Switching to tirzepatide 5 mg from GLP-1 RAs: Clinical expectations in the first 12 weeks of treatment.

OBJECTIVE: This prospective study aimed to describe the clinical course in terms of glycemic outcomes, body weight, and adverse events during the first 12 weeks following a switch from GLP-1 RAs directly to tirzepatide 5 mg. METHODS: Participants were ≥18 years with type 2 diabetes (T2D), HbA1c ≥6.5% to ≤9.0%, body mass index (BMI) ≥25 kg/m2 and were on a stable treatment dose of GLP-1 RAs (liraglutide once-daily (QD) [1.2, 1.8 mg], semaglutide once-weekly (QW) [0.5, 1.0, 2.0 mg], or dulaglutide QW [0.75, 1.5, 3.0, 4.5 mg]) for ≥3 months at baseline. The primary endpoint was HbA1c change from baseline at Week 12. Secondary endpoints included change from baseline in fasting serum glucose (FSG), body weight, and glucose assessed by continuous glucose monitoring. Safety was also assessed. RESULTS: Participants were 58.3 years on average, with baseline HbA1c 7.39%, BMI 35.18 kg/m2, T2D duration around 12.4 years, and included 55% females. Dulaglutide (42%) and semaglutide (55%) were the most commonly used GLP-1 RAs at baseline with dulaglutide 1.5 mg and semaglutide 1.0 mg being the most common treatment doses. At Week 12, mean HbA1c changed from baseline by -0.43%, FSG by -7.83 mg/dL, and body weight by -2.15 kg (all p<0.001). Glycemic outcomes and body weight improved in participants in all baseline GLP-1 RA subgroups. Twenty participants (13.2%) developed gastrointestinal events. Three (2%) participants discontinued tirzepatide due to adverse events. There were no severe hypoglycemic events or deaths. CONCLUSION: In this prospective study, when people with T2D on stable GLP-1 RA treatment were switched directly to tirzepatide 5 mg, they experienced improved glycemic outcomes and additional weight reduction with an acceptable risk of adverse GI events over 12 weeks.

Multicenter Evaluation of Ultra-Rapid Lispro (URLi) Insulin with Control-IQ Technology in Adults, Adolescents and Children with Type 1 Diabetes.

OBJECTIVE: To evaluate the safety and explore the efficacy of use of ultra-rapid lispro (URLi, Lyumjev) insulin in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology in children, teens and adults living with type 1 diabetes (T1D). METHODS: At 14 U.S. diabetes centers, youth and adults with T1D completed a 16-day lead-in period using lispro in a t:slim X2 insulin pump with Control-IQ 1.5 technology followed by a 13-week period in which URLi insulin was used in the pump. RESULTS: The trial included 179 individuals with type 1 diabetes (T1D) age 6 to 75 years. With URLi, 1.7% (3 participants) had a severe hypoglycemia event over 13 weeks attributed to override boluses or a missed meal. No DKA events occurred. Two participants stopped URLi use due to infusion site discomfort and one stopped after developing a rash. Mean time 70-180 mg/dL (TIR) increased from 65%±15% with lispro to 67%±13% with URLi (P=0.004). Mean insulin treatment satisfaction questionnaire (ITSQ) score improved from 75±13 at screening to 80±11 after 13 weeks of URLi use (mean difference = 6; 95% CI 4 to 8; P<0.001), with the greatest improvement reported for confidence avoiding symptoms of high blood sugar. Mean treatment related impact measure-diabetes (TRIM-D) score improved from 74±12 to 80±12 (P<0.001), and mean TRIM-Diabetes Device (TRIM-DD) score improved from 82±11 to 86±12 (P<0.001). CONCLUSIONS: URLi use in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology was safe for adult and pediatric participants with type 1 diabetes, with quality of life benefits of URLi use perceived by the study participants.

The Current and Future Role of Insulin Therapy in the Management of Type 2 Diabetes: A Narrative Review.

