Initial treatment of diabetes in Italy. A nationwide population-based study from of the ARNO Diabetes Observatory.

BACKGROUND AND AIMS: To investigate diabetes treatment initiation and continuation in the next sixth months in newly diagnosed Italian subjects. METHODS AND RESULTS: We analyzed administrative claims of 11,300,750 Italian residents. Subjects with incident diabetes were identified by glucose lowering drug prescriptions, disease-specific co-payment exemptions and hospital discharge codes occurring in 2018 but not in 2017. Incident cases were 65,932 of whom 91.4% received the prescription of a glucose lowering drug. Among the latter, those receiving a prescription of a noninsulin medication but no insulin were 84.8%, those receiving a prescription of insulin only were 9.4%, and those receiving prescriptions of both insulin and noninsulin drugs were 5.8%. Metformin was the most frequently drug initially prescribed in noninsulin treated subjects (~85%) and sulphonylurea receptor (SUR) agonists collectively ranked as second (~13%). Lispro (35%) and glargine (34%) were the most frequently prescribed molecules in subjects who were insulin treated. Differences in prescriptions were found in age categories, with increased use of SUR agonists across decades. In the first six months, as many as 50% of noninsulin treated patients continued with the initial drug, ~15% added a second agent, ~5% switched to another medication, and ~30% discontinued any glucose lowering treatment. CONCLUSIONS: These data document that current guidelines are often neglected because prescriptions of SUR agonists as first agent are still quite common and insulin is prescribed more than expected. They point out the urgent need to improve the dissemination and implementations of guidelines in diabetes care.

Patient Engagement With an Automated Telephone Symptom Management Intervention: Predictors and Outcomes.

BACKGROUND: Self-management of symptoms related to cancer and its treatment is important for maintaining treatment regimens and improving outcomes. PURPOSE: To determine factors associated with engagement in a symptom self-management intervention among patients initiating oral anticancer treatment. METHODS: This secondary analysis included 127 patients randomized to the medication adherence reminder and symptom management intervention in a recently completed trial. Patients were recruited from six Comprehensive Cancer Centers, interviewed at intake, and mailed a Symptom Management Toolkit (Toolkit) with self-care management strategies for 18 symptoms. During eight automated telephone weekly calls, patients were asked to use the Toolkit to manage elevated symptoms. Toolkit use and symptoms were tracked weekly, and generalized linear mixed-effects models were used to determine factors predictive of Toolkit use. General linear modeling was used to relate the Toolkit use during intervention to postintervention symptom severity. RESULTS: Better cognitive function at intake into the trial and higher symptom burden were predictive of the patients' initial decision to try the Toolkit during Week 1. In subsequent weeks, Toolkit use in the previous week and worsening of symptoms were associated with greater odds of Toolkit use. The extent of Toolkit use modified the relationship between intake and 8 week symptom severity: among patients with higher levels of severity at intake, use of the Toolkit conferred greater benefit at 8 weeks. CONCLUSIONS: Patients make realistic decisions regarding when to use a self-directed approach to self-management and are likely to use strategies when their symptoms are higher and to forego use once symptoms subside. CLINICAL TRIAL REGISTRATION: NCT02043184.

Effects of depressive symptomatology on cancer-related symptoms during oral oncolytic treatment.

OBJECTIVE: This manuscript assesses association between depressive symptoms and symptoms from cancer and its treatment during the first 12 weeks of a new oral oncolytic treatment. METHODS: This secondary analysis used data from a recently completed trial of an intervention to improve adherence to oral oncolytic treatment and manage symptoms. Following the initiation of the new oral oncolytic medication, 272 patients were interviewed at intake and weeks 4, 8, and 12 to assess depressive symptoms, and symptoms from cancer and its treatment. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D20). The summed index of 18 cancer-related and treatment-related symptoms as well as the number of symptoms above threshold at intake, weeks 4, 8, and 12 were related to intake and time-varying CES-D20 using linear mixed effects models. RESULTS: Depressive symptomatology was a significant predictor of cancer-related and treatment-related symptoms at all-time points, but the strength of this relationship was greatest at the time of oral oncolytic agent initiation and at week 4. The strength of this relationship was the same for both summed symptom severity index and the number of symptoms above threshold, and using either intake or time-varying CES-D20. CONCLUSION: Introducing strategies to treat and manage symptoms of depression along with other symptoms might have added benefits among patients who start a new oral oncolytic treatment and report modest to higher levels of depressive symptoms. Assessments for the impact of strategies to lower depressive symptoms can be taken within the first 4 weeks.

