Therapeutic Inertia and Delays in Insulin Intensification in Type 2 Diabetes: A Literature Review.

Background: Therapeutic inertia leading to delays in insulin initiation or intensification is a major contributor to lack of optimal diabetes care. This report reviews the literature summarizing data on therapeutic inertia and delays in insulin intensification in the management of type 2 diabetes. Methods: A literature search was conducted of the Allied & Complementary Medicine, BIOSIS Previews, Embase, EMCare, International Pharmaceutical Abstracts, MEDLINE, and ToxFile databases for clinical studies, observational research, and meta-analyses from 2012 to 2022 using search terms for type 2 diabetes and delay in initiating/intensifying insulin. Twenty-two studies met inclusion criteria. Results: Time until insulin initiation among patients on two to three antihyperglycemic agents was at least 5 years, and mean A1C ranged from 8.7 to 9.8%. Early insulin intensification was linked with reduced A1C by 1.4%, reduction of severe hypoglycemic events from 4 to <1 per 100 person-years, and diminution in risk of heart failure (HF) by 18%, myocardial infarction (MI) by 23%, and stroke by 28%. In contrast, delayed insulin intensification was associated with increased risk of HF (64%), MI (67%), and stroke (51%) and a higher incidence of diabetic retinopathy. In the views of both patients and providers, hypoglycemia was identified as a primary driver of therapeutic inertia; 75.5% of physicians reported that they would treat more aggressively if not for concerns about hypoglycemia. Conclusion: Long delays before insulin initiation and intensification in clinically eligible patients are largely driven by concerns over hypoglycemia. New diabetes technology that provides continuous glucose monitoring may reduce occurrences of hypoglycemia and help overcome therapeutic inertia associated with insulin initiation and intensification.

Trends in Time in Range-Related Publications and Clinical Trials: A Bibliometric Review.

Objective: The goal of this article was to describe trends in publications (including conference abstracts) and clinical trials that report on glycemic time in range (TIR). Data sources: Reviewed databases included but were not limited to MEDLINE and Embase. Clinical trial registries were also sourced. Study selection: All studies reporting TIR published between 2010 and 2021 were included. Clinical trials reporting TIR that started in or after 2010 were also included. Non-English publications, abstracts, and clinical trials were excluded. Book chapters, nonhuman studies, and studies not reporting TIR were excluded. Data extraction: Manuscript/abstract category, publication year, study region, interventional versus observational role of continuous glucose monitoring (CGM), and clinical trial start and completion dates were captured. Glycemic outcomes reported in publications or trials, including TIR as a primary outcome, A1C, time below range (TBR), and time above range (TAR), were also captured. Results: A total of 373 clinical trials, 531 publications, and 620 abstracts were included in the review. The number of trials, publications, and abstracts reporting TIR significantly increased, particularly between 2018 and 2021, during which time the number of clinical trials, publications, and conference abstracts reporting TIR increased by 6-fold, 12-fold, and 4.5-fold, respectively. About 35-44% of studies reported TIR as a primary outcome. Approximately 54% of clinical trials, 47% of publications, and 47% of conference abstracts reported the role of CGM to be observational. TBR was reported more often than TAR. Conclusion: The marked increase in the number of trials, publications, and abstracts reporting TIR highlights the increasing significance and acceptance of TIR as an outcome measure in diabetes management.

Efficacy and safety of a medication dose reminder feature in a digital health offering with the use of sensor-enabled medicines.

OBJECTIVES: Over one-half of patients with chronic diseases, such as hypertension and type 2 diabetes (DM), do not take medicines as prescribed. This study assessed the efficacy and safety of "seeing" versus "not seeing" medication dose reminders regarding medication adherence and risk for overdose. DESIGN: Post hoc analysis. SETTING AND PARTICIPANTS: Outpatient setting. Adult subjects (18 years of age or older) with uncontrolled hypertension and DM. MAIN OUTCOME MEASURES: Subjects enrolled in this institutional review board-approved study were assigned to either use digital health (DH) with the use of sensor-enabled medicines (coencapsulated medicines with an ingestible sensor) for 4 or 12 weeks or receive usual care based on a cluster-randomized design. All subjects were followed for 12 weeks. Subjects using DH were included in the post hoc study consisting of an efficacy analysis and a safety analysis. A main efficacy outcome of comparison of subjects taking medicine with or without "seeing" DH medication dose reminders was assessed. Safety analysis assessed risk of overdosing after DH medication dose reminders. RESULTS: In 57 subjects included in the efficacy analysis, DH device reminder messages were associated with a 16 ± 16% increase (75 ± 18% when seeing vs. 59 ± 24% when not seeing mobile dose reminders) in medication taking if not taken before dose reminder. The mean overall adherence for all subjects was 86 ± 12%; the mean on-time adherence was 69.7 ± 19.7%. Subjects with lower adherence benefited more from seeing DH reminder messages. In the safety study (n = 74 subjects and 24,426 medication ingestions), no events of overdoses related to DH medication dose reminders occurred. CONCLUSION: This study demonstrates benefits of DH medication dose reminders to improve medication adherence, especially in patients with lower adherence; DH medication dose reminders also appear to be safe.

