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.

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.

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.

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.

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.

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.

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.

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.

Comparing a daily versus weekly titration algorithm in people with type 2 diabetes switching from basal insulin to iGlarLixi in the LixiLan ONE CAN randomized trial.

AIM: To compare the efficacy and safety of a simple daily titration algorithm compared with a weekly dose adjustment of iGlarLixi in people with type 2 diabetes. MATERIALS AND METHODS: LixiLan ONE CAN (NCT03767543), a randomized, 26-week, open-label, multicentre phase 3 trial conducted in Canada, involved 265 people with type 2 diabetes and an HbA1c of ≥7.5% to ≤ 10.5% or less (≥58 to ≤91 mmol/mol) on basal insulin for 6 months or longer. Participants were randomized 1:1 with instructions to self-titrate iGlarLixi daily (1 unit/day) or once weekly (2 or 4 units/week) to a common target fasting plasma glucose of 4.4 to 5.6 mmol/L (79 to 101 mg/dl). The primary objective was to show non-inferiority of the daily versus weekly titration algorithm. RESULTS: At 26 weeks, daily titration of iGlarLixi was not inferior to a weekly titration for both the prespecified primary endpoint of change in HbA1c from baseline (least square [LS] mean change: -1.24% vs. -0.92%, respectively; LS mean difference: 0.32%; 95% CI [0.07, 0.57]; P < .0001) and for the secondary endpoint of change in weight from baseline (LS mean change: -0.22 vs. +0.81 kg, respectively; LS mean difference: 1.03 kg; 95% CI [0.01, 2.06]; P < .0001). Indeed, for both the primary and secondary outcome, the daily titration of iGlarLixi was superior. There were no statistically significant differences in hypoglycaemia incidence between the two titration strategies during the 26-week study. CONCLUSION: A daily titration algorithm for switching basal insulin to iGlarLixi was shown to be non-inferior and superior for glycaemic control and weight compared with weekly titration.

Use of once-weekly semaglutide in patients with type 2 diabetes in routine clinical practice: Results from the SURE Canada multicentre, prospective, observational study.

AIM: To investigate once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) in routine clinical practice. METHODS: The SURE Canada study was a multicenter, prospective, observational study. Adults with T2D and one or more documented HbA1c values 12 weeks or less before semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~30 weeks). Secondary endpoints included change in body weight (BW), waist circumference and patient-reported outcomes (PROs) and the proportion of patients achieving HbA1c of less than 7.0%, weight loss (WL) of 5% or higher, and a composite of HbA1c reduction of 1% or higher and WL of 3% or higher at EOS. Data were analysed and presented for patients on semaglutide at EOS overall and for the following baseline medication subgroups: oral antihyperglycaemic drugs (OADs) only; GLP-1RA experienced; insulin ± OADs without GLP-1RA. RESULTS: In total, 452 patients initiated semaglutide and 356 completed the study on treatment. For the 452 patients, mean baseline HbA1c was 8.1%; 86 (19.0%) patients had HbA1c of less than 7.0%. Mean dose of semaglutide at EOS was 0.76 ± 0.31 mg. Mean HbA1c was reduced by 0.9%-point (95% confidence interval [CI]: 0.97; 0.78). Mean BW was reduced by 4.3 kg (95% CI: 4.79; 3.76). At EOS, 46.9% of patients achieved HbA1c of less than 7.0%, 40.9% achieved WL of 5% or higher and 24.1% achieved the composite endpoint. PROs improved from baseline to EOS. No new safety concerns were reported. CONCLUSIONS: In SURE Canada, patients treated with OW semaglutide in routine clinical practice experienced clinically significant improvements in HbA1c, BW and other outcomes, supporting semaglutide use in routine clinical practice.

Short-term intensive insulin as induction and maintenance therapy for the preservation of beta-cell function in early type 2 diabetes (RESET-IT Main): A 2-year randomized controlled trial.