Early initiation of intensive insulin therapy has been demonstrated to be effective in controlling glycemia and possibly preserving beta-cell function. Innovations in insulin formulations and delivery systems continue. However, we have seen an acceleration in the development of new classes of diabetes medications for individuals with type 2 diabetes and obesity, such as, for example, glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These formulations have been shown to confer significant benefits in achieving good glycemic control with reduced hypoglycemia risk, weight loss, and cardiorenal protection. Therefore, it is reasonable to question whether there is still a role for insulin therapy in the management of type 2 diabetes. However, there are clear limitations inherent to GLP-1 RA therapy, including high rates of suboptimal adherence and treatment discontinuation due to high cost and side effects, which diminish long-term efficacy, and supply issues. In addition, newer formulations have shown improvements in convenience and tolerability, and have been shown to be even more effective when used in conjunction with basal insulin. In this narrative review, we discuss current evidence that supports GLP-1 RA use in combination with insulin therapy and the potential pitfalls of reliance on GLP-1 RAs as a substitute for insulin therapy.

Continuous Glucose Monitoring Metrics for Pregnancies Complicated by Diabetes: Critical Appraisal of Current Evidence.

Ascertaining the utility of continuous glucose monitoring (CGM) in pregnancy complicated by diabetes is a rapidly evolving area, as the prevalence of type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) escalates. The seminal randomized controlled trial (RCT) evaluating CGM use added to standard care in pregnancy in T1D demonstrated significant improvements in maternal glycemia and neonatal health outcomes. Current clinical guidance recommends targets for percentage time in range (TIR), time above range (TAR), and time below range (TBR) during pregnancy complicated by T1D that are widely used in clinical practice. However, the superiority of CGM over blood glucose monitoring (BGM) is still questioned in both T2D and GDM, and whether glucose targets should be different than in T1D is unknown. Questions requiring additional research include which CGM metrics are superior in predicting clinical outcomes, how should pregnancy-specific CGM targets be defined, whether CGM targets should differ according to gestational age, and if CGM metrics during pregnancy should be similar across all types of diabetes. Limiting the potential for CGM to improve pregnancy outcomes may be our inability to maintain TIR > 70% throughout gestation, a goal achieved in the minority of patients studied. Adverse pregnancy outcomes remain high in women with T1D and T2D in pregnancy despite CGM technology, and this review explores the potential reasons and questions yet to be investigated.

Real-World Evidence of Omnipod® 5 Automated Insulin Delivery System Use in 69,902 People with Type 1 Diabetes.

Background: The Omnipod® 5 Automated Insulin Delivery System was associated with favorable glycemic outcomes for people with type 1 diabetes (T1D) in two pivotal clinical trials. Real-world evidence is needed to explore effectiveness in nonstudy conditions. Methods: A retrospective analysis of the United States Omnipod 5 System users (aged ≥2 years) with T1D and sufficient data (≥90 days of data; ≥75% of days with ≥220 continuous glucose monitor readings/day) available in Insulet Corporation's device and person-reported datasets as of July 2023 was performed. Target glucose setting usage (i.e., 110-150 mg/dL in 10 mg/dL increments) was summarized and glycemic outcomes were examined. Subgroup analyses of those using the lowest average glucose target (110 mg/dL) and stratification by baseline characteristics (e.g., age, prior therapy, health insurance coverage) were conducted. Results: In total, 69,902 users were included. Multiple and higher glucose targets were more commonly used in younger age groups. Median percentage of time in range (TIR; 70-180 mg/dL) was 68.8%, 61.3%, and 53.6% for users with average glucose targets of 110, 120, and 130-150 mg/dL, respectively, with minimal time <70 mg/dL (all median <1.13%). Among those with an average glucose target of 110 mg/dL (n = 37,640), median TIR was 65.0% in children and adolescents (2-17 years) and 69.9% in adults (≥18 years). Subgroup analyses of users transitioning from Omnipod DASH or multiple daily injections and of Medicaid/Medicare users demonstrated favorable glycemic outcomes among these groups. Conclusion: These glycemic outcomes from a large and diverse sample of nearly 70,000 children and adults demonstrate effective use of the Omnipod 5 System under real-world conditions.

Peak insulin drip rate associated with decreased infections post-solid organ transplant.

