The TransFORmation of IndiGEnous PrimAry HEAlthcare Delivery (FORGE AHEAD): economic analysis.

BACKGROUND: Indigenous populations have increased risk of developing diabetes and experience poorer treatment outcomes than the general population. The FORGE AHEAD program partnered with First Nations communities across Canada to improve access to resources by developing community-driven primary healthcare models. METHODS: This was an economic assessment of FORGE AHEAD using a payer perspective. Costs of diabetes management and complications during the 18-month intervention were compared to the costs prior to intervention implementation. Cost-effectiveness of the program assessed incremental differences in cost and number of resources utilization events (pre and post). Primary outcome was all-cause hospitalizations. Secondary outcomes were specialist visits, clinic visits and community resource use. Data were obtained from a diabetes registry and published literature. Costs are expressed in 2023 Can$. RESULTS: Study population was ~ 60.5 years old; 57.2% female; median duration of diabetes of 8 years; 87.5% residing in non-isolated communities; 75% residing in communities < 5000 members. Total cost of implementation was $1,221,413.60 and cost/person $27.89. There was increase in the number and cost of hospitalizations visits from 8/$68,765.85 (pre period) to 243/$2,735,612.37. Specialist visits, clinic visits and community resource use followed this trend. CONCLUSION: Considering the low cost of intervention and increased care access, FORGE AHEAD represents a successful community-driven partnership resulting in improved access to resources.

The Determination of Diabetes Utilities, Costs, and Effects Model: A Cost-Utility Tool Using Patient-Level Microsimulation to Evaluate Sensor-Based Glucose Monitoring Systems in Type 1 and Type 2 Diabetes: Comparative Validation.

OBJECTIVES: To assess the accuracy and validity of the Determination of Diabetes Utilities, Costs, and Effects (DEDUCE) model, a Microsoft-Excel-based tool for evaluating diabetes interventions for type 1 and type 2 diabetes. METHODS: The DEDUCE model is a patient-level microsimulation, with complications predicted based on the Sheffield and Risk Equations for Complications Of type 2 diabetes models for type 1 and type 2 diabetes, respectively. For this tool to be useful, it must be validated to ensure that its complication predictions are accurate. Internal, external, and cross-validation was assessed by populating the DEDUCE model with the baseline characteristics and treatment effects reported in clinical trials used in the Fourth, Fifth, and Ninth Mount Hood Diabetes Challenges. Results from the DEDUCE model were evaluated against clinical results and previously validated models via mean absolute percentage error or percentage error. RESULTS: The DEDUCE model performed favorably, predicting key outcomes, including cardiovascular disease in type 1 diabetes and all-cause mortality in type 2 diabetes. The model performed well against other models. In the Mount Hood 9 Challenge comparison, error was below the mean reported from comparator models for several outcomes, particularly for hazard ratios. CONCLUSIONS: The DEDUCE model predicts diabetes-related complications from trials and studies well when compared with previously validated models. The model may serve as a useful tool for evaluating the cost-effectiveness of diabetes technologies.

Urinary Vitamin D Binding Protein: A Marker of Kidney Tubular Dysfunction in Patients at Risk for Type 2 Diabetes.

Context: Recent studies have reported elevated urinary vitamin D binding protein (uVDBP) concentrations in patients with diabetic kidney disease, although the utility of uVDBP to predict deterioration of kidney function over time has not been examined. Objective: Our objective was to assess the association of uVDBP with longitudinal changes in kidney function. Methods: Adults at-risk for type 2 diabetes from the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 727). Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used as measures of kidney function. Measurements of uVDBP were performed with enzyme-linked immunosorbent assay and normalized to urine creatinine (uVDBP:cr). Generalized estimating equations (GEEs) evaluated longitudinal associations of uVDBP and uVDBP:cr with measures of kidney function, adjusting for covariates. Results: Renal uVDBP loss increased with ACR severity at baseline. Individuals with normoalbuminuria, microalbuminuria, and macroalbuminuria had median log uVDBP:cr concentrations of 1.62 µg/mmol, 2.63 µg/mmol, and 2.48 µg/mmol, respectively, and ACR positively correlated with uVDBP concentrations (r = 0.37; P < .001). There was no significant association between uVDBP and eGFR at baseline. Adjusted longitudinal GEE models indicated that each SD increase both in baseline and longitudinal uVDBP:cr was significantly associated with higher ACR over 6 years (ß = 30.67 and ß = 32.91, respectively). Conversely, neither baseline nor longitudinal uVDBP:cr measures showed a significant association with changes in eGFR over time. These results suggest that loss of uVDBP:cr over time may be a useful marker for predicting renal tubular damage in individuals at risk for diabetes.