AIM: To test the hypothesis that the addition of periodic courses of short-term intensive insulin therapy (IIT) could enhance the effect of metformin (MET) maintenance therapy on preservation of beta-cell function following induction IIT. METHODS: In this multicentre, randomized controlled trial, 108 adults with type 2 diabetes (median 1.3 years' duration; HbA1c 6.6% ± 0.6%) were randomized to 3 weeks of induction IIT (glargine, lispro) followed by MET maintenance, either with or without periodic 2-week courses of IIT every 3 months for 2 years. Beta-cell function was assessed by the Insulin Secretion Sensitivity Index-2 (ISSI-2) at an oral glucose tolerance test every 3 months. RESULTS: In both arms, induction IIT increased ISSI-2, improved whole-body insulin sensitivity and reduced hepatic insulin resistance (all P ≤ .0004). The primary outcome of baseline-adjusted ISSI-2 at 2 years was not improved by the addition of intermittent IIT (MET + IIT) and was slightly higher in the MET arm (baseline-adjusted difference -35 [95% CI: -66, -3]), with three additional beta-cell measures showing no significant differences. Baseline-adjusted HbA1c at 2 years did not differ between MET and MET + IIT (6.3% ± 0.1% vs. 6.4% ± 0.1%, P = .46), with 32.6% of participants in each arm maintaining HbA1c of 6.0% or less at 2 years. CONCLUSION: Although initial induction IIT induces metabolic improvement, subsequent repeat courses of IIT every 3 months do not further enhance the effect of MET maintenance therapy on beta-cell function.

Changes in adiposity mediate the associations of diet quality with insulin sensitivity and beta-cell function.

BACKGROUND AND AIMS: To examine the mediating role of adiposity on the associations of diet quality with longitudinal changes in insulin sensitivity and beta-cell function. METHODS AND RESULTS: Adults at-risk for type 2 diabetes (T2D) in the PROMISE cohort had 4 assessments over 9 years (n = 442). Alternate Healthy Eating Index (AHEI) scores were used to assess diet quality. Generalized Estimating Equations (GEE) evaluated the associations between the AHEI and longitudinal changes in insulin sensitivity (HOMA2-%S and ISI) and beta-cell function (IGI/HOMA-IR and ISSI-2). The proportion of the mediating effect of waist circumference changes was estimated using the difference method. In the primary longitudinal analysis, AHEI was positively associated with insulin sensitivity and beta-cell function over time (% difference per standard deviation increase of AHEI for HOMA2-%S (ß = 11.0, 95%CI 5.43-17.0), ISI (ß = 10.4, 95%CI 4.35-16.8), IGI/HOMA-IR (ß = 7.12, 95%CI 0.98-13.6) and ISSI-2 (ß = 4.38, 95%CI 1.05-7.80), all p < 0.05). There was no significant association between AHEI and dysglycemia incidence (OR = 0.95, 95%CI 0.77-1.17). Adjustments for longitudinal changes in waist circumference substantially attenuated all associations of AHEI with insulin sensitivity and beta-cell function. Mediation analysis indicated that waist circumference mediated 73%, 70%, 83% and 81% of the association between AHEI and HOMA2-%S, ISI, IGI/HOMA-IR, and ISSI-2, respectively (all p < 0.01). CONCLUSION: In a Canadian population at-risk for T2D, AHEI score was positively associated with changes in insulin sensitivity and beta-cell function. These associations were substantially mediated by waist circumference, suggesting that changes in adiposity may represent an important pathway linking diet quality with risk phenotypes for T2D.

Health Care Providers' Emotional Responses to Their Patients' Hypoglycemic Events: Qualitative Findings From the InHypo-DM Study, Canada.

