Addressing Therapeutic Inertia: Development and Implementation of an Electronic Health Record-Based Diabetes Intensification Tool.

Objective: To assess whether an electronic health record (EHR)-based diabetes intensification tool can improve the rate of A1C goal attainment among patients with type 2 diabetes and an A1C ≥8%. Methods: An EHR-based tool was developed and sequentially implemented in a large, integrated health system using a four-phase, stepped-wedge design (single pilot site [phase 1] and then three practice site clusters [phases 2-4]; 3 months/phase), with full implementation during phase 4. A1C outcomes, tool usage, and treatment intensification metrics were compared retrospectively at implementation (IMP) sites versus nonimplementation (non-IMP) sites with sites matched on patient population characteristics using overlap propensity score weighting. Results: Overall, tool utilization was low among patient encounters at IMP sites (1,122 of 11,549 [9.7%]). During phases 1-3, the proportions of patients achieving the A1C goal (<8%) were not significantly improved between IMP and non-IMP sites at 6 months (range 42.9-46.5%) or 12 months (range 46.5-53.1%). In phase 3, fewer patients at IMP sites versus non-IMP sites achieved the goal at 12 months (46.7 vs. 52.3%, P = 0.02). In phases 1-3, mean changes in A1C from baseline to 6 and 12 months (range -0.88 to -1.08%) were not significantly different between IMP and non-IMP sites. Times to intensification were similar between IMP and non-IMP sites. Conclusion: Utilization of a diabetes intensification tool was low and did not influence rates of A1C goal attainment or time to treatment intensification. The low level of tool adoption is itself an important finding highlighting the problem of therapeutic inertia in clinical practice. Testing additional strategies to better incorporate, increase acceptance of, and improve proficiency with EHR-based intensification tools is warranted.

Erratum: Addressing Therapeutic Inertia: Development and Implementation of an Electronic Health Record-Based Diabetes Intensification Tool. Diabetes Spectrum 2023;36:161-170 (https://doi.org/10.2337/ds22-0031).

[This corrects the article DOI: 10.2337/ds22-0031.].

Medication use by US patients with pulmonary hypertension associated with chronic obstructive pulmonary disease: a retrospective study of administrative data.

BACKGROUND: Pulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD). While clinical guidelines recommend specific drug therapies for pulmonary arterial hypertension (PAH), these drug therapies are not recommended for PH due to lung disease. METHODS: This was a retrospective cohort study using the Optum® Clinformatics® Data Mart from January 2009-September 2019. An algorithm was designed to identify adults with ≥ 2 ICD-9-CM or ICD-10-CM diagnosis codes for PH and with ≥ 2 diagnosis codes for COPD. Sensitivity analyses were conducted among subgroups of patients with evidence of a right heart catheterization (RHC) or pulmonary function test (PFT). Patient characteristics, medications used, and durations of use of PAH and COPD medications were analyzed. RESULTS: A total of 25,975 patients met the study inclusion criteria. Their mean age was 73.5 (SD 10.0) years and 63.8% were female. Medications targeting PAH were prescribed to 643 (2.5%) patients, most frequently a phosphodiesterase-5 inhibitor (2.1%) or an endothelin receptor antagonist (0.75%). Medications for COPD were prescribed to 17,765 (68.4%) patients, most frequently an inhaled corticosteroid (57.4%) or short-acting beta agonist (50.4%). The median durations of use ranged from 4.9 to 12.8 months for PAH medications, and from 0.4 to 5.9 months for COPD medications. Of the subgroup of patients with RHC (N = 2325), 257 (11.1%) were prescribed a PAH medication and 1670 (71.8%) used a COPD medication. Of the subgroup with a PFT (N = 2995), 58 (1.9%) were prescribed a PAH medication and 2100 (70.1%) a COPD medication. CONCLUSIONS: Patients with PH associated with COPD were identified in a US administrative claims database. Very few of these patients received any of the medications recommended for PAH, and only about two thirds received medications for COPD.

Factors associated with switching from sulphonylureas to dipeptidyl peptidase 4 inhibitors among patients with type 2 diabetes in the United States.

