99 (38%) subtopics, while EM residency covered seven of 19 major curriculum components (37%) and 16 of 99 (16%) subtopics. Together, EM residency and EMS fellowship cover 16 of 19 (84%) major curriculum components and 40 of 99 (40%) subtopics. Conclusion: While EMS fellowship covers a large portion of the DM major curriculum components recommended by SAEM, there are several important DM subtopics that are not covered either in EM residency or EMS fellowship. Furthermore, there is no standardization for the depth and manner that DM topics are addressed in either curriculum. Time constraints in EM residency and EMS fellowship may also prevent extensive review of important DM topics. Disaster Medicine covers a distinct body of knowledge, represented in the curriculum subtopics, that are not covered in either EM residency or EMS fellowship. The development of an ACGME-accredited DM fellowship and recognition of DM as a distinct subspecialty could allow for more effective DM graduate medical education.

The effect of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the total (first and recurrent) burden of cardiovascular (CV) hospitalizations, including hospitalization for heart failure, myocardial infarction, and stroke, is poorly understood.To assess the effect of empagliflozin, an SGLT2i, on total CV hospitalizations among older adults with T2D.Using data from Medicare fee-for-service (08/2014-09/2017), we identified 1:1 propensity score-matched cohorts of patients with T2D initiating empagliflozin versus sitagliptin or empagliflozin versus glucagon-like peptide-1 receptor agonists (GLP-1RA), balancing140 baseline covariates. We compared the risk of first and recurrent hospitalizations with any CV condition as the primary discharge diagnosis (ICD-9: 390-459; ICD-10: I00-I99), hospitalizations for heart failure (HHF), and myocardial infarctions (MI) or stroke. We estimated treatment effects based on the Ghosh-Lin semiparametric model for recurrent events as primary and joint frailty model as secondary analysis.We included 11,429 matched-pairs of empagliflozin and sitagliptin initiators and 17,502 matched-pairs of empagliflozin and GLP1-RA initiators with an average age of 72 years. Empagliflozin was associated with a reduced risk of total CV hospitalizations (0.80 [0.69-0.93] vs sitagliptin; 0.88 [0.77-1.00] vs GLP-1RA) and total HHF (0.70 [0.51-0.98] vs sitagliptin; 0.76 [0.56-1.03] vs GLP1-RA) over a mean follow up of 6.3 months. No differences between treatments were observed for MI or stroke. Results were consistent for joint frailty models.Empagliflozin, compared to sitagliptin or to a lesser extent GLP1-RA, was associated with a reduction in the burden of total CV hospitalizations and HHF in older patients with T2D.

The Reach Ahead for Lifestyle and Health (REAL HEALTH)-Diabetes study assessed the comparative effectiveness of two Look AHEAD (Action for Health in Diabetes)-adapted lifestyle intervention (LI) arms targeting weight loss in type 2 diabetes compared with medical nutrition therapy (MNT) referral. At 1 year, LI had greater weight loss than MNT. This study reports outcomes at 24 (end of LI) and 36 months.Participants (N = 211) with type 2 diabetes and BMI 25 kg/mParticipants were 61.7 (SD 10.2) years old; 55% were female; 77% were non-Hispanic White; and had mean (SD) weight of 98 (18.9) kg and mean (SD) HbA1c of 7.7% (1.2%). Mean (SD) weight change at 24 and 36 months was -4.4% (5.9%) and -4.4% (5.4%) in in-person LI, -4.0% (5.8%) and -5.3% (6.4%) in telephone LI, and -3.1% (5.2%) and -5.8% (7.1%) in MNT, with no statistically significant difference in weight or HbA1c at 24 and 36 months. Compared with MNT, LI arms had favorable changes in patient-reported outcomes related to learned dietary skills.There were no differences in weight outcomes among LI participants compared with referral to MNT at the end of intervention or 1 year after its conclusion.

Background Severe hypoglycemia is associated with adverse clinical outcomes. We evaluated the risk of severe hypoglycemia in older adults initiating newer glucose-lowering medications overall and across strata of known indicators of high hypoglycemia risk. Methods We conducted a comparative-effectiveness cohort study of older adults aged >65 years with type 2 diabetes initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) or SGLT2i versus glucagon-like peptide-1 receptor agonists (GLP-1RA) using Medicare claims (3/2013–12/2018) and Medicare-linked-electronic health records. We identified severe hypoglycemia requiring emergency or inpatient visits using validated algorithms. After 1:1 propensity score matching, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years. Analyses were stratified by baseline insulin, sulfonylurea, cardiovascular disease (CVD), chronic kidney disease (CKD), and frailty. Results Over a median follow-up of 7 (interquartile range: 4–16) months, SGLT2i was associated with a reduced risk of hypoglycemia versus DPP-4i (HR 0.75 [0.68, 0.83]; RD −3.21 [−4.29, −2.12]), and versus GLP-1RA (HR 0.90 [0.82, 0.98]; RD −1.33 [−2.44, −0.23]). RD for SGLT2i versus DPP-4i was larger in patients using baseline insulin than in those not, although HRs were similar. In patients using baseline sulfonylurea, the risk of hypoglycemia was lower in SGLT2i versus DPP-4i (HR 0.57 [0.49, 0.65], RD −6.80 [−8.43, −5.16]), while the association was near-null in those without baseline sulfonylurea. Results stratified by baseline CVD, CKD and frailty were similar to the overall cohort findings. Findings for the GLP-1RA comparison were similar. Conclusions SGLT2i was associated with a lower hypoglycemia risk versus incretin-based medications, with larger associations in patients using baseline insulin or sulfonylurea.

OBJECTIVE We aimed to understand the factors associated with sodium–glucose cotransporter 2 inhibitor (SGLT2i) adherence and longitudinal adherence trajectories in older adults with type 2 diabetes. RESEARCH DESIGN AND METHODS Using Medicare claims data (April 2013–December 2017), we identified 83,675 new SGLT2i users ≥66 years old with type 2 diabetes. We measured SGLT2i adherence as the proportion of days covered (PDC) during the first year of SGLT2i therapy. We used linear regression to assess the association between baseline covariates and PDC. Then we used group-based trajectory modeling to identify distinct longitudinal SGLT2i adherence groups and used a multivariable logistic regression model to examine the association between baseline covariates and membership in these adherence groups. RESULTS Unadjusted mean PDC was 63%. Previous adherence to statins had the strongest positive association with PDC (regression coefficient 6.00% [95% CI 5.50, 6.50]), whereas female sex (−5.51% [−6.02, −5.00]), and Black race/ethnicity (−5.06% [−6.03, −4.09]) had the strongest negative association. We identified three adherence trajectory groups: low (23% of patients, mean PDC 17%), moderate (32%, mean PDC 50%), and high (45%, mean PDC 96%) adherence. More patients in the high adherence group were previously adherent to statins (odds ratio 1.43 [95% CI 1.39, 1.48]), and more women (1.28 [1.23, 1.32]) and Black patients (1.31 [1.23, 1.40]) were in the low adherence group. CONCLUSIONS In a large population of older patients with type 2 diabetes, 45% were highly adherent during the first year of SGLT2i treatment. Female sex and Black race/ethnicity were most strongly associated with low adherence.