Oral Agents for the Treatment of Gestational Diabetes.

PURPOSE OF REVIEW: To review the current evidence of the safety and efficacy of the use of oral agents for treatment of gestational diabetes (GDM). RECENT FINDINGS: The use of metformin and glyburide in pregnancy for treatment of GDM has dramatically increased since the early 2000s. Meta-analyses suggest that glyburide may increase the risk for large for gestational (LGA) infants and neonatal hypoglycemia. Conversely, metformin may potentially decrease rates of pregnancy-induced hypertension, LGA, neonatal hypoglycemia, and maternal weight gain. However, recent long-term offspring studies indicate a potential detrimental effect of metformin on fat mass that suggests an effect of such medication on fetal programming. While there have been several novel oral anti-diabetes medications brought to market in the past decade, there is minimal data to guide use and in particular data regarding long-term safety for the exposed offspring of treated women. Most professional societies recommend insulin as first-line treatment of gestational diabetes after failure of lifestyle modification. Both metformin and glyburide cross the placenta and long-term safety data is limited. However, patient satisfaction is substantially higher with use of oral agents, and the current literatures suggest that metformin may reduce several common short-term adverse outcomes related to GDM.

Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review.

BACKGROUND: Pregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been most commonly studied, but oral agents would be ideal for use in busy and resource-constrained settings. OBJECTIVES: To review systematically, the effectiveness of oral antihypertensive agents for treatment of severe pregnancy/postpartum hypertension. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE and the Cochrane Library was performed. SELECTION CRITERIA: Randomised controlled trials in pregnancy and postpartum with at least one arm consisting of a single oral antihypertensive agent to treat systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 110 mmHg. DATA COLLECTION AND ANALYSIS: Cochrane RevMan 5.1 was used to calculate relative risk (RR) and weighted mean difference by random effects. MAIN RESULTS: We identified 15 randomised controlled trials (915 women) in pregnancy and one postpartum trial. Most trials in pregnancy compared oral/sublingual nifedipine capsules (8-10 mg) with another agent, usually parenteral hydralazine or labetalol. Nifedipine achieved treatment success in most women, similar to hydralazine (84% with nifedipine; relative risk [RR] 1.07, 95% confidence interval [95% CI] 0.98-1.17) or labetalol (100% with nifedipine; RR 1.02, 95% CI 0.95-1.09). Less than 2% of women treated with nifedipine experienced hypotension. There were no differences in adverse maternal or fetal outcomes. Target BP was achieved ~ 50% of the time with oral labetalol (100 mg) or methyldopa (250 mg) (47% labetelol versus 56% methyldopa; RR 0.85 95% CI 0.54-1.33). CONCLUSIONS: Oral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy/postpartum.

Patient Reported Outcomes and Unscheduled Health Services use During Oral Anti-Cancer Treatment.