Determinants of Anishinabeck infant and early childhood growth trajectories in Northwestern Ontario, Canada: a cohort study.

BACKGROUND: The Developmental Origins of Health and Disease (DOHaD) paradigm emphasizes the significance of early life factors for the prevention of chronic health conditions, like type 2 diabetes (T2DM) and obesity, which disproportionately affect First Nations communities in Canada. Despite increasing DOHaD research related to maternal health during pregnancy, early childhood growth patterns, and infant feeding practices with many populations, data from First Nations communities in Canada are limited. In partnership with Sandy Lake First Nation, the aims of this project were to characterize birthweights and growth patterns of First Nations infants/children over the first 6 years of life and to study the impact of maternal and infant social and behavioral factors on birthweight and growth trajectories. METHODS: We recruited 194 families through community announcements and clinic visits. Infant/child length/height and weight were measured at 1 and 2 weeks; 1, 2, 6, 12, and 18 months; and 2, 3, 4, 5 and 6 years. Maternal and infant/child questionnaires captured data about health, nutrition, and social support. Weight-for-Age z-score (WAZ), Height-for-Age z-score (HAZ), and BMI-for-Age z-score (BAZ) were calculated using WHO reference standards and trajectories were analyzed using generalized additive models. Generalized estimating equations and logistic regression were used to determine associations between exposures and outcomes. RESULTS: WAZ and BAZ were above the WHO mean and increased with age until age 6 years. Generalized estimating equations indicated that WAZ was positively associated with age (0.152; 95% CI 0.014, 0.29), HAZ was positively associated with birthweight (0.155; 95% CI 0.035, 0.275), and BAZ was positively associated with caregiver's BMI (0.049; 95% CI 0.004, 0.090). There was an increased odds of rapid weight gain (RWG) with exposure to gestational diabetes (OR: 7.47, 95% CI 1.68, 46.22). Almost 70% of parents initiated breastfeeding, and breastfeeding initiation was modestly associated with lower WAZ (-0.18; 95% CI -0.64, 0.28) and BAZ (-0.23; 95% CI -0.79, 0.34). CONCLUSIONS: This work highlights early life factors that may contribute to T2DM etiology and can be used to support community and Indigenous-led prevention strategies.

Severe (level 3) hypoglycaemia occurrence in a real-world cohort of adults with type 1 or 2 diabetes mellitus (iNPHORM, United States).