Objective: To compare the Emergency Severity Index (ESI) and Sort Assess Life Saving Interventions Treatment and Transport (SALT) triage categories for an existing emergency department (ED) patient population.Design: A prospective, cross-sectional study.Setting: An academic-affiliated community teaching ED at a Level 1 Trauma Center.Participants: All patients presenting to the ED over 2 nonconsecutive 24-hour weekdays.Main outcome measures: The correlation between triage system classifications was assessed using the Spearman’s rank correlation coefficient.Results: 100 percent of ESI 5, 83.3 percent of ESI 4, and 70.4 percent of ESI 3 were categorized as Minimal under SALT. 70.8 percent of ESI 2 was categorized as Delayed, and 71.4 percent of ESI 1 designations correlated with Immediate. Spearman’s rank correlation coefficient was 0.509 (p 0.001).Conclusion: This study results suggest that ESI moderately correlates with SALT, particularly in lower acuity patients. This result may inform future protocol development for rapid triage of existing ED populations prior to the arrival of patients from a mass casualty event.

ImportanceLimited evidence is available on the comparative effectiveness of empagliflozin vs alternative second-line glucose-lowering agents in patients with type 2 diabetes (T2D) receiving routine care who have a broad spectrum of cardiorenal risk.ObjectiveTo evaluate the association of empagliflozin with cardiovascular outcomes relative to liraglutide and sitagliptin, stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD).Design, Setting, and ParticipantsThis retrospective comparative effectiveness cohort study used deidentified Medicare claims data from August 1, 2014, to September 30, 2018, with follow-up from drug initiation until treatment changes, death, or gap in Medicare enrollment (>30 days). Data analysis was performed from October 1, 2021, to April 30, 2022. Medicare fee-for-service beneficiaries older than 65 years with T2D were included. A total of 45 788 patients (22 894 propensity score–matched pairs initiating treatment with either empagliflozin or liraglutide) were included in cohort 1, and 45 624 patients (22 812 propensity score–matched pairs initiating treatment with either empagliflozin or sitagliptin) were included in cohort 2.ExposuresEmpagliflozin vs liraglutide (cohort 1) or empagliflozin vs sitagliptin (cohort 2).Main Outcomes and MeasuresPrimary outcomes were (1) modified major adverse cardiovascular events (MACEs), including a composite of myocardial infarction, stroke, and all-cause mortality, and (2) hospitalization for heart failure (HHF). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, adjusting for 143 baseline covariates using 1:1 propensity score matching.ResultsAmong 45 788 patients in cohort 1, the mean (SD) age was 71.9 (5.1) years; 23 396 patients (51.1%) were female, 22 392 (48.9%) were male, and 38 049 (83.1%) were White. Among 45 624 patients in cohort 2, the mean (SD) age was 72.1 (5.1) years; 21 418 patients (46.9%) were female, 24 206 (53.1%) were male, and 37 814 (82.9%) were White. Relative to patients initiating liraglutide, those initiating empagliflozin had a similar risk of the modified MACE outcome (HR, 0.90; 95% CI, 0.79-1.03) and a reduced risk of HHF (HR, 0.66; 95% CI, 0.52-0.82). Across subgroups, empagliflozin was associated with a lower risk of the modified MACE outcome in patients with a history of ASCVD (HR, 0.83; 95% CI, 0.71-0.98) and HF (HR, 0.77; 95% CI, 0.60-1.00) compared with liraglutide, and potential heterogeneity in estimates was observed by sex (male: HR, 0.85 [95% CI, 0.71-1.01]; female: HR, 1.16 [95% CI, 0.94-1.42]; P = .02 for homogeneity). However, reductions in the risk of HHF were observed across most subgroups (eg, ASCVD: HR, 0.66 [95% CI, 0.51-0.85]; HF: HR, 0.66 [95% CI, 0.49-0.88]). Compared with sitagliptin, empagliflozin was associated with reduced risks of the modified MACE outcome (HR, 0.68; 95% CI, 0.60-0.77) and HHF (HR, 0.45; 95% CI, 0.36-0.56), which were consistent across all subgroups. Absolute benefits of empagliflozin vs sitagliptin were larger in patients with a history of ASCVD (modified MACE: RD, −17.6 [95% CI, −24.9 to −10.4]; HHF: RD, −16.7 [95% CI, −21.7 to −11.9]), HF (modified MACE: RD, −41.1 [95% CI, −59.9 to −22.6]; HHF: RD, −50.4 [95% CI, −67.5 to −33.9]), or CKD (modified MACE: RD, −26.7 [95% CI, −41.3 to −12.3]; HHF: RD, −31.9 [95% CI, −43.5 to −20.8]).Conclusions and RelevanceIn this comparative effectiveness study of older adults, empagliflozin was associated with a lower risk of HHF (relative to both liraglutide and sitagliptin) and the modified MACE outcome (relative to sitagliptin), with larger absolute benefits in patients with established cardiorenal diseases. These findings suggest that older adults with T2D might benefit more from empagliflozin vs liraglutide or sitagliptin with respect to the risk of HHF; with respect to the risk of MACEs, empagliflozin might be preferable to liraglutide only in patients with cardiovascular disease history and to sitagliptin across all patient subgroups.

ImportanceSodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated many cardiovascular and kidney function benefits for patients with type 2 diabetes (T2D). However, the results of SGLT-2i use in primary prevention of atrial fibrillation (AF) were inconsistent in clinical trials, and incident AF was not a prespecified end point.ObjectiveTo examine incident AF with initiation of an SGLT-2i compared with initiation of a dipeptidyl peptidase-4 inhibitor (DPP-4i) or a glucagonlike peptide-1 receptor agonist (GLP-1RA) among older adults (aged ≥66 years) with T2D in routine clinical practice.Design, Setting, and ParticipantsA population-based new-user cohort study included older adults with T2D who had no history of AF and were enrolled in Medicare fee-for-service from April 1, 2013, to December 31, 2018. Data analysis was performed from June 28 to December 1, 2021.ExposuresTo control for potential confounding, new users of SGLT-2i were 1:1 propensity score (PS)–matched to new users of DPP-4is or GLP-1RAs in 2 pairwise comparisons based on 138 baseline covariates.Main Outcomes and MeasuresThe primary outcome was incident AF, defined as an inpatient diagnosis code for AF. Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years, with their 95% CIs, were estimated in the PS-matched groups.ResultsNew users of SGLT-2is were 1:1 PS-matched to new users of a DPP-4i (n = 74 868) or GLP-1RA (n = 80 475). Overall, the mean (SD) age of study participants was 72 (5) years, and 165 984 were women (53.4%). The risk of incident AF was lower in the SGLT-2i group than the matched DPP-4i group (HR, 0.82; 95% CI, 0.76 to 0.89; RD, –3.7; 95% CI, –5.2 to –2.2 per 1000 person-years) or the matched GLP-1RA group (HR, 0.90; 95% CI, 0.83 to 0.98; RD, –1.8; 95% CI, –3.2 to –0.3 per 1000 person-years). Results were consistent across several sensitivity and subgroup analyses.Conclusions and RelevanceThe findings of this study suggest that the initiation of an SGLT-2i was associated with a reduced risk of incident AF compared with a DPP-4i or GLP-1RA. The results may be helpful when weighing the potential risks and benefits of various glucose level–lowering agents in older adults with T2D.