CONTEXT: People on oral anti-cancer agents must self-manage their symptoms with less interaction with oncology providers compared to infusion treatments. Symptoms and physical function are key patient-reported outcomes (PROs) and may lead to unscheduled health services uses (urgent care and emergency department [ED] visits, hospitalizations), which in turn lead to increased health care costs. OBJECTIVES: To evaluate the prediction of unscheduled health services uses using age, sex, and comorbidity, then determine the extent to which PRO data (symptoms and functioning) improve that prediction. METHODS: This post-hoc exploratory analysis was based on data from the control group of a trial of medication adherence reminder and symptom self-management intervention for people starting a new oral anti-cancer agent (n = 117 analyzed). Severity and interference with daily life for 18 symptoms, physical function, and depressive symptoms were assessed at intake (oral agent start), and four, eight, and 12 weeks later. Unscheduled health services use during three four-week periods after the start of oral agents was analyzed using generalized mixed effects models in relation to age, sex, comorbidity, and PROs at the beginning of each time period. RESULTS: The summed severity index of 18 symptoms and physical function were significant predictors of hospitalizations in the four weeks following PRO assessment. The addition of PROs improved areas under the receiver operating characteristic curves to be over .70 in most time periods. CONCLUSION: Monitoring of PROs has the potential of reducing unscheduled health services use if supportive care interventions are deployed based on their levels.

Efficacy and feasibility of Apatinib and S-1 as a novel oral induction therapy in locally advanced head and neck squamous cell carcinoma: an exploratory phase 2 open-label, single-arm trial.

Objectives: The current standard nonsurgical treatment for locally advanced head and neck squamous cell cancer (LA-HNSCC) is concomitant chemoradiotherapy (CRT). Neoadjuvant chemotherapy combined with CRT has been explored in HNSCC patients and is an acceptable strategy. However, the occurrence of adverse events (AEs) restricts its application. We conducted a clinical study to explore the efficacy and feasibility of a novel induction therapy with orally administered apatinib and S-1 in LA-HNSCC. Materials and methods: This nonrandomized, single-arm, prospective clinical trial included patients with LA-HNSCCs. The eligibility criteria included histologically or cytologically confirmed HNSCC, with at least one radiographically measurable lesion detected by magnetic resonance imaging (MRI) or computerized tomography (CT) scan, age 18-75 years, and a diagnosis of stage III to IVb according to the 7th edition of the American Joint Committee of Cancer (AJCC). Patients received induction therapy with apatinib and S-1 for three cycles (3 weeks/cycle). The primary endpoint of this study was the objective response rate (ORR) to induction therapy. The secondary endpoints included progression-free survival (PFS), overall survival (OS), and AEs during induction treatment. Results: From October 2017 to September 2020, 49 patients with LA-HNSCC were screened consecutively and 38 were enrolled. The median age of the patients was 60 years (range, 39-75). Thirty-three patients (86.8%) had stage IV disease according to the AJCC staging system. The ORR after induction therapy was 97.4% (95% confidence interval [CI]: 86.2%-99.9%). the 3-year OS rate was 64.2% (95% CI: 46.0%-78.2%) and 3-year PFS was 57.1% (95% CI: 40.8%-73.6%). The most common AEs during induction therapy were hypertension and hand-foot syndrome, which were manageable. Conclusion: Apatinib combined with S-1 as novel induction therapy for LA-HNSCC patients resulted in a higher-than-anticipated ORR and manageable adverse effects. With the associated safety profile and preferable oral administration route, apatinib combined with S-1 is an attractive exploratory induction regimen in outpatient settings. However, this regimen failed to show a survival benefit. Clinical trial registration: https://clinicaltrials.gov/show/NCT03267121, identifier NCT03267121.

Immunotherapy Combined with Metronomic Dosing: An Effective Approach for the Treatment of NSCLC.

Pioneering studies on tumor and immune cell interactions have highlighted immune checkpoint inhibitors (ICIs) as revolutionizing interventions for the management of NSCLC, typically combined with traditional MTD chemotherapies, which usually lead to toxicities and resistance to treatment. Alternatively, MTR chemotherapy is based on the daily low dose administration of chemotherapeutics, preventing tumor growth indirectly by targeting the tumor microenvironment. The effects of MTR administration of an oral prodrug of gemcitabine (OralGem), alone or with anti-PD1, were evaluated. Relevant in vitro and in vivo models were developed to investigate the efficacy of MTR alone or with immunotherapy and the potential toxicities associated with each dosing scheme. MTR OralGem restricted tumor angiogenesis by regulating thrombospondin-1 (TSP-1) and vascular endothelial growth factor A (VEGFA) expression. MTR OralGem enhanced antitumor immunity by increasing T effector responses and cytokine release, concomitant with dampening regulatory T cell populations. Promising pharmacokinetic properties afforded minimized blood and thymus toxicity and favorable bioavailability upon MTR administration compared to MTD. The combination of MTR OralGem with immunotherapy was shown to be highly efficacious and tolerable, illuminating it as a strong candidate therapeutic scheme for the treatment of NSCLC.