OBJECTIVE: Hypoglycemia can cause psychological distress in people with diabetes; however, less is understood about the emotional impact of hypoglycemia on their health care providers (HCPs). This article focuses on the experiences and emotions of HCPs caring for patients with diabetes. METHODS: This was a descriptive qualitative study from the InHypo-DM research program. Purposive sampling was used to recruit 20 HCPs from a variety of professions for 30- to 45-minute semi-structured interviews. An iterative analysis was conducted to identify the overarching themes. RESULTS: Three overarching themes encompassed the responses of participants when their patients experienced hypoglycemia. The first was a sense of professional responsibility, as participants felt they must have failed or inadequately fulfilled their professional duties. The second was a more personal range of emotions such as sadness and guilt. The final theme was how these emotions created a "call to action," prompting participants to identify potential strategies to prevent future hypoglycemic events. CONCLUSION: This qualitative study highlights the emotional impact of patients' hypoglycemia on HCPs. Although it may have been expected that HCPs have a strong sense of professional responsibility, it was unexpected that these responses often became personal emotions. To ameliorate the negative impact of these responses on patient care, HCPs should engage in activities that enable them to anticipate and manage their own emotional responses. In addition, strategies to optimize hypoglycemia detection and prevention should be promoted.

The importance of the initial period of basal insulin titration in people with diabetes.

Achieving target glycaemic control is essential in people with diabetes to minimize the risk of long-term complications, and many people with type 2 diabetes will ultimately require basal insulin (BI) therapy to achieve their individualized glycaemic targets. Usually, the first 12 weeks following initiation of BI therapy represents the period when the greatest dose increases and glycaemic reductions occur. Effective glycaemic control combined with minimizing the risk of hypoglycaemia is important to enable the achievement of glycaemic control in the longer term. However, substantial therapeutic inertia exists in clinical practice, both in initiation and up-titration of BI, owing to patient-, physician- and healthcare system-related barriers, including fear of hypoglycaemia and the perception of a burdensome regimen. The more prolonged duration of action, reduced glycaemic variability and lower risk of hypoglycaemia seen with second-generation versus first-generation BI analogues may help alleviate patients' and physicians' concerns and facilitate titration. In turn, optimal BI titration and subsequent metabolic benefits may help improve therapy adherence and self-management. This review details the clinical implications of prompt titration of BI to achieve early glycaemic control, and the importance of minimizing hypoglycaemia risk within the initial titration period. Facilitation of patients' self-management of BI is also addressed.

Similar glycaemic control and less hypoglycaemia during active titration after insulin initiation with glargine 300 units/mL and degludec 100 units/mL: A subanalysis of the BRIGHT study.

AIM: To further investigate glycaemic control and hypoglycaemia in BRIGHT, focusing on the titration period. MATERIALS AND METHODS: BRIGHT was a multicentre, open-label, randomized, active-controlled, two-arm, parallel-group, 24-week study in insulin-naïve patients with uncontrolled type 2 diabetes initiated on glargine 300 U/mL (Gla-300) (N = 466) or degludec (IDeg-100) (N = 463). Predefined efficacy and safety outcomes were investigated during the initial 12-week titration period. In addition, patients' characteristics and clinical outcomes were assessed descriptively, stratified by confirmed (≤3.9 mmol/L) hypoglycaemia incidence during the initial titration period. RESULTS: At week 12, HbA1c was comparable between Gla-300 (7.32%) and IDeg-100 (7.23%), with similar least squares (LS) mean reductions from baseline (-1.37% and - 1.39%, respectively; LS mean difference of 0.02; 95% confidence interval: -0.08 to 0.12). Patients who experienced hypoglycaemia during the initial titration period had numerically greater HbA1c reductions by week 12 than patients who did not (-1.46% vs. -1.28%), and higher incidence of anytime (24 hours; 73.3% vs. 35.7%) and nocturnal (00:00-06:00 hours; 30.0% vs. 11.9%) hypoglycaemia between weeks 13-24. CONCLUSIONS: The use of Gla-300 resulted in similar glycaemic control as IDeg-100 during the initial 12-week titration period of the BRIGHT study, when less anytime (24 hours) hypoglycaemia with Gla-300 versus IDeg-100 has been reported. Experiencing hypoglycaemia shortly after initiating Gla-300 or IDeg-100 may be associated with hypoglycaemia incidence in the longer term, potentially impacting glycaemic management.

Therapeutic Inertia in People With Type 2 Diabetes in Primary Care: A Challenge That Just Won't Go Away.