Infection and rejection outcomes were retrospectively analyzed in patients following liver transplant and separately following heart transplant with patients being stratified by their severity of immediate postoperative insulin resistance as measured by the peak insulin drip rate that was required to reduce glucose levels. For each group, these peak insulin drip rates were divided into quartiles (Q). In liver transplant patients (n = 207), those in Q4 (highest infusion rate) had significantly fewer infections up to 6 months post-transplant (42.3% vs. 60.0%, p = .036) and borderline fewer rejection episodes (25.0% vs. 40.0%, p = .066) compared to Q1-Q3 patients. To confirm these unexpected results, a subsequent similar analysis in heart transplant (n = 188) patients again showed that Q4 patients had significantly fewer infections up to 6 months (19.1% vs. 53.9%, p < .0001) compared to Q1-Q3 patients. Logistic regression in a subset of 103 cardiac transplant patients showed that the maximum glucose during surgery, prior MI, and hypertension were associated with severe insulin resistance (SIR) status, while the presence of pre-existing diabetes and BMI were not. We hypothesize that patients are who are able to mount a more robust counter-regulatory response that causes the insulin resistance may be healthier and thus able to mount a better response to infections.

Two Years with a Tubeless Automated Insulin Delivery System: A Single-Arm Multicenter Trial in Children, Adolescents, and Adults with Type 1 Diabetes.

Background: The Omnipod® 5 Automated Insulin Delivery (AID) System was shown to be safe and effective following 3 months of use in people with type 1 diabetes (T1D); however, data on the durability of these results are limited. This study evaluated the long-term safety and effectiveness of Omnipod 5 use in people with T1D during up to 2 years of use. Materials and Methods: After a 3-month single-arm, multicenter, pivotal trial in children (6-13.9 years) and adolescents/adults (14-70 years), participants could continue system use in an extension phase. HbA1c was measured every 3 months for up to 15 months; continuous glucose monitor metrics were collected for up to 2 years. Results: Participants (N = 224) completed median (interquartile range) 22.3 (21.7, 22.7) months of AID. HbA1c was reduced in the pivotal trial from 7.7% ± 0.9% in children and 7.2% ± 0.9% in adolescents/adults to 7.0% ± 0.6% and 6.8% ± 0.7%, respectively, (P < 0.0001), and was maintained at 7.2% ± 0.7% and 6.9% ± 0.6% after 15 months (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 52.4% ± 15.6% in children and 63.6% ± 16.5% in adolescents/adults at baseline to 67.9% ± 8.0% and 73.8% ± 10.8%, respectively, during the pivotal trial (P < 0.0001) and was maintained at 65.9% ± 8.9% and 72.9% ± 11.3% during the extension (P < 0.0001 from baseline). One episode of diabetic ketoacidosis and seven episodes of severe hypoglycemia occurred during the extension. Children and adolescents/adults spent median 96.1% and 96.3% of time in Automated Mode, respectively. Conclusion: Our study supports that long-term use of the Omnipod 5 AID System can safely maintain improvements in glycemic outcomes for up to 2 years of use in people with T1D. Clinical Trials Registration Number: NCT04196140.

Comprehensive Telehealth Model to Support Diabetes Self-Management.