Relationship between Health Literacy and Medication Adherence of Turkish Cancer Patients Receiving Oral Chemotherapy.

OBJECTIVE: The aim of this study was to explore the relationship between health literacy and self-report medication adherence of Turkish cancer patients receiving oral chemotherapy. METHODS: The present research was a descriptive and cross-sectional study and conducted with 100 voluntary cancer patients who were admitted to the medical oncology outpatient clinic and received oral chemotherapy. The data were collected through a questionnaire form consisting of the Oral Chemotherapy Adherence Scale and the Turkish Health Literacy Scale (TSOY-32). The collected data were analyzed using descriptive statistics, one-way ANOVA, and Pearson's correlation coefficient. RESULTS: The results revealed that 57% of the patients were female, 35% were primary school graduates, 51% were breast cancer, and 36% took capecitabine. The mean index scores of the participants on both scales were calculated as 12.39 ± 1.51 and 73.25 ± 6.18, respectively. Overall, a positive and strong correlation was found between oral chemotherapy adherence and health literacy of the participants (r = 0.707, P = 0.000). CONCLUSIONS: Medication adherence and health literacy levels among the cancer patients in Turkey are alarming so that patient-centered interventions and training are required to overcome the barriers to medication adherence.

An Automated Intervention Did Not Improve Adherence to Oral Oncolytic Agents While Managing Symptoms: Results From a Two-Arm Randomized Controlled Trial.

CONTEXT: An increasing number of oral cancer treatments require patient adherence and symptom self-management. OBJECTIVES: The report presents the effects of a medication reminder and symptom management intervention directed at patients initiating new oral oncolytic agents. METHODS: Patients (N = 272) were recruited at six comprehensive cancer centers, interviewed over the telephone after oral agent initiation, and randomized to either standard care or a medication reminder and symptom management intervention. In the intervention arm, the automated system called patients daily to remind them about taking their medications and weekly to assess 18 symptoms and refer patients to a printed Medication Management and Symptom Management Toolkit. Severity of 18 symptoms was also assessed during telephone interviews at Week 4 (midintervention), Week 8 (postintervention), and Week 12 (follow-up). Adherence was measured using the relative dose intensity, the ratio of dose taken by patient out of dose prescribed by the oncologist, and assessed using pill counts at Weeks 4, 8, and 12 and prescribing information from medical records. RESULTS: The relative dose intensity was high and did not differ by trial arm. Symptom severity was significantly lower (P < 0.01) in the experimental arm at Week 8 but not at Weeks 4 or 12. CONCLUSION: Adherence may be less of a problem than originally anticipated, and intervention was not efficacious possibly because of already high rates of patient adherence to oral oncolytic medication during first 12 weeks. Longer follow-up in future research may identify subgroups of patients who need interventions to sustain adherence.

Oral Agents: Challenges With Self-Administered Medication Adherence in Clinical Trials.

BACKGROUND: In oral agent clinical trials, patients may not be adherent to self-administration of study medication; this nonadherence can affect validity and reliability. Many factors contribute to nonadherence to protocol requirements, and managing patients with fidelity issues is the responsibility of the research team. OBJECTIVES: The aim is to identify which group (patients, physicians/principal investigators, nurses, or other personnel) research nurses report as most responsible for protocol nonadherence and to characterize the most observed causes and contributors to nonadherence within each group. METHODS: Sixty-seven protocol nurses completed a nine-question survey developed from pilot data. Descriptive statistics and ordinal regressions addressed the objectives of the study. FINDINGS: More than half of the nurses observed clinical trial nonadherence in their practices. Nurses identified challenges regarding physician, patient, and nurse factors. The most frequently identified causes included patients' forgetfulness, refusal to undergo study procedures, inadequate family or caregiver support to complete study activities, ineffective communication, and collaboration within the research team.