The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain.In this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the effectiveness of four commonly used glucose-lowering medications. We randomly assigned participants to receive insulin glargine U-100 (hereafter, glargine), the sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or sitagliptin, a dipeptidyl peptidase 4 inhibitor. The primary metabolic outcome was a glycated hemoglobin level, measured quarterly, of 7.0% or higher that was subsequently confirmed, and the secondary metabolic outcome was a confirmed glycated hemoglobin level greater than 7.5%.A total of 5047 participants (19.8% Black and 18.6% Hispanic or Latinx) who had received metformin for type 2 diabetes were followed for a mean of 5.0 years. The cumulative incidence of a glycated hemoglobin level of 7.0% or higher (the primary metabolic outcome) differed significantly among the four groups (P0.001 for a global test of differences across groups); the rates with glargine (26.5 per 100 participant-years) and liraglutide (26.1) were similar and lower than those with glimepiride (30.4) and sitagliptin (38.1). The differences among the groups with respect to a glycated hemoglobin level greater than 7.5% (the secondary outcome) paralleled those of the primary outcome. There were no material differences with respect to the primary outcome across prespecified subgroups defined according to sex, age, or race or ethnic group; however, among participants with higher baseline glycated hemoglobin levels there appeared to be an even greater benefit with glargine, liraglutide, and glimepiride than with sitagliptin. Severe hypoglycemia was rare but significantly more frequent with glimepiride (in 2.2% of the participants) than with glargine (1.3%), liraglutide (1.0%), or sitagliptin (0.7%). Participants who received liraglutide reported more frequent gastrointestinal side effects and lost more weight than those in the other treatment groups.All four medications, when added to metformin, decreased glycated hemoglobin levels. However, glargine and liraglutide were significantly, albeit modestly, more effective in achieving and maintaining target glycated hemoglobin levels. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).

Summary Background The prevalence of overweight, obesity, and diabetes is rising rapidly in low-income and middle-income countries (LMICs), but there are scant empirical data on the association between body-mass index (BMI) and diabetes in these settings. Methods In this cross-sectional study, we pooled individual-level data from nationally representative surveys across 57 LMICs. We identified all countries in which a WHO Stepwise Approach to Surveillance (STEPS) survey had been done during a year in which the country fell into an eligible World Bank income group category. For LMICs that did not have a STEPS survey, did not have valid contact information, or declined our request for data, we did a systematic search for survey datasets. Eligible surveys were done during or after 2008; had individual-level data; were done in a low-income, lower-middle-income, or upper-middle-income country; were nationally representative; had a response rate of 50% or higher; contained a diabetes biomarker (either a blood glucose measurement or glycated haemoglobin [HbA1c]); and contained data on height and weight. Diabetes was defined biologically as a fasting plasma glucose concentration of 7·0 mmol/L (126·0 mg/dL) or higher; a random plasma glucose concentration of 11·1 mmol/L (200·0 mg/dL) or higher; or a HbA1c of 6·5% (48·0 mmol/mol) or higher, or by self-reported use of diabetes medication. We included individuals aged 25 years or older with complete data on diabetes status, BMI (defined as normal [18·5–22·9 kg/m2], upper-normal [23·0–24·9 kg/m2], overweight [25·0–29·9 kg/m2], or obese [≥30·0 kg/m2]), sex, and age. Countries were categorised into six geographical regions: Latin America and the Caribbean, Europe and central Asia, east, south, and southeast Asia, sub-Saharan Africa, Middle East and north Africa, and Oceania. We estimated the association between BMI and diabetes risk by multivariable Poisson regression and receiver operating curve analyses, stratified by sex and geographical region. Findings Our pooled dataset from 58 nationally representative surveys in 57 LMICs included 685 616 individuals. The overall prevalence of overweight was 27·2% (95% CI 26·6–27·8), of obesity was 21·0% (19·6–22·5), and of diabetes was 9·3% (8·4–10·2). In the pooled analysis, a higher risk of diabetes was observed at a BMI of 23 kg/m2 or higher, with a 43% greater risk of diabetes for men and a 41% greater risk for women compared with a BMI of 18·5–22·9 kg/m2. Diabetes risk also increased steeply in individuals aged 35–44 years and in men aged 25–34 years in sub-Saharan Africa. In the stratified analyses, there was considerable regional variability in this association. Optimal BMI thresholds for diabetes screening ranged from 23·8 kg/m2 among men in east, south, and southeast Asia to 28·3 kg/m2 among women in the Middle East and north Africa and in Latin America and the Caribbean. Interpretation The association between BMI and diabetes risk in LMICs is subject to substantial regional variability. Diabetes risk is greater at lower BMI thresholds and at younger ages than reflected in currently used BMI cutoffs for assessing diabetes risk. These findings offer an important insight to inform context-specific diabetes screening guidelines. Funding Harvard T H Chan School of Public Health McLennan Fund: Dean's Challenge Grant Program.

