Effects of dipeptidyl peptidase-4 inhibitors and sulphonylureas on cognitive and physical function in nursing home residents.

AIMS: Dipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycaemia-mediated declines in cognitive and physical functioning compared with sulphonylureas (SUs), yet comparative studies are unavailable among older adults, particularly nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents. MATERIALS AND METHODS: This new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after 1:1 propensity score matching using Cox regression models. RESULTS: The matched cohort (N = 1784) had a mean ± SD age of 80 ± 8 years and 73% were women. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared with SU users, DPP4I users had lower 180-day rates of cognitive decline [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.31-1.19], altered mental status events (HR = 0.71, 95% CI 0.39-1.27), and functional decline (HR = 0.89, 95% CI 0.51-1.56), but estimates were imprecise. CONCLUSIONS: Rates of cognitive and functional decline may be reduced among older NH residents using DPP4Is compared with SUs, but larger studies with greater statistical power should resolve the remaining uncertainty by providing more precise effect estimates.

INSULIN GLARGINE 300 U/ML IS ASSOCIATED WITH LESS WEIGHT GAIN WHILE MAINTAINING GLYCEMIC CONTROL AND LOW RISK OF HYPOGLYCEMIA COMPARED WITH INSULIN GLARGINE 100 U/ML IN AN AGING POPULATION WITH TYPE 2 DIABETES.

OBJECTIVE: Assess efficacy, hypoglycemia, and weight gain in patients with type 2 diabetes (T2D) treated with insulin glargine 300 U/mL (Gla-300) or 100 U/mL (Gla-100) across different age groups. METHODS: Pooled data were generated for patients randomized to Gla-300 or Gla-100 in the EDITION 2 (NCT01499095) and 3 (NCT01676220) studies. In 4 age groups (<55, ≥55 to <60, ≥60 to <65, ≥65 years), glycated hemoglobin A1C (A1C), percentage of patients reaching A1C <7.5% (58 mmol/mol), weight change, confirmed hypoglycemia (blood glucose ≤70 mg/dL), and/or severe hypoglycemia (events requiring third-party assistance) were analyzed with descriptive statistics and logistic, binomial, and analysis of covariance regression modeling. RESULTS: A1C reductions from baseline and proportions of patients at target were similar for Gla-300 and Gla-100 across all age groups at 6 and 12 months, but hypoglycemia incidence and event rate were lower with Gla-300 at 6 (both P<.001) and 12 months ( P<.001 and P = .005, respectively). Patients on Gla-300 gained less weight than those on Gla-100 at 6 ( P = .027) and 12 months ( P = .021). Changes in weight and daily weight-adjusted insulin dose decreased with increasing age at 6 ( P<.001 and P = .017, respectively) and 12 months ( P<.001 and P = .011, respectively). CONCLUSION: Older patients with T2D may benefit from treatment with Gla-300, which is associated with a lower hypoglycemia rate and less weight gain with similar efficacy compared with Gla-100. ABBREVIATIONS: A1C = glycated hemoglobin A1C BMI = body mass index Gla-100 = insulin glargine 100 U/mL Gla-300 = insulin glargine 300 U/mL OAD = oral antidiabetes drug T2D = type 2 diabetes.

Diabetes Management in the Elderly.

IN BRIEF Older adults with diabetes present unique challenges and require considerations that are not traditionally associated with diabetes management. In this review, we focus on issues that are unique to the older population and provide practical guidance for clincians who care for them.

Diabetes in long-term care facilities.

With the aging of the population and longer life expectancies, the prevalence of population with multiple chronic medical conditions has increased. Difficulty managing these conditions as people age (because of changes in physical, functional, or cognitive abilities and the complexity of many treatment regimens), has led to more individuals with multiple medical conditions admitted to the long-term care facilities. Older adults with diabetes residing in the long-term facilities represent the most vulnerable of this cohort. Studies that specifically target diabetes management in older population are lacking and those that target diabetes management in the long-term care facilities are even fewer. The lack of knowledge regarding the care of the elderly residing in long-term care with diabetes may lead to treatment failure and higher risk of hyperglycemia, as well as hypoglycemia. In aging populations, hypoglycemia has the potential for catastrophic consequences. To avoid this, the management of older population with diabetes and other medical comorbidities residing in long-term care facilities requires a more holistic approach compared with focusing on individual chronic disease goal achievement.

Dynamical glucometry: use of multiscale entropy analysis in diabetes.