Comparison of efficacy and safety of oral agents for the treatment of relapsing-remitting multiple sclerosis.

In the therapeutic scenario of disease-modifying therapies for relapsing-remitting multiple sclerosis, the introduction of oral agents, starting in 2010 with fingolimod, has been a huge step forward in therapeutic options due to the easier administration route. Three oral drugs fingolimod, teriflunomide, and dimethyl fumarate, which are clinically approved for the treatment of relapsing-remitting multiple sclerosis, are reviewed in this work. Results of Phase III clinical trials and their extension studies showed that the three oral agents significantly reduced the annualized relapse rate - a superior efficacy compared to placebo. Fingolimod 0.5 mg consistently reduced clinical relapses and brain volume loss. In all Phase III studies, teriflunomide 14 mg dose showed a reduction in the risk of disability accumulation. Regarding safety profile, fingolimod had more safety issues than the other two agents. For this reason, it should be strictly monitored for risks of infections, cancers, and certain transitory effects such as irregular cardiac function, decreased lymphocyte count, and a higher level of liver enzymes. Adverse effects of teriflunomide are well characterized and can be considered manageable. The main risks marked with dimethyl fumarate were flushing and gastrointestinal events.

The Effect of Structured Education to Patients Receiving Oral Agents for Cancer Treatment on Medication Adherence and Self-efficacy.

OBJECTIVE: This study was conducted to examine the effect of structured education on medication adherence and self-efficacy through the use of the MASCC Oral Agent Teaching Tool (MOATT) for patients receiving oral agents for cancer treatment. METHODS: This quasi-experimental study has been conducted at two hospitals; 41 patients were included in the study. Data were obtained using a questionnaire, medication adherence self-efficacy scale (MASES), memorial symptom assessment scale, and a follow-up form (diary). Patients were educated through the use of the MOATT at a scheduled time; drug-specific information was provided along with a treatment scheme and follow-up diary. Phone interviews were completed 1 and 2 weeks after the educational session. At the next treatment cycle, the patients completed the same questionnaires. RESULTS: Majority of the patients were receiving capecitabine (90.2%; n = 37) as an oral agent for breast (51.2%; n = 21) and stomach cancer (24.6%; n = 10) treatment. About 90.2% of patients (n = 37) stated that they did not forget to take their medication and experienced medication-related side effects (78%; n = 32). The total score of MASES was increased after the education (66.39 vs. 71.04, P < 0.05). CONCLUSIONS: It was shown that individual education with the MOATT and follow-up for patients receiving oral agents for cancer treatment increased patient medication adherence self-efficacy.

Clinical backgrounds associated with discrepancy between subjective and objective assessments of medication adherence in Japanese type 2 diabetic patients.

Although medication adherence can be easily assessed by self-reports in clinical practice, accuracy is sometimes questionable. To make full use of self-reports on medication adherence in clinical practice, understanding the discrepancy between subjectively and objectively assessed adherence is important. The aim of this study was to investigate which clinical characteristics would be associated with such discrepancy regarding adherence to oral antidiabetic drugs (OADs) in type 2 diabetic patients. Our study assessed 406 Japanese type 2 diabetic outpatients treated with OADs. Medication adherence to OADs was evaluated in percentage, both subjectively by self-report and objectively by pill counts on the same day. We developed a common regression model by extending the generalized linear mixed model and statistically detected the difference in the impact of clinical characteristics between the two measures. Subjectively measured adherence was higher than objectively measured adherence, showing a 1.6-fold difference in odds (p < 0.001). Male gender, older age, longer diabetic duration, and taking more than two OADs daily were independently associated with the overrating of medication adherence by self-report compared with the objectively measured adherence. On the other hand, higher glycocylated hemoglobin (HbA1c) levels, taking medication before meals, and taking medication outside the home were independently associated with underrating medication adherence by self-report. In conclusion, this study demonstrated clinical characteristics associated with overrating and underrating of medication adherence by self-report in Japanese type 2 diabetic patients treated with OADs.