Summary Background Approximately 80% of the 463 million adults worldwide with diabetes live in low-income and middle-income countries (LMICs). A major obstacle to designing evidence-based policies to improve diabetes outcomes in LMICs is the scarce availability of nationally representative data on the current patterns of treatment coverage. The objectives of this study were to estimate the proportion of adults with diabetes in LMICs who receive coverage of recommended pharmacological and non-pharmacological diabetes treatment; and to describe country-level and individual-level characteristics that are associated with treatment. Methods We did a cross-sectional analysis of pooled, individual data from 55 nationally representative surveys in LMICs. Our primary outcome of self-reported diabetes treatment coverage was based on population-level monitoring indicators recommended in the 2020 WHO Package of Essential Noncommunicable Disease Interventions. Surveys were included if they were done in 2008 or after in an LMIC, as classified by the World Bank in the year the survey was done; were nationally representative; had individual-level data; contained a diabetes biomarker (fasting glucose, random glucose, or glycated haemoglobin); and had data on one or more diabetes treatments. Our sample included non-pregnant individuals with an available diabetes biomarker who were at least 25 years of age. We assessed coverage of three pharmacological and three non-pharmacological treatments among people with diabetes. At the country level, we estimated the proportion of individuals reporting coverage by per-capita gross national income and geographical region. At the individual level, we used logistic regression models to assess coverage along several key individual characteristics including sex, age, body-mass index, wealth quintile, and educational attainment. In the primary analysis, we scaled sample weights such that countries were weighted equally. Findings The final pooled sample from the 55 LMICs included 680 102 total individuals and 37 094 individuals with diabetes. Using equal weights for each country, diabetes prevalence was 9·0% (95% CI 8·7–9·4), with 43·9% (41·9–45·9) reporting a previous diabetes diagnosis. Overall, 4·6% (3·9–5·4) of individuals with diabetes self-reported meeting need for all treatments recommended for them. Coverage of glucose-lowering medication was 50·5% (48·6–52·5); antihypertensive medication was 41·3% (39·3–43·3); cholesterol-lowering medication was 6·3% (5·5–7·2); diet counselling was 32·2% (30·7–33·7); exercise counselling was 28·2% (26·6–29·8); and weight-loss counselling was 31·5% (29·3–33·7). Countries at higher-income levels tended to have greater coverage. Female sex and higher age, body-mass index, educational attainment, and household wealth were also associated with greater coverage. Interpretation Fewer than one in ten people with diabetes in LMICs receive coverage of guideline-based comprehensive diabetes treatment. Scaling up the capacity of health systems to deliver treatment not only to lower glucose but also to address cardiovascular disease risk factors, such as hypertension and high cholesterol, are urgent global diabetes priorities. Funding National Clinician Scholars Program at the University of Michigan Institute for Healthcare Policy & Innovation, National Institute of Diabetes and Digestive and Kidney Diseases, Harvard Catalyst, and National Center for Advancing Translational Sciences of the National Institutes of Health.

Objective: Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to treatment intensification. Research Design and Methods: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study enrolled participants with type 2 diabetes duration ≥65 years) using ANOVA and Pearson’s chi-squared tests.. Results: Within the GRADE cohort (n=5,047), we observed significant differences by age with younger adults having greater racial diversity, fewer medications for common comorbidities, lower prevalence of CVD, higher weight and BMI, more pronounced hyperglycemia and diabetic dyslipidemia, with metabolic profile indicating lower insulin sensitivity (1/fasting insulin, HOMA-2S, Matsuda index) and inadequate β cell response (oral disposition index) (p < 0.05 across age categories). Conclusions: Clinical and metabolic characteristics of type 2 diabetes differ by age within the GRADE cohort. Younger adults exhibit more prominent obesity-related characteristics, including higher obesity levels, lower insulin sensitivity and beta cell compensation. Given the increasing burden of type 2 diabetes and complications, particularly among younger populations, these age-related distinctions may inform risk factor management approaches and treatment priorities. Further study will determine whether age-related differences impact response to therapy.

Measures of depression (e.g., PHQ-8) and diabetes-related distress (e.g., Problem Areas In Diabetes, or PAID) are associated with diabetes self-care and adherence to lifestyle regimens in patients with T2D. The REAL HEALTH-Diabetes trial evaluated a Look-AHEAD adapted group lifestyle intervention (LI) . We sought to determine baseline characteristics that were associated with achieving ≥5% weight loss during the first year of the intervention. Participants were randomly assigned to receive LI either in-person (IP, n = 69) or by telephone (Tele, n =72) . At baseline, 12.9% had a PHQ-8 score of ≥ 10, indicating current depression, and 50.4% had a baseline PAID score of ≥ 40, indicating severe emotional distress. At 6 months and 12 months, 46.8% and 45.7% achieved ≥ 5% weight loss (Table 1) . Participants who achieved ≥ 5% weight loss at 6 and 12 months had lower mean baseline PAID scores than non-achievers (35 vs. 44, P=0.021 at 6 months; 35 vs. 43, P=0.036 at 12 months) . Achievers also had lower mean baseline PHQ-8 scores compared to non-achievers, but this difference was not statistically significant (4.0 vs. 5.1, P=0.596 at 6 months; 3.8 vs. 5.1, P=0.842 at 12 months) . We found that diabetes distress was more common than depression, and that baseline levels of diabetes-related distress were inversely associated with achievement of ≥ 5% weight loss at 6 and 12 months of LI. Disclosure J.Vakharia: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. T.Thaweethai: None. C.Yu: None. L.M.Delahanty: Advisory Panel; Lilly Diabetes, Omada Health, Inc., WW International, Inc., ZOE Limited, Stock/Shareholder; Jana Care Inc., Omada Health, Inc., ZOE Limited. Funding T32 DK007028

Background: SGLT2i and GLP1-RA improve cardiovascular (CV) and renal outcomes in patients with T2D who are at elevated cardiac or renal risk; however, prescription rates are low despite guidelines recommending their use. We aimed to evaluate the eligibility for and utilization of SGLT2i and GLP-1 in a large health system (HS) . Methods: The electronic health record (EHR) at a quaternary HS in the Northeastern US was queried to identify patients with T2D with CV, renal disease, or at high CV risk based on comorbidities and 10-year atherosclerotic CV disease (ASCVD) risk score. Demographics, medications, comorbidities, indications, and contraindications for SGLT2i and/or GLP1-RA therapy were assessed. Results: The population of individuals with T2D on metformin therapy consists of 122,537 patients: 55% male, 8% Black, 13% non-English speaking. Of patients eligible for SGLT2i, 12% were prescribed an SGLT2i. Of patients eligible for GLP1-RA therapy, 17% were prescribed GLP1-RA. Of patients eligible for either SGLT2i or GLP1-RA therapy not currently receiving either therapy, 41% had 10-year ASCVD risk >10%, 56% had ASCVD, 29% had chronic kidney disease (CKD) , and 18% had heart failure. Conclusion: While advantages of novel therapies have demonstrated benefits, opportunities from provider, patient, and systems to eliminate barriers to uptake and dissemination of therapy to improve outcomes for patients exist. Disclosure A.Blood: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. B.M.Scirica: Consultant; Allergan, Boehringer Ingelheim International GmbH, ESPERION Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Novo Nordisk, Research Support; Better Therapeutics, Eisai Co., Ltd., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Stock/Shareholder; Heath At Scale. F.Waterman: Employee; Novo Nordisk. G.Stern: None. D.Zelle: None. L.Chang: Consultant; Alosa Health, Pri-Med LLC, Other Relationship; Applied Therapeutics, Better Therapeutics, Eli Lilly and Company, Fractyl Health, Inc., Sanofi, Research Support; Boehringer Ingelheim International GmbH, Novo Nordisk. C.A.Colling: None. D.Gabovitch: None. C.M.Hamersky: Employee; Novo Nordisk. E.Durden: Employee; Novo Nordisk A/S. C.Holt: Employee; Novo Nordisk. J.Noone: Employee; Novo Nordisk. C.P.Cannon: Advisory Panel; Alnylam Pharmaceuticals, Inc., Amarin Corporation, Amgen Inc., Amryt Pharma Plc, Applied Therapeutics, Ascendis Pharma A/S, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Rhoshan, Sanofi, Research Support; Amgen Inc., Better Therapeutics, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc. Funding Novo Nordisk