AIMS: Among adults with insulin- and/or secretagogue-treated diabetes in the United States, very little is known about the real-world descriptive epidemiology of iatrogenic severe (level 3) hypoglycaemia. Addressing this gap, we collected primary, longitudinal data to quantify the absolute frequency of events as well as incidence rates and proportions. MATERIALS AND METHODS: iNPHORM is a US-wide, 12-month ambidirectional panel survey (2020-2021). Adults with type 1 diabetes mellitus (T1DM) or insulin- and/or secretagogue-treated type 2 diabetes mellitus (T2DM) were recruited from a probability-based internet panel. Participants completing ≥1 follow-up questionnaire(s) were analysed. RESULTS: Among 978 respondents [T1DM 17%; mean age 51 (SD 14.3) years; male: 49.6%], 63% of level 3 events were treated outside the health care system (e.g. by family/friend/colleague), and <5% required hospitalization. Following the 12-month prospective period, one-third of individuals reported ≥1 event(s) [T1DM 44.2% (95% CI 36.8%-51.8%); T2DM 30.8% (95% CI 28.7%-35.1%), p = .0404, α = 0.0007]; and the incidence rate was 5.01 (95% CI 4.15-6.05) events per person-year (EPPY) [T1DM 3.57 (95% CI 2.49-5.11) EPPY; T2DM 5.29 (95% CI 4.26-6.57) EPPY, p = .1352, α = 0.0007]. Level 3 hypoglycaemia requiring non-transport emergency medical services was more common in T2DM than T1DM (p < .0001, α = 0.0016). In total, >90% of events were experienced by <15% of participants. CONCLUSIONS: iNPHORM is one of the first long-term, prospective US-based investigations on level 3 hypoglycaemia epidemiology. Our results underscore the importance of participant-reported data to ascertain its burden. Events were alarmingly frequent, irrespective of diabetes type, and concentrated in a small subsample.

Patient and physician perspectives and experiences of basal insulin titration in type 2 diabetes in the United States: Cross-sectional surveys.

AIM: Patient- and physician-associated barriers impact the effectiveness of basal insulin (BI) titration in the management of type 2 diabetes (T2D). We evaluated the experiences of patients with T2D and physicians with BI titration education. MATERIALS AND METHODS: In this observational, cross-sectional study, patients with T2D and physicians treating patients with T2D were identified by claims in the Optum Research Database and were invited to complete a survey. Eligible patients had 12 months of continuous health-plan enrolment with medical and pharmacy benefits during the baseline period, and recent initiation of BI therapy. Eligible physicians had initiated BI for ≥1 eligible patient with T2D during the past 6 months. RESULTS: In total, 416 patients and 386 physicians completed the survey. Ninety per cent of physicians reported treating ≥50 patients with T2D; 66% treated ≥25% of patients with BI. Whereas 74% of patients reported that BI titration was explained to them by a physician, 96% of physicians reported doing so. Furthermore, 20% of patients stated they were offered educational materials whereas 56% of physicians reported having provided materials. Physicians had higher expectations of glycaemic target achievement than were seen in the patient survey; their main concern was the patients' ability to titrate accurately (79%). CONCLUSIONS: There is a marked difference in patients' and physicians' experiences of BI titration education. Novel tools and strategies are required to enable effective BI titration, with more educational resources at the outset, and ongoing access to tools that provide clear, simple direction for self-titration with less reliance on physicians/health care providers.

Association of Serum Very-Long-Chain Saturated Fatty Acids With Changes in Insulin Sensitivity and ß-Cell Function: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) Cohort.

A unique group of circulating very-long-chain saturated fatty acids (VLCSFAs), including arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have been associated with a lower risk of type 2 diabetes, although associations with early metabolic risk phenotypes preceding type 2 diabetes have received limited study. We aimed to examine the associations of VLCSFAs with longitudinal changes in insulin sensitivity and ß-cell function in a cohort at risk for type 2 diabetes. VLCSFAs in the four main serum pools (phospholipid, triacylglycerol, cholesteryl ester, and nonesterified fatty acid) were extracted from fasting baseline samples (n = 467). Generalized estimating equations were used to determine the associations between VLCSFAs and changes over 9 years in validated indices of insulin sensitivity (HOMA2-%S [insulin sensitivity as percentage of normal population and ISI) and ß-cell function (insulinogenic index [IGI], IGI divided by HOMA-insulin resistance [IGI/IR], and insulin secretion sensitivity index 2 [ISSI-2]). Associations of VLCSFAs with outcomes were strongest in the triacylglycerol lipid pool: 20:0 was positively associated with both insulin sensitivity and ß-cell function (5.01% increase in HOMA2-%S and 4.01-6.28% increase in IGI/IR and ISSI-2 per SD increase in 20:0); 22:0 was positively associated with insulin sensitivity, with a 6.55% increase in HOMA2-%S and a 5.80% increase in ISI per SD increase in 22:0. Lastly, 24:0 was positively associated with insulin sensitivity and ß-cell function (7.94-8.45% increase in HOMA2-%S and ISI, and a 4.61-6.93% increase in IGI/IR and ISSI-2 per SD increase in 24:0). Fewer significant associations were observed in the cholesteryl ester and nonesterified pools. Overall, our results indicate positive longitudinal associations of VLCSFAs with insulin sensitivity and ß-cell function, especially within the triacylglycerol pool.

Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial.

AIM: Non-surgical options for inducing type 2 diabetes remission are limited. We examined whether remission can be achieved by combining lifestyle approaches and short-term intensive glucose-lowering therapy. METHODS: In this trial, 160 patients with type 2 diabetes on none to two diabetes medications other than insulin were randomised to (a) an intervention comprising lifestyle approaches, insulin glargine/lixisenatide and metformin, or (b) standard care. Participants with glycated haemoglobin (HbA1c) <7.3% (56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for an additional 52 weeks. The primary outcome was diabetes relapse defined as HbA1c ≥6.5% (48 mmol/mol) at 24 weeks or thereafter, capillary glucose ≥10 mmol/L on ≥50% of readings, or use of diabetes medications, analysed as time-to-event. Main secondary outcomes included complete or partial diabetes remission at 24, 36, 48 and 64 weeks defined as HbA1c <6.5% (48 mmol/mol) off diabetes medications since 12 weeks after randomisation. A hierarchical testing strategy was applied. RESULTS: The intervention significantly reduced the hazard of diabetes relapse by 43% (adjusted hazard ratio 0.57, 95% confidence interval 0.40-0.81; p = .002). Complete or partial diabetes remission was achieved in 30 (38.0%) intervention group participants versus 16 (19.8%) controls at 24 weeks and 25 (31.6%) versus 14 (17.3%) at 36 weeks [relative risk 1.92 (95% confidence interval 1.14-3.24) and 1.83 (1.03-3.26), respectively]. The relative risk of diabetes remission in the intervention versus control group was 1.88 (1.00-3.53) at 48 weeks and 2.05 (0.98-4.29) at 64 weeks. CONCLUSIONS: A 12-week intensive intervention comprising insulin glargine/lixisenatide, metformin and lifestyle approaches can induce remission of diabetes.

Development and validation of a real-world model to predict 1-year Level 3 (severe) hypoglycaemia risk in adults with diabetes (the iNPHORM study, United States).

AIMS: We aimed to develop and internally validate a real-world prognostic model for Level 3 hypoglycaemia risk compatible with outpatient care in the United States. MATERIALS AND METHODS: iNPHORM is a 12-month, US-based panel survey. Adults (18-90 years old) with type 1 diabetes mellitus or insulin- and/or secretagogue-treated type 2 diabetes mellitus were recruited from a nationwide, probability-based internet panel. Among participants completing ≥ 1 follow-up questionnaire(s), we modelled 1-year Level 3 hypoglycaemia risk using Andersen and Gill's Cox survival and penalized regression with multiple imputation. Candidate variables were selected for their clinical relevance and ease of capture at point-of-care. RESULTS: In total, 986 participants [type 1 diabetes mellitus: 17%; men: 49.6%; mean age: 51 (SD: 14.3) years] were analysed. Across follow-up, 035.1 (95% CI: 32.2-38.1)% reported ≥1 Level 3 event(s), and the rate was 5.0 (95% CI: 4.1-6.0) events per person-year. Our final model showed strong discriminative validity and parsimony (optimism corrected c-statistic: 0.77). Numerous variables were selected: age; sex; body mass index; marital status; level of education; insurance coverage; race; ethnicity; food insecurity; diabetes type; glycated haemoglobin value; glycated haemoglobin variability; number, type and dose of various medications; number of SH events requiring hospital care (past year and over follow-up); type and number of comorbidities and complications; number of diabetes-related health care visits (past year); use of continuous/flash glucose monitoring; and general health status. CONCLUSIONS: iNPHORM is the first US-based primary prognostic study on Level 3 hypoglycaemia. Future model implementation could potentiate risk-tailored strategies that reduce real-world event occurrence and overall diabetes burden.

Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes.

In early type 2 diabetes, the strategy of "induction" with short-term intensive insulin therapy followed by "maintenance" with metformin can stabilize pancreatic beta-cell function in some patients but not others. We thus sought to elucidate determinants of sustained stabilization of beta-cell function. In this secondary analysis of ClinicalTrials.Gov NCT02192424, adults with ≤5-years diabetes duration were randomized to 3-weeks induction insulin therapy (glargine/lispro) followed by metformin maintenance either with or without intermittent 2-week courses of insulin every 3-months for 2-years. Sustained stabilization (higher beta-cell function at 2-years than at baseline) was achieved in 55 of 99 participants. Independent predictors of sustained stabilization were the change in beta-cell function during induction and changes in hepatic insulin resistance and alanine aminotransferase during maintenance. Thus, initial reversibility of beta-cell dysfunction during induction and subsequent preservation of hepatic insulin sensitivity during maintenance are associated with sustained stabilization of beta-cell function following short-term insulin and metformin.ClinicalTrials.Gov NCT02192424.

Real-World Effects of Second-Generation Versus Earlier Intermediate/Basal Insulin Analogues on Rates of Hypoglycemia in Adults with Type 1 and 2 Diabetes (iNPHORM, US).

INTRODUCTION: Second-generation basal insulin analogues have been shown to reduce hypoglycemia in several trials and observational studies of select populations; however, it remains unclear whether these results persist in real-world settings. Using self-reported hypoglycemia events, we assessed whether second-generation basal insulin analogues reduce rates of hypoglycemia events (non-severe/severe; overall/daytime/nocturnal) compared to earlier intermediate/basal insulin analogues among people with insulin-treated type 1 or 2 diabetes. METHODS: We used prospectively collected data from the Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-World Models (iNPHORM) panel survey. This US-wide, 1-year internet-based survey assessed hypoglycemia experiences and related sociodemographic and clinical characteristics of people with diabetes (February 2020-March 2021). We estimated population-average rate ratios for hypoglycemia comparing second-generation to earlier intermediate/basal insulin analogues using negative binomial regression, adjusting for confounders. Within-person variability of repeated observations was addressed with generalized estimating equations. RESULTS: Among iNPHORM participants with complete data, N = 413 used an intermediate/basal insulin analogue for ≥ 1 month during follow-up. After adjusting for baseline and time-updated confounders, average second-generation basal insulin analogue users experienced a 19% (95% CI 3-32%, p = 0.02) lower rate of overall non-severe hypoglycemia and 43% (95% CI 26-56%, p < 0.001) a lower rate of nocturnal non-severe hypoglycemia compared to earlier intermediate/basal insulin users. Overall severe hypoglycemia rates were similar among second-generation and earlier intermediate/basal insulin users (p = 0.35); however, the rate of severe nocturnal hypoglycemia was reduced by 44% (95% CI 10-65%, p = 0.02) among second-generation insulin users compared to earlier intermediate/basal insulin users. CONCLUSION: Our real-world results suggest second-generation basal insulin analogues reduce rates of hypoglycemia, especially nocturnal non-severe and severe events. Whenever possible and feasible, clinicians should prioritize prescribing these agents over first-generation basal or intermediate insulin in people with type 1 and 2 diabetes.

Association of circulating branched chain fatty acids with insulin sensitivity and beta cell function in the PROMISE cohort.