Empagliflozin in combination with oral agents in young and overweight/obese Type 2 diabetes mellitus patients: A pooled analysis of three randomized trials.

AIMS: This analysis aimed to evaluate efficacy and safety of empagliflozin in combination therapy in <65 y.o. patients, overweight/obese, and with uncontrolled T2DM. METHODS: Pooled analysis from three phase-III trials, in <65 y.o. patients, with BMI 25-35kg/m2, and HbA1c ≥8% at baseline. Patients (N=439) were randomized to placebo (n=138), empagliflozin 10mg (n=160), or empagliflozin 25mg (n=141) once daily (24weeks) as add-on to metformin, to metformin plus sulfonylurea, or to pioglitazone ± metformin. RESULTS: At week 24, adjusted mean (SE) changes from baseline in HbA1c were -0.19% (0.07) for placebo vs. -1.10% (0.07) and -1.10% (0.07) for empagliflozin 10 and 25mg, respectively (both p<0.001). Adjusted mean (SE) changes from baseline in weight were -0.33kg (0.21) for placebo vs. -1.94kg (0.19) and -2.14kg (0.20) for empagliflozin 10 and 25mg, respectively (both p<0.001). Adverse events were reported in 57.2% on placebo, 64.4% on empagliflozin 10mg and 59.6% on empagliflozin 25mg. Genital infection AEs were reported in 1.4% on placebo, 3.8% on empagliflozin 10mg, and 5.0% on empagliflozin 25mg. CONCLUSIONS: In this specific population, empagliflozin in combination with other oral agents, significantly reduced HbA1c and body weight and was well tolerated.

Overview of the challenges related to oral agents for cancer and their impact on adherence.

BACKGROUND: The increasing number and complexity of oral agents for cancer (OACs) have created a paradigm shift in the process and outcomes in oncology care. With 25%-30% of new oncology medications in development being oral agents, and a steady increase in approvals in the past 5-10 years, the issues are relevant in clinical practice. OBJECTIVES: The purpose of this article is to provide an overview of the challenges related to OACs, including adherence, and to describe the consequences of adherence and resources for oncology nurses. METHODS: The literature was searched to determine challenges related to OACs and their impact on adherence, and an overview of the issues was compiled. FINDINGS: Oncology nurses are key stakeholders in recognizing the challenges and issues associated with the change in treatment regarding OACs. Oncology nurses are an integral part of managing the oral agent process, from access to adherence. Oncology nurses need to understand the issues surrounding OACs so that adherence practices can be improved.

Why patients prescribed oral agents for cancer need training: a case study.

BACKGROUND: Oral agents for cancer (OACs) are a common form of treatment. However, with OACs, the responsibility shifts from supervised healthcare providers who work in a clinic to patients and caregivers who must manage treatment on their own at home. Consequently, patients and caregivers must be knowledgeable about all aspects of care. In addition, most patients with cancer are older and have multiple comorbid conditions treated by several providers who prescribe medications, further complicating care. OBJECTIVES: This purpose of this article is to present a patient perspective of managing treatment with OACs in the home setting. METHODS: A case study format was used to describe challenges faced by a patient newly prescribed OACs. FINDINGS: Data from the patient interviews support the urgent need for patient and caregiver training; the outcome of treatment for patients taking OACs depends significantly on the patient or caregiver managing treatment in the home setting.

Assessment and measurement of medication adherence: oral agents for cancer.