Diabetes mellitus (DM) is one of the world's most prevalent medical conditions. Contemporary management focuses on lowering mean blood glucose values toward a normal range, but largely ignores the dynamics of glucose fluctuations. We probed analyte time series obtained from continuous glucose monitor (CGM) sensors. We show that the fluctuations in CGM values sampled every 5 min are not uncorrelated noise. Next, using multiscale entropy analysis, we quantified the complexity of the temporal structure of the CGM time series from a group of elderly subjects with type 2 DM and age-matched controls. We further probed the structure of these CGM time series using detrended fluctuation analysis. Our findings indicate that the dynamics of glucose fluctuations from control subjects are more complex than those of subjects with type 2 DM over time scales ranging from about 5 min to 5 h. These findings support consideration of a new framework, dynamical glucometry, to guide mechanistic research and to help assess and compare therapeutic interventions, which should enhance complexity of glucose fluctuations and not just lower mean and variance of blood glucose levels.

Impact of a tubeless, disposable insulin pump on emergency department visits and inpatient admissions among a Medicare population.

BACKGROUND: A tubeless, disposable insulin pump (Omnipod DASH Insulin Management System, Insulet Corporation) has demonstrated improved glycemic outcomes for people with diabetes who require insulin. The impact of the system on downstream health care events has not been studied. OBJECTIVE: To assess health care resource utilization for a Medicare population before and after starting tubeless, disposable insulin pump therapy. METHODS: This retrospective, observational analysis used data from the Centers for Medicare & Medicaid Services 100% Research Identifiable Files. Study outcomes included change in event rates for diabetes-related emergency department (DRED) visits, all-cause emergency department (ACED) visits, diabetes-related inpatient (DRIP) admissions, and all-cause inpatient (ACIP) admissions among Medicare beneficiaries who started the tubeless, disposable insulin pump in 2020 (postpump observation period) as compared with the same duration and calendar period in 2019 (prepump observation period) with no pump use. Subgroup analyses were performed based on Medicare entitlement reason, diabetes type, and diagnosis status for depressive disorder. RESULTS: A total of 811 users met the criteria for analysis: 46.2% had type 2 diabetes, a majority (59.2%) were aged 65 years or older, and 37.0% had a diagnosis for depressive disorder. Significant reductions were observed for DRED of -46.9% (95% CI = -63% to -23%); ACED of -29.0% (95% CI = -37% to -20%); ACIP of -19.9% (95% CI = -32% to -6%). DRIP rates declined notably (-36.6%; 95% CI = -61% to 4%). Event rates observed across subgroups demonstrated consistent downward trends; however, not all were statistically significant. CONCLUSIONS: These findings demonstrate that use of the tubeless, disposable insulin pump was associated with reductions in DRED, ACED, and ACIP. Our results provide real-world evidence to support the use of the tubeless, disposable insulin pump among Medicare beneficiaries who require insulin, regardless of diabetes type or Medicare entitlement reason. Additional studies are recommended to further evaluate the effect of insulin pumps on health care utilization among the Medicare population and other insurance populations.

Continuous Glucose Monitoring Use in Older Adults for Optimal Diabetes Management.

More than one third of U.S. adults age ≥65 years have diabetes. According to early studies, 61% of all diabetes-related costs in the United States were for individuals age ≥65 years, and more than half of these costs attributable to treating diabetes-related complications. Numerous studies have shown that use of continuous glucose monitoring (CGM) has been shown to improve glycemic control and reduce the incidence and severity of hypoglycemia in younger adults with type 1 diabetes and insulin-treated type 2 diabetes (T2D), and there is growing evidence demonstrating the same benefits in older T2D populations. However, because older adults with diabetes are a heterogeneous group with variable clinical, functional, and psychosocial milieu, clinicians must consider whether each patient can use CGM and, if so, the type of CGM device best addresses each patient's needs and capabilities. This article reviews the evidence supporting CGM in the older population, discusses the barriers and benefits of CGM use in older adults with diabetes, and provides recommendations for how different types of CGM systems can be used strategically to improve glycemic control, reduce hypoglycemia, decrease the burden of diabetes, and improve quality of life.

Geriatric Syndromes in Older Adults with Diabetes.