AIMS: Studies examining the prevalence of and factors associated with switching from sulphonylureas (SUs) to dipeptidyl peptidase 4 (DPP-4) inhibitors in real-world settings are lacking. We assessed the factors associated with switching from SUs to DPP-4 inhibitors in the United States. MATERIALS AND METHODS: This retrospective cohort study was conducted using the Optum Clinformatics® Data Mart (2009-2018). Adults with type 2 diabetes and newly prescribed at least two SUs were included and were followed for 2 years after the initiation of SU (index date). We compared the characteristics of those who switched from SUs to DPP-4 inhibitors (only; no additional antidiabetic drugs) with those who continued with SUs (without adding other antidiabetic drugs) using multivariate logistic regression. Multinomial regression analyses were also conducted to assess the factors associated with switching to different drug classes versus continuation with SUs. RESULTS: In a sample of 119 107 new SU users, 2.2% (2633) switched to DPP-4 inhibitors, 3.8% (4542) switched to antidiabetic drugs other than DPP-4 inhibitors, 68.3% (81 394) discontinued SUs but did not switch to another antidiabetic drug, 12.9% (15 345) continued with SUs and added other antidiabetic drugs, and 12.8% (15 193) continued with SUs only. Multivariate logistic regression showed that those who had significantly higher likelihood of switching were younger, female [vs. males; adjusted odds ratio (AOR) = 0.70], and living in the south; had previous use of DPP-4 inhibitors (AOR = 1.71); were not using antidiabetic drugs at baseline; had more baseline diabetes-related emergency room visits (AOR = 1.13), depression (AOR = 1.34), post-index hypoglycaemia (AOR = 2.20), and an earlier index year; and were glyburide users (vs. glimepiride users; AOR = 1.29). CONCLUSIONS: The discontinuation rate for SUs is high. Factors associated with switching from SUs to DPP-4 inhibitors included age, sex, geographic region, baseline antidiabetic drug use, type of SU, baseline diabetes-related emergency room visits, hypoglycaemia and depression.

Strategies for overcoming therapeutic inertia in type 2 diabetes: A systematic review and meta-analysis.

AIMS: To systematically investigate the effect of interventions to overcome therapeutic inertia on glycaemic control in individuals with type 2 diabetes. MATERIALS AND METHODS: We electronically searched for randomized controlled trials or quasi-experimental studies published between January 1, 2004 and December 31, 2019 evaluating the effect of interventions on glycated haemoglobin (HbA1c) control. Characteristics of included studies and HbA1c difference between intervention and control arms (main outcome) were extracted. Interventions were grouped as: care management and patient education; nurse or certified diabetes educator (CDE); pharmacist; or physician-based. RESULTS: Thirty-six studies including 22 243 individuals were combined in nonlinear random-effects meta-regressions; the median (range) duration of intervention was 1 year (0.9 to 36 months). Compared to the control arm, HbA1c reduction ranged from: -17.7 mmol/mol (-1.62%) to -4.4 mmol/mol (-0.40%) for nurse- or CDE-based interventions; -13.1 mmol/mol (-1.20%) to 3.3 mmol/mol (0.30%) for care management and patient education interventions; -9.8 mmol/mol (-0.90%) to -6.6 mmol/mol (-0.60%) for pharmacist-based interventions; and -4.4 mmol/mol (-0.40%) to 2.8 mmol/mol (0.26%) for physician-based interventions. Across the included studies, a reduction in HbA1c was observed only during the first year (6 months: -4.2 mmol/mol, 95% confidence interval [CI] -6.2, -2.2 [-0.38%, 95% CI -0.56, -0.20]; 1 year: -1.6 mmol/mol, 95% CI -3.3, 0.1 [-0.15%, 95% CI -0.30, 0.01]) and in individuals with preintervention HbA1c >75 mmol/mol (9%). CONCLUSIONS: The most effective approaches to mitigating therapeutic inertia and improving HbA1c were those that empower nonphysician providers such as pharmacists, nurses and diabetes educators to initiate and intensify treatment independently, supported by appropriate guidelines.

Addressing Therapeutic Inertia in 2020 and Beyond: A 3-Year Initiative of the American Diabetes Association.

Research has shown that getting to glycemic targets early on leads to better outcomes in people with type 2 diabetes; yet, there has been no improvement in the attainment of A1C targets in the past decade. One reason is therapeutic inertia: the lack of timely adjustment to the treatment regimen when a person's therapeutic targets are not met. This article describes the scope and priorities of the American Diabetes Association's 3-year Overcoming Therapeutic Inertia Initiative. Its planned activities include publishing a systematic review and meta-analysis of approaches to reducing therapeutic inertia, developing a registry of effective strategies, launching clinician awareness and education campaigns, leveraging electronic health record and clinical decision-support tools, influencing payer policies, and potentially executing pragmatic research to test promising interventions.

Cost-effectiveness of intensification with sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes on metformin and sitagliptin vs direct intensification with insulin in the United Kingdom.