Branched chain fatty acids (BCFAs) are mainly saturated fatty acids with a methyl branch on the penultimate or antepenultimate carbon atom. While BCFAs are endogenously produced via the catabolism of branched chain amino acids, the primary exogenous source of BCFAs in the human body is via the diet, including dairy products. Recently, BCFAs have been identified as having a potentially protective role in the etiology of cardiometabolic disorders although current literature is limited. We aimed to investigate the longitudinal associations of circulating BCFAs across four serum pools with insulin sensitivity, beta cell function, and glucose concentrations in the PROMISE Cohort. Estimates of insulin sensitivity were assessed using Matsuda's insulin sensitivity index (ISI) and the homeostasis model assessment of insulin sensitivity (HOMA2). Estimates of beta cell function were determined using the insulinogenic index divided by HOMA insulin resistance and the insulin secretion-sensitivity index-2 (ISSI-2). Baseline serum samples were analyzed for BCFAs using gas-chromatography flame ionization detection. Longitudinal associations were determined using generalized estimating equations. In the free fatty acid (FFA) pool, iso15:0 and anteiso15:0 were positively associated with logHOMA2 (iso15:0 logHOMA2-%S: ß = 6.86, 95% CI: [1.64, 12.36], p < 0.05, anteiso15:0 logHOMA2-%S: ß = 6.36, 95% CI: [0.63, 12.42], p < 0.05) while anteiso14:0 was inversely associated with measures of insulin sensitivity (iso14:0 logHOMA2-%S: ß = -2.35, 95% CI: [-4.26, -0.40], p < 0.05, logISI: ß = -2.30, 95% CI: [-4.32, -0.23], p < 0.05, anteiso14:0 logHOMA2-%S: ß = -4.72, 95% CI: [-7.81, -1.52], p < 0.05, logISI: ß = -6.13, 95% CI: [-9.49, -2.66], p < 0.01). Associations in other pools were less consistent. We identified the potential importance of specific BCFAs, specifically iso14:0, anteiso14:0, iso15:0, anteiso15:0, in cardiometabolic phenotypes underlying type 2 diabetes.

Exploring quality improvement for diabetes care in First Nations communities in Canada: a multiple case study.

BACKGROUND: Indigenous peoples in Canada experience higher rates of diabetes and worse outcomes than non-Indigenous populations in Canada. Strategies are needed to address underlying health inequities and improve access to quality diabetes care. As part of the national FORGE AHEAD Research Program, this study explores two primary healthcare teams' quality improvement (QI) process of developing and implementing strategies to improve the quality of diabetes care in First Nations communities in Canada. METHODS: This study utilized a community-based participatory and qualitative case study methodology. Multiple qualitative data sources were analyzed to understand: (1) how knowledge and information was used to inform the teams' QI process; (2) how the process was influenced by the context of primary care services within communities; and (3) the factors that supported or hindered their QI process. RESULTS: The findings of this study demonstrate how teams drew upon multiple sources of knowledge and information to inform their QI work, the importance of strengthening relationships and building relationships with the community, the influence of organizational support and capacity, and the key factors that facilitated QI efforts. CONCLUSIONS: This study contributes to the ongoing calls for research in understanding the process and factors affecting the implementation of QI strategies, particularly within Indigenous communities. The knowledge generated may help inform community action and the future development, implementation and scale-up of QI programs in Indigenous communities in Canada and globally.

Impact of the COVID-19 Pandemic on Antihyperglycemic Prescriptions for Adults With Type 2 Diabetes in Canada: A Cross-sectional Study.