Over one-quarter of adults ≥65 years old have diabetes in the United States. Guidelines recommend individualization of glycemic targets in older adults with diabetes as well as implementing treatment strategies that minimize risk for hypoglycemia. Patient-centered management decisions should be informed by comorbidities, the individual's capacity for self-care, and the presence of key geriatric syndromes that may impact self-management and patient safety. Key geriatric syndromes include cognitive impairment, depression, functional impairments (eg, vision, hearing, and mobility challenges), falls and fractures, polypharmacy, and urinary incontinence. Screening for geriatric syndromes in older adults is recommended to inform treatment strategies and optimize outcomes.

Adoption of sodium-glucose cotransporter-2 inhibitors among prescribers caring for nursing home residents.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitor (SGLT2I) use has increased among community-dwelling populations, but little is known about how clinicians have prescribed them for US nursing home (NH) residents. We described the adoption of SGLT2Is by prescribers caring for long-stay NH residents by clinician specialty and over time, compared with sulfonylureas, an older diabetes medication class. METHODS: We conducted a retrospective cohort study of prescribers of SGLT2Is and sulfonylureas for all long-stay US NH residents aged 65 years or older (2017-2019). Using 100% of Medicare Part D claims linked to prescriber characteristics data, we identified all dispensings of SGLT2Is and sulfonylureas for long-stay NH residents and their associated prescribers. We described the distribution of prescriber specialties for each drug class over time as well as the number of NH residents prescribed SGLT2s versus sulfonylureas. We estimated the proportions of prescribers who prescribed both drug classes versus only sulfonylureas or only SGLT2Is. RESULTS: We identified 36,427 unique prescribers (SGLT2I: N = 5811; sulfonylureas: N = 35,443) for 117,667 NH residents between 2017 and 2019. For both classes, family medicine and internal medicine physicians accounted for most prescriptions (75%-81%). Most clinicians (87%) prescribed only sulfonylureas, 2% prescribed SGLT2Is only, and 11% prescribed both. Geriatricians were least likely to prescribe only SGLT2Is. We observed an increase in the number of residents with SGLT2I use from n = 2344 in 2017 to n = 5748 in 2019. CONCLUSIONS: Among NH residents, most clinicians have not incorporated SGLT2Is into their prescribing for diabetes, but the extent of use is increasing. Family medicine and internal medicine physicians prescribed the majority of diabetes medications for NH residents, and geriatricians were the least likely to prescribe only SGLT2Is. Future research should explore provider concerns regarding SGLT2I prescribing, particularly adverse events.

Comparative safety of sulfonylureas among U.S. nursing home residents.

BACKGROUND: The comparative safety of sulfonylureas (SUs) in nursing home (NH) residents remains understudied despite widespread use. We compared the effects of three SU medications and initial SU doses on adverse glycemic and cardiovascular events among NH residents. METHODS: This national retrospective cohort study linked Medicare claims with Minimum Data Set 2.0 assessments for long-stay NH residents aged ≥65 years between January 2008 and September 2010. Exposures were the SU medication initiated (glimepiride, glipizide, or glyburide) and doses (standard or reduced). One-year outcomes were hospitalizations or emergency department visits for severe hypoglycemia, heart failure (HF), stroke, and acute myocardial infarction (AMI). After the inverse probability of treatment and inverse probability of censoring by death weighting, we estimated hazard ratios (HR) using Cox regression models with robust 95% confidence intervals (CI). RESULTS: The cohort (N = 6821) included 3698 new glipizide, 1754 glimepiride, and 1369 glyburide users. Overall, the mean (standard deviation) age was 81.4 (8.2) years, 4816 (70.6%) were female, and 5164 (75.7%) were White non-Hispanic residents. The rates of severe hypoglycemia were 30.3 (95% CI 22.3-40.1), 49.0 (95% CI 34.5-67.5), and 35.9 (95% CI 22.2-54.9) events per 1000 person-years among new glipizide, glimepiride, and glyburide users, respectively (glimepiride versus glipizide HR 1.6, 95% CI 1.0-2.4, p = 0.04; glyburide versus glipizide HR 1.2, 95% CI 0.7-1.9, p = 0.59). The rates of severe hypoglycemia were 27.1 (95% CI 18.6-38.0) and 42.8 (95% CI 33.6-53.8) events per 1000 person-years among new users of reduced and standard SU doses, respectively (HR 2.2, 95% CI 1.4-3.5, p < 0.01). Rates of HF, stroke, and AMI were similar between medications and doses. CONCLUSIONS: Among long-stay NH residents, new use of glimepiride and standard SU doses resulted in higher rates of severe hypoglycemic events. Cardiovascular outcomes may not be affected by the choice of SU medication or dose.