AIM: To evaluate the long-term cost-effectiveness of an intensification strategy with sodium-glucose co-transporter-2 (SGLT2) inhibitors (pathway 1) compared with NPH insulin (pathway 2) in patients with type 2 diabetes (T2D) in the United Kingdom who were not at goal on metformin and sitagliptin. METHODS: Cost-effectiveness analysis was performed using the well-established, validated IQVIA CORE Diabetes Model from the payer perspective over a patient's lifetime. Randomized clinical trials informed treatment effect measures, while public or published sources informed economic inputs. Scenario analyses of glycated haemoglobin (HbA1c), hypoglycaemia rate, body mass index effects, SGLT2 inhibitor cardiovascular protective effects, and population characteristics were conducted to assess the robustness of results. RESULTS: Pathway 1 increased life-years and quality-adjusted life-years (QALYs) compared with pathway 2 (13.49 vs. 13.37, and 9.40 vs. 9.22, respectively). Additional drug costs in pathway 1 were offset by diabetes-related complication decreases, leading to slightly lower direct medical costs for pathway 1 (£25747 vs £26095). Pathway 1 was therefore cost-neutral (no interpretable incremental cost-effectiveness ratio), while improving clinical outcomes. Scenario analyses consistently showed cost-neutrality or cost-effectiveness of pathway 1. The highest result remained less than £3000/QALY, reflecting older patients (≥65 years) with lower baseline HbA1c (7%). CONCLUSIONS: For UK patients with T2D not at goal on metformin and sitagliptin therapy, treatment intensification with SGLT2 inhibitors prior to NPH insulin is cost-neutral or cost-effective compared with immediate NPH insulin intensification.

Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival.

AIMS: To characterize survival in relation to achieved glycated haemoglobin (HbA1c) level within alternative glucose-lowering regimens with differing risks of hypoglycaemia. METHODS: Data were extracted from the UK Clinical Practice Research Datalink and the corresponding Hospital Episode Statistics. Patients with type 2 diabetes prescribed glucose-lowering therapy in monotherapy or dual therapy with metformin between 2004 and 2013 were identified. Risk of all-cause mortality within treatment cohorts was evaluated using the Cox proportional hazards model, introducing mean HbA1c as a quarterly updated, time-dependent covariable. RESULTS: There were 6646 deaths in a total follow-up period of 374 591 years. Survival for lower (<7%) vs moderate HbA1c levels (≥7%, <8.5%) differed by cohort: metformin, adjusted hazard ratio (aHR) 1.03 (95% confidence interval [CI] 0.95-1.12); sulphonylurea, aHR 1.11 (95% CI 0.99-1.25); insulin, aHR 1.47 (95% CI 1.25-1.72); combined regimens with low hypoglycaemia risk, aHR 1.02 (95% CI 0.94-1.10); and combined regimens with higher hypoglycaemia risk excluding insulin, aHR 1.24 (95% CI 1.13-1.35) and including insulin, aHR 1.28 (95% CI 1.18-1.37). Higher HbA1c levels were associated with increased mortality in regimens with low hypoglycaemia risk. Post hoc analysis by HbA1c deciles revealed an elevated risk of all-cause mortality for the lowest deciles across all cohorts, but particularly in those regimens associated with hypoglycaemia. High HbA1c was associated with no difference, or a small increase in mortality risk in regimens with increased risk of hypoglycaemia. CONCLUSIONS: The pattern of mortality risk across the range of HbA1c differed by glucose-lowering regimen. Lower HbA1c was associated with increased mortality risk compared with moderate control, especially in those regimens associated with hypoglycaemia. High levels of HbA1c were associated with the expected elevated mortality risk in regimens with low hypoglycaemia risk.

Two Randomized Controlled Pilot Trials of Social Forces to Improve Statin Adherence among Patients with Diabetes.

BACKGROUND: Medication nonadherence is an important obstacle to cardiovascular disease management. OBJECTIVE: To improve adherence through real-time feedback based on theories of how social forces influence behavior. DESIGN: Two randomized controlled pilot trials called PROMOTE and SUPPORT. Participants stored statin medication in wireless-enabled pill bottles that transmitted adherence data to researchers. PARTICIPANTS: Adults with diabetes and a history of low statin adherence based on pharmacy refills (i.e., Medication Possession Ratio [MPR] <80% in the pre-randomization screening period). INTERVENTION: In PROMOTE, each participant was randomized to 1) weekly messages in which that participant's statin adherence was compared to that of other participants (comparison), 2) weekly summaries of that participant's statin adherence (summary), or 3) control. In SUPPORT, each participant identified another person (the Medication Adherence Partner [MAP]) to receive reports about that participant's adherence, and was randomized to 1) daily reports to MAP, 2) weekly reports to MAP, 3) reports to MAP only if dose was missed, or 4) control. MAIN OUTCOMES MEASURE: Adherence measured by pill bottle. KEY RESULTS: Among 45,000 health plan members contacted by mail, <1% joined the trial. Participants had low baseline MPRs (median = 60%, IQR 41-72%) but high pill-bottle adherence (90% in PROMOTE, 92% in SUPPORT) during the trial. In PROMOTE (n = 201) and SUPPORT (n = 200), no intervention demonstrated significantly better adherence vs. CONTROL: In a subgroup of PROMOTE participants with the lowest pre-study MPR, pill-bottle-measured adherence in the comparison arm (89%) was higher than the control (86%) and summary (76%) arms, but differences were non-significant (p = 0.10). CONCLUSIONS: Interventions based on social forces did not improve medication adherence vs. control over a 3-month period. Given the low percentage of invited individuals who enrolled, the studies may have attracted participants who required little encouragement to improve adherence other than study participation.