OBJECTIVES: Diabetes is a major public health problem in Canada and requires multifactorial, consistent clinical management. The COVID-19 pandemic has increased challenges in the management of many chronic ailments, including diabetes. Diabetes was associated with a higher risk of severe illness in the context of COVID-19. Pandemic restrictions also impacted diabetes care continuity, which may have contributed to an increased risk of diabetes-related complications and mortality. METHODS: This was a retrospective cross-sectional study of prescription patterns of antihyperglycemic medications claimed by individuals with type 2 diabetes (T2D) before and during the COVID-19 pandemic using the IQVIA Canada Longitudinal Prescription Claims database. The study period was from March 1, 2018, to February 28, 2021. The study outcomes are described on a monthly, quarterly, and yearly basis and overall, and by medication, medication class, and insurance coverage type. "New-to-molecule" patients were defined as those claiming a medication during the analysis period that they had no history of claiming in the database. Adults with at least 1 year of prescription history available and claiming their first prescription for an antihyperglycemic drug during the analysis period were classified as newly diagnosed with T2D. RESULTS: A similar number of people had at least 1 non-insulin antihyperglycemic prescription during the baseline, prepandemic, and pandemic periods in Canada (1,778,155, 1,822,403, and 1,797,272, respectively). However, the number of people initiating newer antihyperglycemic medications decreased at the beginning of the pandemic, in contrast to older medications, which remained consistent across the pandemic period. The number of people diagnosed with T2D decreased in the early months of the pandemic but recovered by October 2020. CONCLUSION: The COVID-19 epidemic in Canada impacted clinical care for at-risk Canadians, with fewer being prescribed newer antihyperglycemic drugs and a reduction in the number of diagnoses of T2D.

Use of the FreeStyle Libre system and diabetes treatment progression in T2DM: Results from a retrospective cohort study using a Canadian private payer claims database.

BACKGROUND: Up to one-third of Canadians are estimated to be living with prediabetes or diabetes. A retrospective study using Canadian private drug claims data was conducted to investigate whether flash glucose monitoring using the FreeStyle Libre system (FSL) among people with type 2 diabetes mellitus (T2DM) in Canada can be associated with changes in treatment intensification when compared with blood glucose monitoring (BGM) alone. MATERIALS AND METHODS: Using a Canadian national private drug claims database comprising approximately 50% coverage of insured individuals in Canada, cohorts of people with T2DM using FSL or BGM were identified algorithmically based on treatment history and followed over a 24-month study period, tracking their progression in diabetes treatment therapy. The Andersen-Gill model for recurrent time-to-event data was used to evaluate whether the rate of treatment progression differs between the FSL and BGM treatment cohorts. The survival function was used to calculate comparative treatment progression probabilities between the cohorts. RESULTS: In total, 373 871 people with T2DM met the inclusion criteria. Across treatment (FSL) and control (BGM) groups, people using FSL had a higher probability of treatment progression compared with BGM alone, with a relative risk ranging between 1.86 and 2.81 (p < .001). A higher probability of treatment progression was independent of the diabetes treatment at the enrolment date (index date) or the patient status, and independent of whether patients were treatment naïve or on established diabetes therapy. Assessment of the ending treatment relative to the starting therapy indicated that dynamic treatment changes were most evident for patients in the FSL cohort and that the FSL cohort had a much greater portion of patients who ended with insulin treatment (when they started with non-insulin treatment) compared with the BGM cohort. CONCLUSIONS: People with T2DM using FSL had a greater probability for treatment progression compared with BGM alone, irrespective of the starting therapy, which may suggest that FSL can be used to support escalation of diabetes therapy to improve therapeutic inertia in T2DM.

Impact of the COVID-19 Pandemic on Adults With Type 2 Diabetes Care and Clinical Parameters in a Primary Care Setting in Ontario, Canada: A Cross-sectional Study.