BACKGROUND: Clinicians are challenged to find ways to assess and measure adherence to oral agents for cancer (OACs). OBJECTIVES: The purpose of this article is to report on available ways to assess and measure medication adherence by patients with cancer. METHODS: Tools examined include the Morisky Medication Adherence Scale (MMAS) and the Adherence Estimator, which are able to predict risk of nonadherence. Adherence Starts With Knowledge (ASK®)-12 and the Brief Adherence Rating Scale (BARS) are likely to be effective for predicting nonadherence and measuring adherence rates. FINDINGS: Additional research needs to focus on the testing of reliable and valid tools that are sensitive and specific to patients with cancer who are prescribed OACs. The authors found that the MMAS and Adherence Estimator tools may be useful at predicting risk of medication nonadherence, and the ASK-12 and BARS may be useful for measuring rates of adherence. Tools could be modified to a specific clinical setting and used in a standardized format so that nurses can assess risk of medication nonadherence and measure adherence rates of OACs.

Gestational diabetes mellitus: challenges in diagnosis and management.

Gestational diabetes mellitus (GDM) is a well-characterized disease affecting a significant population of pregnant women worldwide. It has been widely linked to undue weight gain associated with factors such as diet, obesity, family history, and ethnicity. Poorly controlled GDM results in maternal and fetal morbidity and mortality. Improved outcomes therefore rely on early diagnosis and tight glycaemic control. While straightforward protocols exist for screening and management of diabetes mellitus in the general population, management of GDM remains controversial with conflicting guidelines and treatment protocols. This review highlights the diagnostic and management options for GDM in light of recent advances in care.

Severe hypoglycemia is associated with antidiabetic oral treatment compared with insulin analogs in nursing home patients with type 2 diabetes and dementia: results from the DIMORA study.

OBJECTIVES: Severe hypoglycemia is associated with cognitive decline and dementia in older persons with type 2 diabetes. The role of antidiabetic treatments on severe hypoglycemia is unknown in dementia. The aims were to determine the prevalence of severe hypoglycemic events and investigate associations among severe hypoglycemic and specific antidiabetic treatments (classes of oral agents and types of insulin analogs) in a large sample of nursing home patients with diabetes according to dementia status. DESIGN: Cross-sectional observational study. SETTING: A total of 150 nursing homes across Italy. PARTICIPANTS: A total of 2258 patients with type 2 diabetes (dementia = 1138, no dementia = 1120). MEASUREMENTS: Diagnosis of dementia before nursing home admission. Data were collected regarding functional status, glycemic control, antidiabetic treatments, comorbidities, and biochemical and clinical measurements. Logistic regression models with severe hypoglycemia as the dependent variable were used to test associations with antidiabetic agents. RESULTS: Patients had a mean age (SD) of 82 (8) years, body mass index (BMI) of 25.4 (4.8), fasting plasma glucose (FPG) of 7.5 (3.0) mmol/L, postprandial glucose (PPG) of 10.3 (3.6) mmol/L, HbA1c of 7.1% (54 mmol/L), and impairments in activities of daily living (ADLs) of 3.7 (2.1). Severe hypoglycemia was more prevalent in patients with dementia (18%) compared with patients without dementia (8%). Patients with dementia were older, showed greater ADL impairments, greater number of comorbidities, lower FPG, and higher PPG compared with those without dementia. Adjusted logistic regression models in patients with dementia showed that rapid- and long-acting insulin analogs were associated with reduced odds ratio (OR) (OR 0.333; 95% confidence interval [CI] 0.184-0.602; OR 0.248, 95% CI 0.070-0.882, respectively), whereas sulphonylureas and combined metformin + sulphonylurea were associated with increased ORs (OR 8.805, 95% CI 4.260-18.201; OR 6.639; 95% CI 3.273-14.710, respectively) of experiencing severe hypoglycemia. No correlations were found in patients without dementia. CONCLUSION: In older nursing home patients with type 2 diabetes, severe hypoglycemia was significantly higher in dementia. Our findings suggest that sulphonylureas should be used with caution, whereas rapid- and long-acting insulin analogs seem safer.