Sulfonylurea use and the risk of hospital readmission in patients with type 2 diabetes.

BACKGROUND: Hospital inpatient care for patients with diabetes was estimated to cost $76 billion in 2012. Substantial expense resulted from those patients having multiple hospitalizations. The objective was to compare the risk for diabetes-related hospital readmission in patients with type 2 diabetes treated with sulfonylureas (SUs) compared to those treated with other oral antihyperglycemic agents (AHAs). METHODS: A retrospective cohort analysis was conducted using two-year panels, from 1999 to 2010, from the Medical Expenditure Panel Survey. The study included patients with type 2 diabetes taking an oral AHA who experienced a diabetes-related hospitalization. A Cox proportional hazard regression predicting time to readmission was used to estimate and compare the risks of readmission for SU-monotherapy versus other-AHA-monotherapy patients. Covariates included age, gender, marital status, cardiovascular disease, kidney disease, and eye disease, along with a propensity score to control for selection bias. The lack of clinical data on disease severity and progression limited our ability to estimate causal relationships between drug use and risk of hospital readmission. RESULTS: From 1999 to 2010, an estimated 13.5 million patients experienced a diabetes-related hospital admission and subsequent AHA treatment. While 23.2 % (n = 746,579) of patients in the SU monotherapy cohort had a readmission, only 16.1 % (n = 881,984) in the other-AHA monotherapy group were readmitted. Average readmission expenditure for readmitted SU users (in 2010 dollars) was $11,148 (±$1,558) compared to $7,673 (±$763) for users of other oral AHAs. The estimated readmission hazard ratio was 1.29 (95 % CI: 1.01-1.65; p-value = 0.04) for SU monotherapy users. If a patient's first hospital admission was during the time period 2008-2010, a readmission was significantly less likely (HR 0.49, 95 % CI: 0.31-0.78; p = 0.003) relative to 2004-2007. CONCLUSIONS: Among patients with type 2 diabetes, SU use was associated with an approximately 30 % increased risk for readmission compared to other-AHA use, while each readmission for an SU user cost on average 45 % more than one for an other-AHA patient. Because of the rapidly rising prevalence of diabetes in the U.S. and the large number of patients with prediabetes, preventing hospital readmissions will continue to be an important cost-saving strategy in the future.

Prevalence and co-prevalence of comorbidities among Chinese adult patients with type 2 diabetes mellitus: a cross-sectional, multicenter, retrospective, observational study based on 3B study database.

Purpose: This study aimed to investigate the prevalence and co-prevalence of comorbidities among Chinese individuals with type 2 diabetes (T2DM). Methods: Medical records were retrospectively retrieved from the 3B Study database, which provided a comprehensive assessment of comorbid conditions in Chinese adult outpatients with T2DM. Patient characteristics, laboratory measures, and comorbidities were summarized via descriptive analyses, overall and by subgroups of age (<65, 65-74, 75 years) and gender. Results: Among 25,454 eligible patients, 53% were female, and the median age was 63 years. The median time of diabetes duration was 6.18 years. A total of 20,309 (79.8%) patients had at least one comorbid condition alongside T2DM. The prevalence of patients with one, two, three, and four or more comorbid conditions was 28.0%, 24.6%, 15.6%, and 11.6%, respectively. Comorbidity burden increased with longer T2DM duration. Older age groups also exhibited higher comorbidity burden. Females with T2DM had a higher overall percentage of comorbidities compared to males (42.7% vs. 37.1%). The most common comorbid conditions in T2DM patients were hypertension (HTN) in 59.9%, overweight/obesity in 58.3%, hyperlipidemia in 42.0%, retinopathy in 16.5%, neuropathy in 15.2%, cardiovascular disease (CVD) in 14.9%, and renal disease in 14.4%. The highest co-prevalence was observed for overweight/obesity and HTN (37.6%), followed by HTN and hyperlipidemia (29.8%), overweight/obesity and hyperlipidemia (27.3%), HTN and CVD (12.6%), HTN and retinopathy (12.1%), and HTN and renal disease (11.3%). Conclusion: The majority of T2DM patients exhibit multiple comorbidities. Considering the presence of multimorbidity is crucial in clinical decision-making. Systematic review registration: https://clinicaltrials.gov/, identifier NCT01128205.

Impact of dipeptidyl peptidase-4 inhibitors on glucose-dependent insulinotropic polypeptide in type 2 diabetes mellitus: a systematic review and meta-analysis.