OBJECTIVES: Diabetes requires ongoing monitoring and care to prevent long-term adverse health outcomes. In Canada, quarantine restrictions were put into place to address the coronavirus-2019 (COVID-19) pandemic in March 2020. Primary care diabetes clinics limited their in-person services and were advised to manage type 2 diabetes (T2D) through virtual visits and reduce the frequency of routine diabetes-related lab tests and screening. METHODS: This retrospective cross-sectional study used de-identified patient records from a primary care electronic medical records database in Ontario, Canada, to identify people with T2D who had at least 1 health-care touchpoint between March 1, 2018, and February 28, 2021. Outcomes were described on a monthly or yearly basis: 1) number of people with primary care visits (in-person vs virtual); 2) number of people with referrals; 3) number of people with each of the vital/lab measures; and 4) results of the vital/lab measures. RESULTS: A total of 16,845 individuals with T2D were included. Compared with the pre-pandemic period, the COVID-19 period had a 16.8% reduction in the T2D population utilizing any primary care and an increase of 330.4% in the number of people with at least 1 virtual visit. Compared with the pre-pandemic period, fewer people had vital/lab measures in the pandemic period. However, among the people with the test results available, the average values for all tests were similar in the pre- and pandemic periods. CONCLUSION: Further research is needed to understand the impact of the reduction of in-person clinical care on the entire population with T2D.

Ease of Use of the iGlarLixi SoloStar Pen from the LixiLan ONE CAN Pen Sub-Study: Questionnaire Findings from People Living with Type 2 Diabetes and Their HealthCare Providers.

INTRODUCTION: For people with type 2 diabetes mellitus who do not achieve glycated hemoglobin A1C targets after treatment with basal insulin therapies, additional therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) may be required. One option is to use a once-daily fixed-ratio combination (FRC) of basal insulin and a GLP-1 RA such as iGlarLixi (which is composed of insulin glargine 100 U/ml and lixisenatide). However, the ease of transitioning from basal insulin to an FRC has not been studied. METHODS: This sub-study of the LixiLan ONE CAN trial (NCT03767543) was conducted to assess the ease of transitioning from insulin glargine 100 U/ml to the FRC, iGlarLixi, using the iGlarLixi SoloStar® pen. Patients completed a validated, ten-item questionnaire, and healthcare professionals (HCPs) completed a five-item questionnaire. Both questionnaires used either five-point Likert scales or yes/no answers as appropriate, and both were completed after 4 weeks of using the iGlarLixi SoloStar pen. RESULTS: Overall, 95.1% of patients reported that the iGlarLixi Solostar pen was "easy" or "very easy" to use. Similarly, 100% of HCPs reported that it was "easy" or "very easy" to train people to use the pen. Nearly all participants (97.5% of patients and 94% of HCPs) responded that they would recommend the iGlarLixi Solostar pen to others. CONCLUSIONS: These results suggest that during the transition from insulin glargine 100 U/ml to iGlarLixi, there were no difficulties associated with using the iGlarLixi SoloStar pen injector regarding instruction for use by HCPs or actual use by the majority of patients. The results indicate a broad consensus between patients and HCPs on the relative simplicity of transitioning from self-administration of insulin glargine 100 U/ml to iGlarLixi. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03767543; Date of registration: December 6, 2018; Retrospectively registered.

Many people take basal insulin to control their blood sugar, but for those in whom basal insulin injections do not work well enough to achieve their target blood glucose, treatment needs to be advanced. One option to do this is with a fixed-ratio combination therapy that combines basal insulin with a GLP-1 receptor agonist, such as iGlarLixi. Both basal insulin and fixed-ratio combination therapies are administered using injection pens, but the ease of transitioning from a basal insulin pen to a fixed-ratio combination pen has not been assessed. In this study, people with type 2 diabetes who had previously received the basal insulin insulin glargine 100 U/ml using a SoloStar^® pen, and who transitioned to the iGlarLixi SoloStar pen, were asked to complete a questionnaire to rate their experience of using the new pen injector after 4 weeks of use. Their doctors also completed a questionnaire at the same time. Over 95% of patients reported that the iGlarLixi SoloStar^® pen was "easy" or "very easy" to use, and all of the doctors reported that it was "easy" or "very easy" to train people to use it. Nearly all of those who completed questionnaires (97.5% of patients and 94% of doctors) said that they would recommend use of the iGlarLixi Solostar pen to others. These results suggest that both patients and their doctors thought that it was relatively easy to transition from self-administration of insulin glargine 100 U/ml to iGlarLixi using the SoloStar pen injector.