Importance: As the number of patients with diabetes continues to increase in the United States, novel approaches to clinical care access should be considered to meet the care needs for this population, including support for diabetes-related technology. Objective: To evaluate a virtual clinic to facilitate comprehensive diabetes care, support continuous glucose monitoring (CGM) integration into diabetes self-management, and provide behavioral health support for diabetes-related issues. Design, Setting, and Participants: This cohort study was a prospective, single-arm, remote study involving adult participants with type 1 or type 2 diabetes who were referred through community resources. The study was conducted virtually from August 24, 2020, to May 26, 2022; analysis was conducted at the clinical coordinating center. Intervention: Training and education led by a Certified Diabetes Care and Education Specialist for CGM use through a virtual endocrinology clinic structure, which included endocrinologists and behavioral health team members. Main Outcomes and Measures: Main outcomes included CGM-measured mean glucose level, coefficient of variation, and time in range (TIR) of 70 to 180 mg/dL, time with values greater than 180 mg/dL or 250 mg/dL, and time with values less than 70 mg/dL or 54 mg/dL. Hemoglobin A1c was measured at baseline and at 12 and 24 weeks. Results: Among the 234 participants, 160 had type 1 diabetes and 74 had type 2 diabetes. The mean (SD) age was 47 (14) years, 123 (53%) were female, and median diabetes duration was 20 years. Median (IQR) CGM use over 6 months was 96% (91%-98%) for participants with type 1 diabetes and 94% (85%-97%) for those with type 2 diabetes. Mean (SD) hemoglobin A1c (HbA1c) in those with type 1 diabetes decreased from 7.8% (1.6%) at baseline to 7.1% (1.0%) at 3 months and 7.1% (1.0%) at 6 months (mean change from baseline to 6 months, -0.6%, 95% CI, -0.8% to -0.5%; P < .001), with an 11% mean TIR increase over 6 months (95% CI, 9% to 14%; P < .001). Mean HbA1c in participants with type 2 diabetes decreased from 8.1% (1.7%) at baseline to 7.1% (1.0%) at 3 months and 7.1% (0.9%) at 6 months (mean change from baseline to 6 months, -1.0%; 95% CI, -1.4% to -0.7%; P < .001), with an 18% TIR increase over 6 months (95% CI, 13% to 24%; P < .001). In participants with type 1 diabetes, mean percentage of time with values less than 70 mg/dL and less than 54 mg/dL decreased over 6 months by 0.8% (95% CI, -1.2% to -0.4%; P = .001) and by 0.3% (95% CI, -0.5% to -0.2%, P < .001), respectively. In the type 2 diabetes group, hypoglycemia was rare (mean [SD] percentage of time <70 mg/dL, 0.5% [0.6%]; and <54 mg/dL, 0.07% [0.14%], over 6 months). Conclusions and Relevance: Results from this cohort study demonstrated clinical benefits associated with implementation of a comprehensive care model that included diabetes education. This model of care has potential to reach a large portion of patients with diabetes, facilitate diabetes technology adoption, and improve glucose control.

Integration of Continuous Glucose Monitoring Data into an Electronic Health Record System: Single-Center Implementation.

Managing data from continuous glucose monitoring (CGM) systems presents challenges to health care provider teams that rely on the electronic health record (EHR) during patient visits. A method of integrating CGM data with the EHR that relies on the Dexcom API was developed by Northwestern Medicine and Dexcom to address these challenges. Here, we describe the data management steps and user interface of the integrated system. Providers can access patients' historical and latest daily CGM data in the form of modal day plots and stacked columns showing time in various glucose concentration ranges. The integration facilitates the acquisition, storage, analysis, and display of CGM data within an EHR system and may be appropriate for deployment in other health care facilities.

Coverage for Continuous Glucose Monitoring for Individuals with Type 2 Diabetes Treated with Nonintensive Therapies: An Evidence-Based Approach to Policymaking.

Numerous studies have demonstrated the clinical benefits of continuous glucose monitoring (CGM) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) who are treated with intensive insulin regimens. Based on this evidence, CGM is now a standard of care for individuals within these diabetes populations and widely covered by commercial and public insurers. Moreover, recent clinical guidelines from the American Diabetes Association and American Association of Clinical Endocrinology now endorse CGM use in individuals treated with nonintensive insulin regimens. However, despite increasing evidence supporting CGM use for individuals treated with less-intensive insulin therapy or noninsulin medications, insurance coverage is limited or nonexistent. This narrative review reports key findings from recent randomized, observational, and retrospective studies investigating use of CGM in T2D individuals treated with basal insulin only and/or noninsulin therapies and presents an evidence-based rationale for expanding access to CGM within this population.

Beyond A1C: exploring continuous glucose monitoring metrics in managing diabetes.