Aims: Glucose-dependent insulinotropic polypeptide (GIP) confers a variety of metabolic benefits in type 2 diabetes mellitus (T2DM). This meta-analysis was conducted to investigate the impact of dipeptidyl peptidase 4 (DPP4) inhibitors on GIP levels in T2DM patients. Methods: Medline (PubMed), CENTER (Cochrane Library), and Embase (Ovid) were searched and randomized controlled trials (RCTs) evaluating the impact of DPP4 inhibitors on fasting and postprandial GIP levels were obtained. For postprandial GIP, only studies with the data of GIP changes reported as the total area under the curve (AUCGIP) using a meal or oral glucose tolerance test were included. A random-effects model was used for data pooling after incorporating heterogeneity. Results: Overall, 14 RCTs with 541 T2DM patients were included. Compared to placebo/no treatment, the use of DPP4 inhibitors significantly increased the fasting GIP level (standard mean difference [SMD]: 0.77, 95% confidence interval [CI]: 0.48-1.05, P<0.001; I2 = 52%) and postprandial AUCGIP (SMD: 1.33, 95% CI: 1.02-1.64, P<0.001; I2 = 65%). Influence analysis by excluding one dataset at a time showed consistent results. Sensitivity analyses only including studies with radioimmunoassay showed also consistent results (fasting GIP: SMD: 0.75, 95% CI: 0.51-1.00, P<0.001; I2 = 0%; and postprandial AUCGIP: SMD: 1.48, 95% CI: 1.18-1.78, P<0.001; I2 = 54%). Further subgroup analyses demonstrated that the influence of DPP4 inhibitors on fasting and postprandial GIP levels in T2DM patients was not significantly changed by study characteristics such as study design, patient mean age, baseline glycated hemoglobin (HbA1c) concentration, body mass index (BMI), background treatment, treatment duration, or method for postprandial GIP measurement (all P for subgroup effects <0.05). Conclusion: The use of DPP4 inhibitors effectively increases the fasting and postprandial GIP concentrations in T2DM patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022356716.

Suboptimal adherence to food restrictions requirements related to drug regimens for chronic diseases.

BACKGROUND: Oral medications for chronic conditions often involve a variety of instructions, including time of day/dosing, drug interactions, and food intake restrictions. However, the extent to which patients follow these instructions is unclear. METHODS: We surveyed patients from the US and Europe (UK, France, Germany, Italy, Spain) who were prescribed sulfonylureas (SU: glimepiride, glipizide, or gliclazide) for diabetes or levothyroxine for hypothyroidism. Patients kept a daily diary for 3-5 days documenting their adherence to three criteria: dosing regimen including time of day, warning labels including drug interactions, and food restrictions. RESULTS: A total of 421 US and 493 European patients took the study medications; 546 patients took SU and 368 took levothyroxine. Overall, 48% of patients were males; 46% were age 65 years or older. Despite most patients having received instructions on medication requirements (US 71%, EU 75%), most patients reported being only somewhat knowledgeable (US 69%; EU 71%). Adherence, measured by the proportion of the days a participant was adherent to each category out of the observational period (ranging from 3-5 days), varied by type of instruction, with the poorest adherence observed for food restriction requirements (US 34% of the observation days, EU 26%) compared to warning labels (US 77%, EU 67%) and dosing regimen (US 85%, EU 87%). CONCLUSIONS: Patients adhered to dosing and cautionary instructions across the majority of the study period but were largely non-adherent to food intake restrictions. Improved communication and increased emphasis on food intake restrictions is needed when advising patients on their medications.

Continuity of Medication Use by US Adults With Diabetes, 2005-2019.

Importance: Consistent medication use is critical for diabetes management. Population surveillance of consistency of medication use may identify opportunities to improve diabetes care. Objective: To evaluate trends in longitudinal use of glucose-, blood pressure-, and lipid-lowering medications by adults with diabetes. Design, Setting, and Participants: This serial cross-sectional study assessed trends in longitudinal use of glucose-, blood pressure-, and lipid-lowering medications by adults with diagnosed diabetes participating in the Medical Expenditure Panel Survey (MEPS), which allows serial cross-sections and 2-year longitudinal follow-up, between the 2005 to 2006 panel and 2018 to 2019 panel. Population-weighted, nationally representative estimates for the US were reported. Included individuals were adult MEPS participants with diagnosed diabetes during both years (ie, during 2005 and 2006 or during 2018 and 2019) who participated in all survey rounds. Data were analyzed from August 2021 to November 2022. Main Outcomes and Measures: Longitudinal use over the 2 years was categorized as continued use (at least 1 fill per year), no use, inconsistent use, and new use by medication type (glucose-, blood pressure-, and lipid-lowering medications). New medications were defined as prescription fills for a medication type first prescribed and filled in year 2 of MEPS participation. Results: A total of 15 237 participants with diabetes (7222 individuals aged 45-64 years [47.4%]; 8258 [54.2%] female participants; 3851 Latino [25.3%]; 3619 non-Latino Black (23.8%), and 6487 non-Latino White [42.6%]) were included in the analytical sample. A mean of 19.5% (95% CI, 18.6%-20.3%), 17.1% (95% CI, 16.2%-18.1%), and 43.3% (95% CI, 42.2%-44.3%) of participants did not maintain continuity in use of glucose-, blood pressure-, or lipid-lowering medications, respectively, during both years of follow-up. The proportion of participants who continued use of glucose-lowering medication in both years trended down from 84.5% (95% CI, 81.8%-87.3%) in 2005 to 2006 to 77.4% (95% CI, 74.8%-80.1%) in 2018 to 2019; this decrease coincided with rate increases in inconsistent use (3.3% [95% CI, 1.9%-4.7%] in 2005-2006 to 7.1% [95% CI, 5.6%-8.6%] in 2018-2019) and no use (8.1% [95% CI, 6.0%-10.1%] in 2005-2006 to 12.9% [95% CI, 10.9%-14.9%] in 2018-2019). Inconsistent use of blood pressure-lowering medications trended upward from 3.9% (95% CI, 1.8%-6.0%) in 2005 to 2006 to 9.0% (95% CI, 7.0%-11.0%) in 2016 to 2017. Inconsistent use of lipid-lowering medication trended up to a high of 9.9% (95% CI, 7.0%-12.7%) in 2017 to 2018. Conclusions and Relevance: This study found that a mean of 19.5% of participants did not maintain continuity in use of glucose-lowering medication, with recent decreases, while a mean of 17.1% and 43.2% of participants did not maintain continuity of use of blood pressure- or lipid-lowering medications, respectively.