The role of SGLT-2i in the primary prevention of atrial fibrillation (AF) remains unclear from clinical trials. We assessed the association of SGLT-2i use and incident AF in routine clinical practice. Using Medicare claims data 2013-2018, we identified patients with type 2 diabetes (T2D) and aged ≥66 years with no AF history (i.e., no diagnosis, procedure or medication codes suggestive of underlying AF at baseline) initiating an SGLT-2i or a comparator (a DPP-4i or a GLP-1RA) , in two pairwise comparisons (74,868 and 80,475 1:1 propensity score-matched pairs, respectively) . The primary outcome was AF hospitalization. Secondary outcomes were AF diagnosis in any care setting and AF treated with medications. We calculated hazard ratios (HRs) and rate differences (RDs, per 1000 patient-year) , in the matched groups, well-balanced across 138 baseline covariates. Over a median follow-up of approximately 6 months, the risk of AF hospitalization was lower in the SGLT-2i group than the DPP-4i group (HR, 0.82 [95%CI, 0.76-0.89]; RD, -3.7 [95%CI, -5.2, -2.2]) or the GLP-1RA group (HR, 0.90 [95%CI, 0.83-0.98]; RD, -1.8 [95%CI, -3.2, -0.3]) (Table) . Findings for secondary outcomes were consistent with the primary outcome. In routine care, SGLT-2i use was associated with a reduction in the risk of incident AF, compared to DPP-4i or GLP-1RA among older patients with T2D. Disclosure M.Zhuo: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. B.M.Everett: Consultant; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Lilly, Provention Bio, Inc., UpToDate, Other Relationship; American Heart Association, Research Support; Novo Nordisk. E.D'andrea: None. R.Glynn: None. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute.

SGLT2 inhibitors (SGLT2i) are increasingly prescribed to treat type 2 diabetes (T2D) given their cardiovascular benefits. However, SGLT2i are known to increase the risk of diabetic ketoacidosis (DKA) , a rare yet serious outcome. It remains unclear whether individual SGLT2i are associated with a differential risk of DKA. Using 3 US healthcare claims databases (1/2014 - 12/2020) we assembled 2 cohorts of adults with T2D initiating (1) individual SGLT2i, i.e., canagliflozin, dapagliflozin, or empagliflozin, for a within-class comparison between SGLT2i (cohort #1, median age=62 years, 55% male) , and (2) individual SGLT2i or dulaglutide, for comparisons between SGLT2i and an out-of-class comparison (cohort #2, median age=63 years, 54% male) . Cohorts were reweighed using inverse probability of treatment weights, accounting for >130 baseline patient characteristics. Hazard ratios (HRs) and 95% CIs were estimated for hospitalization for DKA in each database and pooled using random-effects models. Over a median follow-up of 6 months, neither empagliflozin [HR (95% CI) = 0.96 (0.78-1.19) ], or dapagliflozin [HR (95% CI) = 0.76 (0.58-1.01) ] had a differential DKA risk vs. canagliflozin. All 3 SGLT2i were associated with a similar increase in DKA risk vs. dulaglutide (Table) . In this large cohort study, we found no difference in the risk of DKA across individual SGLT2i, but all SGLT2i types were associated with an increased risk of DKA vs. dulaglutide. Disclosure D.Abrahami: None. E.D'andrea: None. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. J.M.Paik: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. Funding Patient-Centered Outcomes Research Institute (DB-2020C2-20326)

Within the EMPRISE® monitoring program, we evaluated the cardiovascular effectiveness of empagliflozin (EMPA) vs. glucagon-like peptide-1 receptor agonists (GLP1RA) or liraglutide using data from Medicare and 2 U.S. commercial claims databases [2014- (2018 for Medicare) ]. We identified patients ≥18 years with type 2 diabetes initiating (i) EMPA vs. GLP1-RA or (ii) EMPA vs. liraglutide. Primary outcomes were hospitalization for heart failure (HHF) , myocardial infarction (MI) , stroke, and all-cause mortality (Medicare only) . After 1:1 propensity score matching, we estimated pooled HR (95% CI) overall and in subgroups of patients with and without baseline cardiovascular disease (CVD) . We identified 105,955 pairs of EMPA vs. GLP1RA initiators and 72,498 pairs of EMPA vs. liraglutide initiators (Table) . Relative to GLP1RA, EMPA had a lower risk of HHF [HR:0.62 (95% CI, 0.53, 0.71) ] and a similar risk of MI [0.95 (0.85, 1.07) ], stroke [1. (0.94, 1.27) ], and mortality [0.91 (0.77, 1.08) ]. Results were consistent for patients with and without CVD. When we compared EMPA vs. liraglutide, estimates were similar to those from GLP1 RA, both overall and across subgroups. Among real-world patients, EMPA was associated with a reduced risk of HHF, but with similar risk of MI, stroke, and mortality, across the broad spectrum of CVD, compared with GLP-1RA overall or liraglutide. Disclosure P.T.Htoo: Employee; Johnson & Johnson. S.Schneeweiss: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. H.Tesfaye: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. M.Najafzadeh: None. R.Glynn: Research Support; Amarin Corporation, AstraZeneca, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. A.Deruaz-luyet: Employee; Boehringer Ingelheim International GmbH, Other Relationship; IQVIA Inc., Sanofi. S.F.Fazeli farsani: Employee; Boehringer Ingelheim International GmbH. L.Koeneman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