Hemoglobin A1c (HbA1c) has long been considered a cornerstone of diabetes mellitus (DM) management, as both an indicator of average glycemia and a predictor of long-term complications among people with DM. However, HbA1c is subject to non-glycemic influences which confound interpretation and as a measure of average glycemia does not provide information regarding glucose trends or about the occurrence of hypoglycemia and/or hyperglycemia episodes. As such, solitary use of HbA1c, without accompanying glucose data, does not confer actionable information that can be harnessed to guide targeted therapy in many patients with DM. While conventional capillary blood glucose monitoring (BGM) sheds light on momentary glucose levels, in practical use the inherent infrequency of measurement precludes elucidation of glycemic trends or reliable detection of hypoglycemia or hyperglycemia episodes. In contrast, continuous glucose monitoring (CGM) data reveal glucose trends and potentially undetected hypo- and hyperglycemia patterns that can occur between discrete BGM measurements. The use of CGM has grown significantly over the past decades as an ever-expanding body of literature demonstrates a multitude of clinical benefits for people with DM. Continually improving CGM accuracy and ease of use have further fueled the widespread adoption of CGM. Furthermore, percent time in range correlates well with HbA1c, is accepted as a validated indicator of glycemia, and is associated with the risk of several DM complications. We explore the benefits and limitations of CGM use, the use of CGM in clinical practice, and the application of CGM to advanced diabetes technologies.

Use of Continuous Glucose Monitors to Manage Type 1 Diabetes Mellitus: Progress, Challenges, and Recommendations.

Type 1 diabetes (T1D) management has been revolutionized with the development and routine utilization of continuous glucose monitoring (CGM). CGM technology has allowed for the ability to track dynamic glycemic fluctuations and trends over time allowing for optimization of medical therapy and the prevention of dangerous hypoglycemic events. This review details currently-available real-time and intermittently-scanned CGM devices, clinical benefits, and challenges of CGM use, and current guidelines supporting its use in the clinical care of patients with T1D. We additionally describe future issues that will need to be addressed as CGM technology continues to evolve.

Improvements in Glycemic Outcomes in 4738 Children, Adolescents, and Adults with Type 1 Diabetes Initiating a Tubeless Insulin Management System.

INTRODUCTION: Despite recent advances in diabetes technology, most people living with type 1 diabetes mellitus (T1D) are unable to meet glycemic targets. Real-world evidence can provide insight into outcomes achieved with specific treatment devices when used in clinical practice. The aim of this study was to analyze real-world outcomes collected from a large cohort of people living with T1D and initiating treatment with the Omnipod DASH System. METHODS: In this retrospective observational study, real-world outcomes were analyzed from a database of information collected from people with T1D initiating the Omnipod DASH System. Information in the database was either taken directly from the patient's medical record or self-reported if medical records were unavailable. The primary outcome was change in glycated hemoglobin (HbA1c) from baseline (before initiation) to 3 months after initiation. Secondary outcomes were changes in total daily dose of insulin (TDD) and self-reported frequency of hypoglycemic events (< 70 mg/dL). Results are separated for the adult (≥ 18 years, N = 3341) and pediatric (< 18 years, N = 1397) cohorts. RESULTS: The change in HbA1c from baseline was - 0.9 ± 1.6% ( - 10 ± 18 mmol/mol; p < 0.0001) in adults and - 0.9 ± 2.0% ( - 10 ± 22 mmol/mol; p < 0.0001) in the pediatric cohort. For those previously using multiple daily injections, HbA1c decreased by - 1.0 ± 1.7% ( - 11 ± 19 mmol/mol) in adults and - 1.0 ± 2.1% ( - 11 ± 23 mmol/mol) in the pediatric cohort (both p < 0.0001). Hypoglycemic events decreased in adults from 2.9 to 1.3 episodes per week ( - 1.6 ± 3.2 events/week; p < 0.0001), and in the pediatric cohort from 2.8 to 1.5 episodes per week ( - 1.3 ± 2.7 events/week; p < 0.0001). In adults, TDD decreased by 19.9% (p < 0.0001), and it remained stable in the pediatric cohort (p > 0.05). CONCLUSIONS: Real-world outcomes from this large cohort of people initiating therapy with the Omnipod DASH System showed significant improvement in HbA1c and a substantial reduction in hypoglycemic events after 3 months of use.

11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2023.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.