Influence of dipeptidyl peptidase-4 inhibitors on glycemic variability in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

Objective: The influence of dipeptidyl peptidase-4 (DPP4) inhibitors on glycemic variability compared to other oral antidiabetic drugs (OADs), measured based on the mean amplitude of glycemic excursions (MAGE), has not been comprehensively analyzed. The aim of the study was to perform a meta-analysis to compare the effects of DPP4 inhibitors on MAGE with other OADs in type 2 diabetes mellitus (T2DM) patients without concurrent insulin treatments. Methods: The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant randomized controlled trials (RCTs). Study characteristics and outcome data were independently extracted by two authors. A random-effect model was used to combine the results. Results: Fourteen studies with 855 patients were included. Compared to other OADs, DPP4 inhibitors significantly reduced MAGE (mean difference [MD]: -0.69 mmol/L, 95% confidence interval [CI]: -0.95 to -0.43, P<0.001) with mild heterogeneity (I2 = 28%). Predefined subgroup analyses suggested that DPP4 inhibitors were more effective in reducing MAGE compared to insulin secretagogues (MD: -0.92 mmol/L, P<0.001) and non-secretagogues (MD: -0.43 mmol/L, P=0.02), as well as compared to sulfonylureas (MD: -0.91 mmol/L, P<0.001) and sodium glucose cotransporter 2 inhibitors (MD: -0.67 mmol/L, P=0.03). Conclusions: DPP4 inhibitors may significantly reduce glycemic variability compared to other oral anti-diabetic drugs, as evidenced by MAGE in T2DM patients with no concurrent insulin treatment. Systematic review registration: INPLASY, registration number: INPLASY2021120113.

Effect of dipeptidyl peptidase-4 inhibitors on postprandial glucagon level in patients with type 2 diabetes mellitus: A systemic review and meta-analysis.

Aims: Hyperglucagonemia occurs in the pathogenesis of type 2 diabetes mellitus (T2DM). In this meta-analysis, we summarized the effects of DPP4 inhibitors on glucagon levels in patients with T2DM. Materials and methods: Randomized controlled trials (RCTs) comparing the influence of DPP4 inhibitors on circulating glucagon levels with placebo or other oral antidiabetic drugs (OADs) in patients with T2DM were identified by searches of Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library). Only studies reporting changes in glucagon level presented as total area under the curve (AUCglucagon) using a meal or oral glucose tolerance test were included. Results were combined using a random-effects model that incorporated potential heterogeneity among the included studies. Results: A total of 36 RCTs with moderate to high quality were included. Overall, the numbers of T2DM patients included for the meta-analyses comparing DPP4 inhibitors with placebo and other OADs were 4266 and 1652, respectively. Compared to placebo, DPP4 inhibitors significantly reduced circulating glucagon levels (standard mean difference [SMD]: -0.32, 95% CI: -0.40 to -0.24, P<0.001; I2 = 28%). Analysis of subgroups revealed that study characteristics had no significant effect on results, such as study design (parallel group or crossover), number of patients, mean patient age, proportion of men, baseline HbA1c, duration of diabetes, background therapy, treatment duration, or methods for glucagon measurement (all P for subgroup differences >0.05). Moreover, DPP4 inhibitors significantly reduced glucagon levels compared to other OADs (SMD: -0.35, 95% CI: -0.53 to -0.16, P<0.001; I2 = 66%), and the reduction in glucagon was greater in comparison with insulin secretagogues than in comparison with non-insulin secretagogues (P for subgroup difference =0.03). Systematic review registration: https://inplasy.com/, identifier INPLASY202280104. Conclusions: DPP4 inhibitors are effective at reducing the circulating postprandial glucagon level in T2DM patients.