Association of self-monitoring of blood glucose use on glycated hemoglobin and weight in newly diagnosed, insulin-naïve adult patients with type 2 diabetes.

BACKGROUND: Clinical trials have shown that self-monitoring of blood glucose (SMBG) combined with patient education and medication titration can lead to improved glycated hemoglobin (HbA1c) and reduced weight in recently diagnosed non-insulin-treated type 2 diabetes mellitus (T2DM) patients. This retrospective matched cohort study assessed the association of SMBG with achieving long-term clinical outcomes in these patients in a real-world clinical setting. METHODS: Using electronic medical records (2008-2011), we selected a population of adult patients recently diagnosed with T2DM not receiving insulin who were SMBG users and a population of non-SMBG controls with similar demographic and clinical characteristics using propensity score matching. The main study outcomes compared between the two groups were time to achieve (1) HbA1c <7% for patients with baseline HbA1c ≥ 7% and (2) a ≥ 5% reduction in weight from baseline. RESULTS: Of the 589 patients identified in each group, 113 in each group had a baseline HbA1c ≥ 7% (mean, 8.2%). The SMBG users were more likely to achieve an HbA1c <7% (12 months: 58.4% versus 38.9%, p = .0037; 36 months: 84.0% versus 70.0%, p = .0013) and to do so faster (median, 6.5 versus 20.5 months; log-rank p = .0016). Self-monitoring of blood glucose was associated with faster weight reduction (median time to achieve a ≥ 5% reduction, 23.5 versus 35.9 months for SMBG and non-SMBG, respectively; log-rank p = .0005). CONCLUSIONS: In newly diagnosed T2DM insulin-naïve patients, SMBG users had an improved rate of achieving long-term glycemic control and weight loss in a real-world clinical setting.

Importance of blood glucose meter and carbohydrate estimation accuracy.

BACKGROUND: The clinical significance of blood glucose meter (BGM) error in the presence of increasing carbohydrate errors in diabetes patients who use both the BGM result and the carbohydrate estimation to dose insulin is unknown. METHODS: This Monte Carlo simulation modeled diabetes patients who calculate insulin dosages based on BGM results and carbohydrate estimations. It evaluated the likelihood of on-target insulin dosing and clinically significant insulin dose errors based on data from five BGMs with different levels of performance (expressed as bias and imprecision [coefficient of variation (%CV)]) and increasing levels of carbohydrate estimation errors. The study was performed across three separate preprandial glucose (PPG) ranges (90-150, 150-270, and 270-450 mg/dl). RESULTS: When carbohydrate estimation is accurate (%CV = 0%), the likelihood for on-target insulin doses ranged 50.1-98.5%. The likelihood depended on BGM performance and PPG range. In the presence of carbohydrate estimation errors (%CV = 5-20%), the likelihood of on-target insulin dosages markedly decreased (range, 27.2-80.1%) for all BGMs, the likelihood of insulin underdosing (range, 0-12.8%) and overdosing (range, 0-32.3%) increased, and the influence of BGM error on insulin dosing accuracy was blunted. Even in the presence of carbohydrate error, the BGM with the best performance (bias 1.35% and %CV = 4.84) had the highest probability for on-target insulin dosages. CONCLUSIONS: Both BGM and carbohydrate estimation error contribute to insulin dosing inaccuracies. The BGM with the best performance was associated with the most on-target insulin dosages.

Association between sitagliptin adherence and self-monitoring of blood glucose.

BACKGROUND: We evaluated the association between self-monitoring of blood glucose (SMBG) use and sitagliptin or sitagliptin/metformin (SSMT) adherence. SSMT was chosen as these medications have little risk of hypoglycemia and are believed to not require SMBG data for titration. METHODS: This was an observational study using data extracted from a large United States insurance claims database (i3 InVision™ Data Mart, Ingenix, Inc.). Data were extracted on noninsulin-using patients initiating SSMT for each 12-month period pre- and post-SSMT initiation. Logistic regression was used to assess the relationship between SMBG use and the likelihood of being medication adherent (defined as a medication possession ratio of ≥75%) while controlling for covariates. RESULTS: This analysis included 7,306 patients (57.6% male; mean age 54.2 years). Mean pre-SSMT hemoglobin A1c (HbA1c) was 8.0%. In the post-SSMT initiation period, 58% of patients were adherent with SSMT. Older age, male gender, prior use of oral diabetes medication, and lower HbA1c were associated with improved SSMT adherence. SMBG use was associated with improved adherence [odds ratio (OR) ranged from 1.198 to 1.338; p < .05] compared with patients with no SMBG use pre- or post-SSMT initiation. For patients who began SMBG after starting SSMT, greater SMBG use was associated with better adherence (OR 1.449 for higher vs 1.246 for lower strip use; p < .05). CONCLUSIONS: This study demonstrated that SMBG is associated with improved SSMT adherence. This relationship is strengthened with greater SMBG use.