An Examination of Whether Diabetes Control and Treatments Are Associated With Change in Frailty Index Across 8 Years: An Ancillary Exploratory Study From the Action for Health in Diabetes (Look AHEAD) Trial.

OBJECTIVE: The aim of this study was to describe cross-sectional and longitudinal associations between glycated hemoglobin (HbA1c) levels and strategies to control type 2 diabetes with baseline levels and 8-year changes in a deficit accumulation frailty index (FI), a commonly used marker of biological aging. RESEARCH DESIGN AND METHODS: We conducted exploratory analyses from 4,169 participants, aged 45-76 years, who were followed in the Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial, pooling data across intervention groups. We related baseline and 8-year levels of HbA1c with FI scores using analyses of variance and covariance. Associations between 8-year changes in FI and the use of diabetes medication classes and weight changes were assessed with control for HbA1c levels. Inverse probability weighting was used to assess bias associated with differential follow-up. RESULTS: Baseline and average HbA1c levels over time of <7%, as compared with ≥8%, were associated with less increase in FI scores over 8 years (both P ≤ 0.002). After adjustment for HbA1c, use of metformin and weight loss >5% were independently associated with slower increases in frailty. CONCLUSIONS: Lower HbA1c levels among individuals with diabetes are associated with slower biological aging as captured by a deficit accumulation FI. Strategies to control diabetes through weight loss or metformin use may also slow aging.

Treatment of type 2 diabetes in the elderly.

As the number of older adults increases in the United States and worldwide, management of patients with multiple coexisting chronic diseases has become a critical component in health care. Management of diabetes is particularly challenging in this population due to significant risks of microvascular and macrovascular diseases on the one hand, and complications of the treatment strategies (e.g., hypoglycemia) with intensive control on the other hand. To provide a balanced approach to diabetes in the elderly, a comprehensive and holistic strategy, with consideration of overall health, functional status, psychosocial environment, financial resources and, finally but most importantly, quality of life is needed. Understanding the unique challenges faced by older adults with diabetes and issues pertaining to antidiabetes medications with aging is an important first step in the direction of better and tailored care of this burgeoning population.

Defining Minimum Necessary Communication During Care Transitions for Patients on Antihyperglycemic Medication: Consensus of the Care Transitions Task Force of the IPRO Hypoglycemia Coalition.

INTRODUCTION: Antihyperglycemic agents are significant contributors to adverse drug events, responsible for emergency department visits, hospitalizations, and death. Nationally, the rate of serious hypoglycemic events associated with these agents remains high despite widespread efforts to improve drug safety. Transitions of care between healthcare settings can lead to communication challenges between care professionals and increase the risk of adverse drug events. System-based improvements are needed to assure the safe transitions for patients with diabetes who are on antihyperglycemic agents. The objective of this study was to develop a consensus list of requisite elements that should be communicated between care settings during transitions of patients who are prescribed antihyperglycemic agents. METHODS: The Island Peer Review Organization (IPRO) Hypoglycemia Coalition identified suboptimal transitions of care as a barrier to improving patient safety and quality of diabetes care. The Coalition formed a multidisciplinary Task Force with experts in the field of diabetes care. The Task Force created a draft list of requisite communication elements through literature review and deliberation on monthly conference calls. A blinded iterative Delphi process was subsequently performed to generate a consensus list of requisite communication elements that participating experts agreed were necessary to safely and effectively assume the management of patients with diabetes upon care transitions. RESULTS: The Task Force completed a series of four iterative polls from September 2015 to August 2016, resulting in a final list of 22 requisite communication elements (the Diabetes Management Discharge Communication List), with the elements conceptually categorized into three domains: diagnosis and treatment, factors affecting glycemic control or patient risk, and patient self-management. CONCLUSIONS: The Diabetes Management Discharge Communication List provides an initial framework for the development of diabetes-specific resources to improve clinical communication between care settings.

A Successful Diabetes Management Model of Care in Long-Term Care Facilities.

The management of diabetes in long-term care (LTC) facilities requires facility staff to perform most self-care activities on the behalf of the residents. A practical model of care to improve diabetes management was developed and implemented at 6 LTC facilities in the Northeast United States between 2009 and 2012. The components of the program included (1) developing an individualized education curriculum and educating LTC interdisciplinary staff; (2) educating patients and caregivers; and (3) developing a clinical care algorithm. Over 500 staff members were educated and achieved competence. There were 1031 residents screened for risk of hypo- or hyperglycemia on admission, and 245 residents (24%) experienced hypoglycemia and 240 residents (23%) experienced hyperglycemia. Hypoglycemia episodes resolved without recurrence in 73%-90% cases because of interventions initiated by LTC staff. The implementation of a practical model of diabetes management in LTC facilities can improve staff education and lead to improved diabetes management.