Real-world weight change, adherence, and discontinuation among patients with type 2 diabetes initiating glucagon-like peptide-1 receptor agonists in the UK.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a type 2 diabetes mellitus (T2DM) treatment with demonstrated weight loss benefits in clinical trials. However, the extent to which real-world patients with T2DM achieve clinically meaningful weight loss (≥5%) has not been well characterized. Analysis of real-world data suggests adherence to injectable GLP-1 RAs is suboptimal and discontinuation following the first year of therapy is poorly characterized. RESEARCH DESIGN AND METHODS: A retrospective cohort study among patients with T2DM initiating injectable GLP-1 RA therapy was conducted using the Clinical Practice Research Datalink that includes primary care medical records for 13 million patients in the UK. This study assessed weight change, adherence (proportion of days covered (PDC) ≥80%), and discontinuation (≥90-day gap between prescriptions) at 12 and 24 months during the study period spanning January 2009-December 2017. RESULTS: Among 589 patients initiating a GLP-1 RA, 56.4% were female and the median age was 54 years (IQR (46, 61)). The median body mass index was 41.2 kg/m2 (IQR (35.8, 46.4)). Among patients with weight measures available (n=341 at 12 months; n=232 at 24 months), 33.4% and 43.5% achieved weight loss ≥5% of baseline weight at 12 and 24 months, respectively. At 12 and 24 months, 64.5% and 59.2% were adherent, and 45.2% and 64.7% discontinued, respectively. CONCLUSIONS: A minority of patients initiating GLP-1 RAs achieved ≥5% weight loss, suggesting the real-world benefit of these agents on weight loss may be lower than that observed in clinical trials. Patients on GLP-1 RAs may benefit from additional support to improve long-term adherence.

Individualized HbA1c Goals, and Patient Awareness and Attainment of Goals in Type 2 Diabetes Mellitus: A Real-World Multinational Survey.

AIMS: While glycemic control is key in effective type 2 diabetes mellitus management, many patients fail to reach their individualized glycemic goal. This analysis aimed to describe a real-world picture of diabetes management: individualized hemoglobin A1c (HbA1c) goals, rate of goal attainment, HbA1c at each line of therapy, and patient awareness of their glycemic goal. Secondly, we aimed to understand physician satisfaction with HbA1c amongst patients aware vs. those unaware of HbA1c goal. METHODS: Analysis of physicians and the next ten consulting patients with type 2 diabetes mellitus conducted in Europe and the USA including medical record data abstraction/assessment by physicians, a patient-reported survey and a physician survey. Patients were diagnosed for 3 months or more with a known current and target HbA1c. For the sub-analysis assessment of patient awareness of HbA1c goal, in addition to the above, these patients had to have completed a patient-reported questionnaire and answer the question on awareness of HbA1c goal. RESULTS: A total of 730 physicians provided data on 8794 patients with type 2 diabetes mellitus; 5331 patients were eligible for this analysis. Overall, mean (standard deviation, SD) individualized HbA1c goal was 6.8% (0.68%). Of eligible patients, 39.1% met their HbA1c goal; of 60.9% of patients not reaching their HbA1c goal, the mean distance from individualized HbA1c goal was 0.9% (SD 1.0%). Physicians progressed patients' antihyperglycemic therapy when HbA1c was 8% or higher. Among 2560 patients who were included in the sub-analysis assessing the effect of patient awareness of their HbA1c goal on multiple parameters, 70.5% were aware of their HbA1c goal; mean HbA1c goal was 6.8% (0.7%) and current mean HbA1c value 7.1% (1.2%). A total of 949 patients in the sub-analysis (39.2%) achieved their goal; achieving HbA1c goal was not related to knowledge of goal. Patients aware of their HbA1c goal were slightly more adherent to their antihyperglycemic medication. They also were prescribed more antihyperglycemic agents, more often on a later therapy line receiving a GLP-1 receptor agonist, SGLT2i, or insulin, and more often tested their blood glucose levels than patients who were unaware. Physicians were not satisfied with the current blood glucose level of one third of their patients, believing that more of those who were aware of their HbA1c goal could achieve better glucose control (32.4% of aware vs. 28.2% of unaware patients; p = 0.003). CONCLUSIONS: Our results showed that the proportion of patients with type 2 diabetes mellitus achieving their goals for glycemic control was suboptimal when compared to current guideline criteria, with only about 40% of patients achieving their individualized HbA1c goal. Treatment intensification was often delayed until HbA1c was 8% and higher. Patients aware of their HbA1c goal were slightly more adherent to their antihyperglycemic medication; however, awareness of HbA1c goal did not enhance goal attainment. This highlights the need for a holistic approach to diabetes management, involving patient education, and patient-physician communication and partnership.