EMPRISE is a 5-year monitoring program that evaluates the effectiveness and safety of empagliflozin (EMPA) using Medicare and 2 U.S. commercial claims [2014-20 (2018 for Medicare) ]. We identified 190,226 patients ≥18 years with type 2 diabetes initiating EMPA or a dipeptidyl peptidase-4 inhibitors (DPP-4i) , and followed them up for heart failure hospitalization in primary (HHF-Specific) or any discharge positions (HHF-Broad) , a composite of myocardial infarction (MI) and stroke, and all-cause mortality (ACM) (Medicare only) . Safety outcomes were lower-limb amputations (LLA) , non-vertebral fractures, diabetic ketoacidosis (DKA) , acute kidney injury (AKI) , renal and bladder cancers (CA) . We estimated pooled HR (95% CI) after propensity score matching, adjusting for 143 baseline covariates. Compared to DPP4i, EMPA was associated with a reduced risk of HHF [HHF-Specific: 0.47 (0.41, 0.55) ; HHF-Broad: 0.67 (0.62, 0.72) ], a similar risk of the composite of MI or stroke [0.92 (0.84, 1.02) ], and a reduced risk of ACM [0.56 (0.46, 0.68) ]. EMPA was associated with a reduced risk of AKI [0.73 (0.68, 0.78) ], an increased risk of DKA [1.88 (1.51, 2.34) ], and a similar risk of LLA, fractures, and renal and bladder CA. Our findings support the cardiovascular effectiveness of EMPA in routine care with a safety profile in line with documented information. Disclosure P.T.Htoo: Employee; Johnson & Johnson. S.Schneeweiss: Consultant; Aetion, Inc., Research Support; Boehringer Ingelheim International GmbH. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. H.Tesfaye: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. M.Najafzadeh: None. R.Glynn: Research Support; Amarin Corporation, AstraZeneca, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. A.Deruaz-luyet: Employee; Boehringer Ingelheim International GmbH, Other Relationship; IQVIA Inc., Sanofi. S.F.Fazeli farsani: Employee; Boehringer Ingelheim International GmbH. L.Koeneman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Diabetes is associated with an increased risk of kidney stones. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) might lower the risk of nephrolithiasis, as they increase urinary flow. However, a prior meta-analysis was inconclusive, and only one Danish study reported a lower risk of kidney stones. We investigated the association between SGLT2i use and the risk of nephrolithiasis in routine practice. Using claims data from 2 private health plans and Medicare (2013-2020) , we identified 331,028 pairs of 1:1 propensity score-matched adults with type 2 diabetes (T2D) initiating an SGLT2i or a DPP4 inhibitor (DPP4i) , and 358,203 pairs initiating an SGLT2i or a GLP1 receptor agonist (GLP1RA) . Our primary outcome was nephrolithiasis diagnosed by ICD codes in the inpatient or outpatient setting. We estimated hazard ratios (HRs) , rate differences (RD) and 95% confidence intervals (CI) , adjusting for 57 baseline covariates in the PS model. Over a mean follow-up of ∼months on treatment, the risk of nephrolithiasis was lower in the SGLT2i group compared with the DPP4i group (HR 0.74 [95%CI 0.71-0.77]; RD 4.0 [95%CI, -4.6, -3.4]) or the GLP1RA group (HR 0.69 [95%CI 0.67-0.72]; RD -4.1 [95%CI, -4.7, -3.5]) (Table) . Secondary definitions of the outcome based on a hospital discharge diagnosis produced consistent results. In routine care, SGLT2i use was associated with a reduced risk of nephrolithiasis, compared to DPP4i or GLP1RA use in patients with T2D. Disclosure J.M.Paik: None. H.Tesfaye: None. G.Curhan: Employee; OM1, Inc, Other Relationship; UpToDate. J.M.Mastrorilli: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute.

ImportanceSodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy has been associated with cardiovascular benefits and a few adverse events; however, whether the comparative effectiveness and safety profiles vary with differences in baseline hemoglobin A1c (HbA1c) levels is unknown.ObjectiveTo compare cardiovascular effectiveness and safety of treatment with SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP-4i) in adults with type 2 diabetes (T2D) (1) overall and (2) at varying baseline HbA1c levels.Design, Setting, and ParticipantsA new-user comparative effectiveness and safety research study was conducted among 144 614 commercially insured adults, initiating treatment with SGLT2i or DPP-4i and with a recorded T2D diagnosis at baseline and at least 1 HbA1c laboratory result recorded within 3 months before treatment initiation.InterventionsThe intervention consisted of the initiation of treatment with SGLT2i or DPP-4i.Main Outcomes and MeasuresPrimary outcomes were a composite of myocardial infarction, stroke, or all-cause death (modified major adverse cardiovascular events [MACE]) and hospitalization for heart failure (HHF). Safety outcomes were hypovolemia, fractures, falls, genital infections, diabetic ketoacidosis (DKA), acute kidney injury (AKI), and lower-limb amputation. Incidence rate (IR) per 1000 person-years, hazard ratios (HR) and rate differences (RD) with their 95% CIs were estimated controlling for 128 covariates.ResultsA total of 144 614 eligible adults (mean [SD] age, 62 [12.4] years; 54% male participants) with T2D initiating treatment with a SGLT2i (n = 60 523) or a DPP-4i (n = 84 091) were identified; 44 099 had an HbA1c baseline value of less than 7.5%, 52 986 between 7.5% and 9%, and 47 529 greater than 9%. Overall, 87 274 eligible patients were 1:1 propensity score–matched: 24 052 with HbA1c less than 7.5%; 32 290 with HbA1c between 7.5% and 9%; and 30 932 with HbA1c greater than 9% (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01). The initiation of SGLT2i vs DPP-4i was associated with a reduction in the risk of modified MACE (IR per 1000 person-years 17.13 vs 20.18, respectively; HR, 0.85; 95% CI, 0.75-0.95; RD, −3.02; 95% CI, −5.23 to –0.80) and HHF (IR per 1000 person-years 3.68 vs 8.08, respectively; HR, 0.46; 95% CI, 0.35 to 0.57; RD −4.37; 95% CI, −5.62 to −3.12) over a mean follow-up of 8 months, with no evidence of treatment effect heterogeneity across the HbA1c levels. Treatment with SGLT2i showed an increased risk of genital infections and DKA and a reduced AKI risk compared with DPP-4i. Findings were consistent by HbA1c levels, except for a more pronounced risk of genital infections associated with SGLT2i for HbA1c levels of 7.5% to 9% (IR per 1000 person-years 68.5 vs 22.8, respectively; HR, 3.10; 95% CI, 2.68-3.58; RD, 46.22; 95% CI, 40.54-51.90).Conclusions and RelevanceIn this comparative effectiveness and safety research study among adults with T2D, SGLT2i vs DPP-4i treatment initiators had a reduced risk of modified MACE and HHF, an increased risk of genital infections and DKA, and a lower risk of AKI, regardless of baseline HbA1c.