Therapeutic inertia is a prevalent problem in people with type 2 diabetes in primary care and affects clinical outcomes. It arises from a complex interplay of patient-, clinician-, and health system-related factors. Ultimately, clinical practice guidelines have not made an impact on improving glycemic targets over the past decade. A more proactive approach, including focusing on optimal combination agents for early glycemic durability, may reduce therapeutic inertia and improve clinical outcomes.

Reporting of hypoglycaemia in clinical trials of basal insulins: A need for consensus.

Hypoglycaemia is a common side-effect of diabetes therapies, particularly insulin, and imposes a substantial burden on individuals and healthcare systems. Consequently, regulatory approval of newer basal insulin (BI) therapies has relied on demonstration of a balance between achievement of good glycaemic control and less hypoglycaemia. Randomized controlled trials (RCTs) are the gold standard for assessing efficacy and safety, including hypoglycaemia risk, of BIs and are invaluable for obtaining regulatory approval. However, their highly selected patient populations and their conditions lead to results that may not be representative of real-life situations. Real-world evidence (RWE) studies are more representative of clinical practice, but they also have limitations. As such, data both from RCTs and RWE studies provide a fuller picture of the hypoglycaemia risk with BI therapies. However, substantial differences exist in the way hypoglycaemia is reported across these studies, which confounds comparisons of hypoglycaemia frequency among different BIs. This problem is ongoing and persists in recent trials of second-generation BI analogues. Although they provide a lower risk of hypoglycaemia when compared with earlier BIs, they do not eliminate it. This review describes differences in the way hypoglycaemia is reported across RCTs and RWE studies of second-generation BI analogues and examines potential reasons for these differences. For studies of BIs, there is a need to standardize aspects of design, analysis and methods of reporting to better enable interpretation of the efficacy and safety of such insulins among studies; such aspects include length of follow-up, glycaemic targets, hypoglycaemia definitions and time intervals for determining nocturnal events.

Superior efficacy of insulin degludec/liraglutide versus insulin glargine U100 as add-on to sodium-glucose co-transporter-2 inhibitor therapy: A randomized clinical trial in people with uncontrolled type 2 diabetes.

AIM: To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine 100 units/mL (IGlar U100) as add-on to sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy. MATERIALS AND METHODS: In this 26-week, phase IIIb, open-label, parallel-group, treat-to-target trial, conducted at 74 sites in 11 countries, insulin-naïve people aged ≥18 years with glycated haemoglobin (HbA1c) 53-97 mmol/mol (7.0-11.0%), body mass index 20-40 kg/m2 and inadequately controlled type 2 diabetes (T2D) on SGLT2 inhibitor ± oral antidiabetic drugs were randomized 1:1 to once-daily IDegLira or IGlar U100, both as add-on to existing therapy. The primary endpoint was change in HbA1c from baseline to week 26. RESULTS: A total of 210 participants were randomized to each treatment arm. Mean HbA1c reductions were 21 mmol/mol (1.9%-points) with IDegLira and 18 mmol/mol (1.7%-points) with IGlar U100; confirming non-inferiority (P < 0.0001) and superiority of IDegLira (difference in HbA1c change -3.90 mmol/mol; 95% confidence interval [CI] -5.45; -2.35 (-0.36%-points; 95% CI -0.50, -0.21)). Superiority for IDegLira over IGlar U100 was also confirmed for: body weight (difference -1.92 kg; 95% CI -2.64, -1.19); severe or blood-glucose-confirmed symptomatic hypoglycaemia (rate ratio 0.42; 95% CI 0.23, 0.75); total daily insulin dose (difference -15.37 U; 95% CI -19.60, -11.13). The overall treatment-emergent adverse event rate was higher with IDegLira as a result of higher increased lipase and nausea rates. CONCLUSIONS: The favourable safety and efficacy profile of IDegLira in people with uncontrolled T2D on SGLT2 inhibitors, and lower weight gain and hypoglycaemia risk versus IGlar U100, suggest that clinicians should consider IDegLira initiation in this population.