Trends and Variations in Emergency Department Use Associated With Diabetes in the US by Sociodemographic Factors, 2008-2017.

Importance: Little is known about emergency department (ED) use among people with diabetes and whether the pattern of ED use varies across geographic areas and population subgroups. Objective: To estimate recent national- and state-level trends in diabetes-related ED use overall and by race and ethnicity, rural or urban location, and insurance status. Design, Setting, and Participants: This cross-sectional study of adults visiting the ED with a diabetes-related diagnosis used serial data from the Nationwide Emergency Department Sample, a nationally representative database, and discharge records from 11 state emergency department databases for 2008, 2011, 2014, and 2016 to 2017. Data were analyzed from March 16 to November 9, 2020. Exposures: Reported race and ethnicity, rural or urban location, and insurance status. Data were stratified to generate state-specific estimates. Main Outcomes and Measures: Rates of ED use for all-cause visits among adults with diabetes (all-cause diabetes visits) and visits with primary diagnoses of diabetes-specific complications. Results: A larger portion of all-cause diabetes ED visits (n = 32 433 015) were by female (56.8%) and middle-aged (mean [SD] age, 58.4 [16.3] years) adults with diabetes. Nationally, all-cause diabetes ED visits per 10 000 adults increased 55.6% (95% CI, 50.6%-60.6%), from 257.6 (95% CI, 249.9-265.3) visits in 2008 to 400.8 (95% CI, 387.6-414.0) visits in 2017. All-cause diabetes ED visits increased more for urban (58.3%; 95% CI, 52.5%-64.1%) and uninsured subgroups (75.3% [95% CI, 59.8%-90.8%]) than for their counterparts. Diabetes-specific ED visits (weighted number of 1 911 795) nationally increased slightly among all subgroups. State-specific ED use rates show wide state-to-state variations in ED use by race and ethnicity, rural or urban location, and insurance. On average across states, diabetes-specific ED use among Black patients was approximately 3 times (rate ratio, 3.09 [95% CI, 2.91-3.30]) greater than among non-Hispanic White patients, and among Hispanic patients, it was 29% greater (rate ratio, 1.29 [95% CI, 1.19-1.40]) than among non-Hispanic White patients. The mean rate of ED use among rural patients was 34% greater (rate ratio, 1.34 [95% CI, 1.26-1.44]) than among urban patients. The mean rates of ED use among patients with Medicaid (rate ratio, 6.65 [95% CI, 6.49-6.82]) and Medicare (rate ratio, 4.37 [95% CI, 4.23-4.51]) were greater than among privately insured adults. Conclusions and Relevance: This study suggests that disparities in diabetes-related ED use associated with race and ethnicity, rural or urban location, and insurance status were persistent from 2008 to 2017 within and across states, as well as nationally. Further geographic and demographic-specific analyses are needed to understand the sources of inequity.

Trends and Demographic Disparities in Diabetes Hospital Admissions: Analyses of Serial Cross-Sectional National and State Data, 2008-2017.

OBJECTIVE: To analyze national and state-specific trends in diabetes-related hospital admissions and determine whether disparities in rates of admission exist between demographic groups and geographically dispersed states. RESEARCH DESIGN AND METHODS: We conducted serial cross-sectional analyses of the National Inpatient Sample (2008, 2011, 2014, and 2016) and State Inpatient Databases for Arizona, Florida, Kentucky, Iowa, Maryland, Nebraska, New Jersey, New York, North Carolina, Utah, and Vermont for 2008, 2011, 2014, and 2016/2017 among adult patients with type 1 and type 2 diabetes-related ICD codes (ICD-9 [250.XX] or ICD-10 [E10.XXX, E11.XXX, and E13.XXX]. We measured hospitalization rates for people with diabetes (all-cause hospitalizations) and for admissions with a primary diagnosis of diabetes or diabetes-related complications (diabetes-specific hospitalizations) per 10,000 people per year. RESULTS: Nationally, all-cause and diabetes-specific hospitalizations declined by 3.1% (95% CI -5.5, -0.7) and 19.1% (95% CI -21.6, -16.6), respectively, over 2008 to 2016. The analysis of individual states showed that diabetes-specific admissions in individuals ≥65 years old declined during this time (16.3-48.8% decrease) but increased among patients 18-29 years old (10.5-81.5% increase) and that rural diabetes-specific admissions decreased in just over half of the included states (15.2-69.2% decrease). There were no differences in changes in admission rates among different racial/ethnic groups. CONCLUSIONS: Overall, rates of diabetes-related hospitalizations decreased over 2008 to 2016/2017, but there were large state-level differences across subgroups of patients. The rise in diabetes hospitalizations among young adults is a cause for concern. These state- and subpopulation-level differences highlight the need for state-level policies and interventions to address disparities in diabetes health care use.