OBJECTIVE Diabetes and obesity are highly prevalent among hospitalized patients with coronavirus disease 2019 (COVID-19), but little is known about their contributions to early COVID-19 outcomes. We tested the hypothesis that diabetes is a risk factor for poor early outcomes, after adjustment for obesity, among a cohort of patients hospitalized with COVID-19. RESEARCH DESIGN AND METHODS We used data from the Massachusetts General Hospital (MGH) COVID-19 Data Registry of patients hospitalized with COVID-19 between 11 March 2020 and 30 April 2020. Primary outcomes were admission to the intensive care unit (ICU), need for mechanical ventilation, and death within 14 days of presentation to care. Logistic regression models were adjusted for demographic characteristics, obesity, and relevant comorbidities. RESULTS Among 450 patients, 178 (39.6%) had diabetes—mostly type 2 diabetes. Among patients with diabetes versus patients without diabetes, a higher proportion was admitted to the ICU (42.1% vs. 29.8%, respectively, P = 0.007), required mechanical ventilation (37.1% vs. 23.2%, P = 0.001), and died (15.9% vs. 7.9%, P = 0.009). In multivariable logistic regression models, diabetes was associated with greater odds of ICU admission (odds ratio 1.59 [95% CI 1.01–2.52]), mechanical ventilation (1.97 [1.21–3.20]), and death (2.02 [1.01–4.03]) at 14 days. Obesity was associated with greater odds of ICU admission (2.16 [1.20–3.88]) and mechanical ventilation (2.13 [1.14–4.00]) but not with death. CONCLUSIONS Among hospitalized patients with COVID-19, diabetes was associated with poor early outcomes, after adjustment for obesity. These findings can help inform patient-centered care decision making for people with diabetes at risk for COVID-19.

OBJECTIVE We evaluated the effect of optimizing metformin dosing on glycemia and body weight in type 2 diabetes. RESEARCH DESIGN AND METHODS This was a prespecified analysis of 6,823 participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) taking metformin as the sole glucose-lowering drug who completed a 4- to 14-week (mean ± SD 7.9 ± 2.4) run-in in which metformin was adjusted to 2,000 mg/day or a maximally tolerated lower dose. Participants had type 2 diabetes for RESULTS Adjusted for duration of run-in, the mean ± SD change in HbA1c was −0.65 ± 0.02% (−7.1 ± 0.2 mmol/mol) when the dose was increased by ≥1,000 mg/day, −0.48 ± 0.02% (−5.2 ± 0.2 mmol/mol) when the dose was unchanged, and −0.23 ± 0.07% (−2.5 ± 0.8 mmol/mol) when the dose was decreased (n = 2,169, 3,548, and 192, respectively). Higher HbA1c at entry predicted greater reduction in HbA1c (P < 0.001) in univariate and multivariate analyses. Weight loss adjusted for duration of run-in averaged 0.91 ± 0.05 kg in participants who increased metformin by ≥1,000 mg/day (n = 1,894). CONCLUSIONS Optimizing metformin to 2,000 mg/day or a maximally tolerated lower dose combined with emphasis on medication adherence and lifestyle can improve glycemia in type 2 diabetes and HbA1c values ≥6.8% (51 mmol/mol). These findings may help guide efforts to optimize metformin therapy among persons with type 2 diabetes and suboptimal glycemic control.

OBJECTIVE There is a paucity of data evaluating recent changes in clinical and prescriber characteristics of patients initiating sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA). RESEARCH DESIGN AND METHODS U.S.-based administrative claims data (July 2013 to June 2018) were used to identify initiators of SGLT2i and GLP-1RA. RESULTS Over 5 years, empagliflozin initiation (as a proportion of SGLT2i) increased by 57.1% (P < 0.001 for trend), while canagliflozin initiation declined by 75.1% (P < 0.001). Empagliflozin was the only agent within SGLT2i with an increase in the proportion of patients with myocardial infarction, stroke, or heart failure (collectively called CVD-HF) (P < 0.001). Liraglutide initiation (as a proportion of total GLP-1RA) declined by 32.1% (P < 0.001), and dulaglutide initiation increased by 34.1% (P < 0.001); the proportion of patients with CVD-HF increased the most in liraglutide initiators (5.1% increase; P < 0.001). Most prescribers were internists or endocrinologists; cardiologist prescribing remained low ( CONCLUSIONS For SGLT2i, shifts in preference for empagliflozin followed changes in drug labels and guidelines, while for GLP-1RA, other factors such as price or ease of administration may have led to a preference for dulaglutide over liraglutide.

Background: Physical activity among those with type 2 diabetes (T2D) is independently associated with superior medical outcomes, but existing behavioral interventions have not led to widespread increases in activity in this population. A remotely delivered intervention that targets well-being constructs associated with greater activity and assists in the creation of specific physical activity goals has the potential to improve activity and outcomes in T2D. Objective: To outline the rationale and methods of two studies designed to assess the impact and optimal duration of a combined positive psychology-motivational interviewing (PP-MI) intervention for inactive persons with T2D. Methods: We conducted trials studying 8-week (BEHOLD-8;) and 16-week (BEHOLD-16;) phone-delivered interventions, compared to attention-matched control conditions. In a two-step randomization design, participants were allocated randomly first to study (BEHOLD-8 or BEHOLD-16), then to study condition within study. The primary aims in both trials were feasibility (rates of session completion) and acceptability (participant session ratings), with additional aims examining intervention effects on accelerometer-measured physical activity, psychological measures, and health-related metrics (e.g. vital signs). Main analyses, currently being conducted, will utilize mixed effects models between study conditions, and secondary analyses will utilize the same models to compare the 8- and 16-week PP-MI interventions on feasibility and impact. Results: Enrollment and data collection have been completed for both trials (BEHOLD-8: N = 60; BEHOLD-16: N = 70), and data analysis is ongoing to assess feasibility and acceptability within study, as well as the relative feasibility and acceptability of the PP-MI interventions across the two studies. We will also explore impact on clinical outcomes between groups. Conclusions: This design will address how intervention content (i.e. PP elements vs. no PP elements) and intervention duration (8 weeks vs. 16 weeks) affect feasibility, acceptability, and impact, allowing intervention optimization before a next-step larger clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03150199; NCT03001999.

Objective We aimed to understand the factors associated with SGLT2i adherence and longitudinal adherence trajectories in older adults with type 2 diabetes. Research Design and Methods Using Medicare claims data (April 2013-December 2017), we identified 83,675 new SGLT2i users aged ≥66 years old with type 2 diabetes. We measured SGLT2i adherence as the Proportion of Days Covered (PDC) during the first year of SGLT2i therapy. We used linear regression to assess the association between baseline covariates and PDC. Then we used group-based trajectory modeling to identify distinct longitudinal SGLT2i adherence groups and used a multivariable logistic regression model to examine the association between baseline covariates and membership in these adherence groups. Results Unadjusted mean PDC was 63%. Previous adherence to statins had the strongest positive association with PDC [regression coefficient 6.00% (95% CI, 5.50%,6.50%)], whereas female sex [-5.51% (-6.02%, -5.00%)], and Black race/ethnicity [-5.06% (-6.03%, -4.09%)] had the strongest negative association. We identified three adherence trajectory groups: low (23% of patients, mean PDC: 17%), moderate (32%, mean PDC: 50%), or high adherence (45%, mean PDC 96%). More patients in the high adherence group were previously adherent to statins [OR 1.43 (95% CI 1.39,1.48)], and more women [1.28 (1.23,1.32)] and Black patients [1.31 (1.23,1.40)] were in the low adherence group. Conclusions In a large population of older patients with type 2 diabetes, 45% were highly adherent during the first year of SGLT2i treatment. Female sex and Black race/ethnicity were most strongly associated with low adherence.