Comparative safety of dipeptidyl peptidase-4 inhibitors and sulfonylureas among frail older adults.

BACKGROUND: Studies comparing dipeptidyl peptidase-4 inhibitors (DPP4Is) to sulfonylureas (SUs) are unavailable for frail older adults, especially nursing home (NH) residents. We examined the effects of DPP4Is versus SUs on severe adverse glycemic events, cardiovascular events, and death among NH residents. METHODS: We conducted a national retrospective cohort study of long-stay NH residents aged ≥65 years using 2008-2010 national US Minimum Data Set clinical assessment data and linked Medicare claims. Exposure was new DPP4I versus new SU use assessed via Medicare Part D drug claims. One-year outcomes were severe hypoglycemia, severe hyperglycemia, acute myocardial infarction (AMI), heart failure (HF), major adverse cardiovascular events plus HF (MACE+HF), and death. We compared outcomes after propensity score matching using Cox proportional hazards regression models. RESULTS: The cohort (N = 2016) had a mean (SD) age of 81 (8.1) years and was 72% female. Compared with SU users, DPP4I users had a lower 1-year rate of severe hypoglycemic events (HR = 0.57, 95% CI 0.34-0.94), but statistically similar rates of severe hyperglycemic events (HR = 0.94, 95% CI 0.52-1.72), AMI (HR = 0.76, 95% CI 0.44-1.30), HF (HR = 1.01, 95% CI 0.79-1.30), MACE+HF (HR = 0.90, 95% CI 0.72-1.12), and death (HR = 0.97, 95% CI 0.86-1.10). CONCLUSIONS: DPP4Is should be a preferred treatment option over SUs for NH residents and other frail older adults given the importance of avoiding hypoglycemia.

Comparative Effectiveness and Safety of Sodium-Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults.

OBJECTIVE: Both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in randomized controlled trials of patients with type 2 diabetes (T2D) generally <65 years old and mostly with cardiovascular disease. We aimed to evaluate the comparative effectiveness and safety of SGLT2i and GLP-1RA among real-world older adults. RESEARCH DESIGN AND METHODS: Using Medicare data (April 2013-December 2016), we identified 90,094 propensity score-matched (1:1) T2D patients ≥66 years old initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE) (i.e., myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections, fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections, and overall mortality. We estimated hazard ratios (HRs) and rate differences (RDs) per 1,000 person-years, controlling for 140 baseline covariates. RESULTS: Compared with GLP-1RA, SGLT2i initiators had similar MACE risk (HR 0.98 [95% CI 0.87, 1.10]; RD -0.38 [95% CI -2.48, 1.72]) and reduced HHF risk (HR 0.68 [95% CI 0.57, 0.80]; RD -3.23 [95% CI -4.68, -1.77]), over a median follow-up of ∼6 months. They also had 0.7 more DKA events (RD 0.72 [95% CI 0.02, 1.41]), 0.9 more LLA (RD 0.90 [95% CI 0.10, 1.70]), 57.1 more genital infections (RD 57.08 [95% CI 53.45, 60.70]), and 7.1 fewer AKI events (RD -7.05 [95% CI -10.27, -3.83]) per 1,000 person-years. CONCLUSIONS: Among older adults, those taking SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and genital infections versus those taking GLP-1RA.

Changes in mood and health-related quality of life in Look AHEAD 6 years after termination of the lifestyle intervention.

OBJECTIVE: The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group [DSE]) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012. METHODS: A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured. RESULTS: ILI participants and DSE participants lost 3.1 (0.3) and 3.8 (0.3) kg [represented as mean (SE); p = 0.10], respectively, during the 6-year postintervention follow-up. No significant differences were observed between groups during this time in incident mild or greater symptoms of depression, antidepressant medication use, or in changes on the physical component summary or mental component summary scores of the Short Form-36. In both groups, mental component summary scores were higher than physical component summary scores. CONCLUSIONS: Prior participation in the ILI, compared with the DSE group, did not appear to improve subsequent mood or HRQOL during 6 years of postintervention follow-up.