Food insecurity is associated with worse glycemic management for individuals with type 2 diabetes mellitus (T2DM), but whether medically tailored meals (MTM), a food insecurity intervention, can improve glycemic management is unclear.To describe the protocol for a trial assessing whether an MTM plus lifestyle intervention improves hemoglobin A1c (HbA1c) and participant-reported outcomes, relative to a food subsidy (money that can be spent on foods participants choose), for adults with both T2DM and food insecurity.The Food as Medicine for Diabetes (FAME-D) randomized clinical trial (goal n = 200) is a pragmatic trial with an active comparator. Participants, who will have T2DM and report food insecurity, will be randomly assigned to a 6-month MTM plus telephone-delivered lifestyle change intervention, or a 6-month food subsidy ($40/month). The primary outcome is HbA1c at 6 months. Secondary outcomes include HbA1c at 12 months to assess whether the intervention effect (if any) is sustained, along with weight, food insecurity, diabetes distress, and health-related quality of life. Qualitative analyses of semi-structured interviews will help understand why, how, and under what circumstances the intervention achieved its observed results.Results from FAME-D will help inform clinical management of food insecurity when it co-occurs with T2DM. Further, results may be useful as healthcare payors are considering coverage for MTM interventions.gov: NCT04828785.

Background: Most individuals with type 2 diabetes (T2D) struggle to adhere to one or more health behaviors. Text message interventions (TMIs) have the potential to improve adherence but have had mixed effects on diet and activity in T2D. We developed an eight-week, adaptive, algorithm-driven TMI to promote physical activity, diet, self-care, and well-being. Then, in a single-arm trial, we assessed its feasibility, acceptability, and preliminary efficacy in 15 individuals with T2D and suboptimal adherence. Methods: Participants received daily text messages and were asked to rate the utility of each message (0=not helpful, 10=very helpful). These ratings were used by an algorithm to select subsequent messages based on each participant’s prior ratings. We assessed intervention feasibility by rates of message transmission/response and acceptability through ratings of message utility and burden. Finally, we examined pre-post changes in diabetes self-care, diet, physical activity, and psychological outcomes and calculated effect sizes (Cohen’s d). Results: All text messages were delivered, and participants provided ratings for 79% of messages, above our a priori thresholds for feasibility. Participants rated the individual messages and overall TMI as subjectively useful (utility: 8.1 [SD=2.1] and 7.8 [SD=2.0], respectively) and not burdensome (burden: 0.8 [SD=1.8]). The intervention led to significant, medium- to large-sized improvements in self-care ( d=0.77), diet ( d=0.99), and activity ( d=0.61) but minimal change in psychological outcomes. Conclusions: The TMI was feasible and well-accepted, and it led to promising improvements in adherence-related outcomes. These findings should be confirmed in a larger randomized controlled trial.

Context The clinical utility and implications of continuous glucose monitoring (CGM) in cystic fibrosis (CF) are unclear. Objective We examined the correlation between CGM measures and clinical outcomes in adults with CF, investigated the relationship between hemoglobin A1c (HbA1c) and CGM-derived average glucose (AG), and explored CGM measures that distinguish cystic fibrosis–related diabetes (CFRD) from normal and abnormal glucose tolerance. Methods This prospective observational study included 77 adults with CF who had CGM and HbA1c measured at 2 to 3 time points 3 months apart. Results Thirty-one of the 77 participants met American Diabetes Association–recommended diagnostic criteria for CFRD by oral glucose tolerance testing and/or HbA1c. In all participants, CGM measures of hyperglycemia and glycemic variability correlated with nutritional status and pulmonary function. HbA1c was correlated with AG (R2 = 0.71, P < 0.001), with no significant difference between this regression line and that previously established in type 1 and type 2 diabetes and healthy volunteers. Cutoffs of 17.5% time > 140 mg/dL and 3.4% time > 180 mg/dL had sensitivities of 87% and 90%, respectively, and specificities of 95%, for identifying CFRD. Area under the curve and percent of participants correctly classified with CFRD were higher for AG, SD, % time > 140, > 180, and > 250 mg/dL than for HbA1c. Conclusion CGM measures of hyperglycemia and glycemic variability are superior to HbA1c in distinguishing those with and without CFRD. CGM-derived AG is strongly correlated with HbA1c in adults with CF, with a similar relationship to other diabetes populations. Future studies are needed to investigate CGM as a diagnostic and screening tool for CFRD.

Objective Over 99% of the EMPA-REG OUTCOME trial participants had established cardiovascular disease (CVD). We aimed to investigate effectiveness and safety outcomes among patients with type 2 diabetes (T2D) initiating empagliflozin vs dipeptidyl peptidase-4 inhibitor (DPP-4i) across the broad spectrum of cardiovascular risk. Methods In a population-based cohort study we identified 39,072 pairs of 1:1 propensity score-matched adult patients with T2D initiating empagliflozin or DPP-4i, using data from 2 U.S. commercial insurance databases and Medicare between 08/2014-09/2017. Primary outcomes were a composite of myocardial infarction (MI)/stroke, and hospitalization for heart failure (HHF). Safety outcomes were bone fractures, lower-limb amputations (LLA), diabetic ketoacidosis (DKA), and acute kidney injury (AKI). We estimated pooled hazard ratios (HR) and 95% CI adjusting for >140 baseline covariates. Results Study participants had mean age of 60 years and only 28% had established CVD. Compared to DPP-4i, empagliflozin was associated with similar risk of MI/stroke [HR (95% CI), 0.99 (0.81-1.21)], and lower risk of HHF [0.48 (0.35-0.67) and 0.63 (0.54-0.74), based on a primary and any HF discharge diagnosis, respectively]. The HR was 0.52 (0.38-0.72) for all-cause mortality (ACM) and 0.83 (0.70-0.98) for a composite of MI/stroke/ACM. Empagliflozin was associated with a similar risk of LLA and fractures, an increased risk of DKA [1.71 (1.08-2.71)], and a decreased risk of AKI [0.60 (0.43-0.85)]. Conclusions In clinical practice, the initiation of empagliflozin vs DPP-4i was associated with a lower risk of HHF, ACM, and MI/stroke/ACM, a similar risk of MI/stroke, and a safety profile consistent with documented information. This article is protected by copyright. All rights reserved.