Insulin Glargine in Type 1 Diabetes Mellitus: A Review of Clinical Trials and Real-world Evidence Across Two Decades.

BACKGROUND: Over the past two decades, insulin glargine 100 U/mL (Gla-100) has emerged as the "standard of care" basal insulin for the management of type 1 diabetes mellitus (T1DM). Both formulations, insulin glargine 100 U/mL (Gla-100) and glargine 300 U/mL (Gla- 300) have been extensively studied against various comparator basal insulins across various clinical and real-world studies. In this comprehensive article, we reviewed the evidence on both insulin glargine formulations in T1DM across clinical trials and real-world studies. METHODS: Evidence in T1DM for Gla-100 and Gla-300 since their approvals in 2000 and 2015, respectively, were reviewed. RESULTS: Gla-100 when compared to the second-generation basal insulins, Gla-300 and IDeg-100, demonstrated a comparable risk of overall hypoglycemia, but the risk of nocturnal hypoglycemia was higher with Gla-100. Additional benefits of Gla-300 over Gla-100 include a prolonged (>24- hours) duration of action, a more stable glucose-lowering profile, improved treatment satisfaction, and greater flexibility in the dose administration timing. CONCLUSION: Both glargine formulations are largely comparable to other basal insulins in terms of glucose-lowering properties in T1DM. Further, risk of hypoglycemia is lower with Gla-100 than Neutral Protamine Hagedorn but comparable to insulin detemir.

Evolving Scope of Clinical Empathy in the Current Era of Medical Practice.

Clinical empathy is one of the most essential tools of medical practice, and it is an act of correctly acknowledging the emotional state of another without experiencing that state oneself. Empathy comprises four components. Mounting evidence exists to support the use of clinical empathy as a tactic for effective health care. Resolving the multi-fold barriers of clinical empathy is important. Clinical empathy is very important in the current era, and a trust-based relationship in patient care is a way to optimal clinical outcomes that can be achieved through better communication and treatment-compliance plans between health care professionals and patients.

Real-World User and Clinician Perspective and Experience with MiniMed™ 780G Advanced Hybrid Closed Loop System.

INTRODUCTION: The advanced hybrid closed loop (AHCL) MiniMed™ 780G system changes basal insulin delivery every 5 min and auto bolus in response to sensor glucose values. We assessed the performance of the AHCL system in real-world settings for individuals with type 1 diabetes (T1DM) as well as user and clinician perspectives and satisfaction. METHODS: We held two peer group discussions: one having adults with T1DM/parents of children and adolescents with T1DM to understand their experiences with the AHCL system and another with healthcare providers (HCPs). Responses from the discussions were analyzed and categorized into themes by two independent researchers, with any inconsistencies resolved by consensus. We also analyzed data from the system uploaded to CareLink personal software. Glycemic outcomes, including time in range (TIR), time below range (TBR), time above range (TAR), mean sensor glucose (SG) levels, glucose management indicator (GMI), sensor use, and percentage of time spent in AHCL, were determined. RESULTS: The peer group discussions revealed numerous key themes and issues for each group, such as the significance of setting reasonable expectations, carbohydrate counting and bolus dosing, technical difficulties, and overall user experience. The users (n = 25; T1DM; 17 female; age 13.8 ± 7.49 years; A1C 6.54 ± 0.45%; duration of diabetes 6 ± 6.78 years) were very satisfied with the system. Most users experienced consistent blood glucose values with very few hypoglycemic episodes. However, there were a few limitations reported, such as hyperglycemic episodes caused by inaccuracies in carb counting, issues with sensor connectivity, and cannula blockages or kinking for those using insulin Fiasp. Users achieved a mean GMI of 6.4 ± 0.26%, TIR of 83.0 ± 8.12%, TBR (54-70 mg/dL) of 2.0 ± 0.81%, TBR* (< 54 mg/dL) of 0%. All of the users achieved a TIR of > 70%. CONCLUSION: The use of the AHCL system in T1DM resulted in robust glycemic control, minimizing hypoglycemia. Providing training to both users and HCPs can help them use the system effectively.

Intermittent Use of Continuous Glucose Monitoring: A New Paradigm in Treatment of Type 2 Diabetes.

OBJECTIVES: To suggest how continuous glucose monitoring (CGM) may be used intermittently in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: The use of CGM is largely in those with type 1 diabetes (T1D), in whom it makes sense to use CGM continuously as CGM provides a valuable tool to not only adjust their insulin doses but also to match it with their diet, physical activity, and other lifestyle modifications. In the case of T2D, however, especially for those not on insulin, the use of CGM may not be needed on a continuous basis. The use of CGM on an intermittent basis is rarely discussed in the literature. This article tries to provide clinical situations where CGM can be used intermittently. RESULTS: Intermittent use of CGM defined as the "use of CGM once in 2 or 3 months or a fixed frequency," and may be useful in several situations in those with T2D. We suggest the following indications for the intermittent use of CGM in T2D-newly diagnosed patients where treatment is being started, uncontrolled diabetes where treatment is being altered, starting intensive lifestyle modification, during infections, during preoperative control, in children and adolescents with T2D, as a motivational tool to improve behavioral modification, after metabolic surgery, and in patients on steroids, apart from other indications. CONCLUSION: Intermittent use of CGM in T2D can be useful in special situations and can also be cost saving particularly in resource-constrained regions of the world.

Reducing the Cost of Diabetes Care with Telemedicine, Smartphone, and Home Monitoring.

The effect of an increasing diabetes population has resulted in escalated costs and overburdened physicians. The increase in cost is not due to the disease per se, but because of its largely preventable complications. Patient-friendly technologies are proven to significantly reduce complications and thereby cost, but seldom practised. Telemedicine is increasingly being utilized in diabetology to improve access to health care, quality of care, and clinical/psychosocial outcomes in patients with diabetes (PWD). In PWD, patient-physician interactions are essential for improving health outcomes and preventing long-term complications. Smartphones are one of the basic modalities for telemedicine application. Mobile phone messaging applications, including text messaging and multimedia message service, could offer a convenient and cost-effective way to support desirable health behaviors. There are diabetes-related mobile apps mainly focusing on self-management of diabetes, lifestyle modification, and medication adherence motivation. With the widespread availability of high-speed Internet, remote monitoring has also become popular. Home monitoring of blood glucose and blood pressure, wearable devices, and continuous glucose monitoring also play a vital role in bringing down the long­term vascular complications of diabetes and thereby reduce the overall cost and improve the quality of life of patients. There are hundreds of tech platforms for diabetes management, of which only a few with proven efficacy and safety are recommended by physicians.

Human Digital Twin for Personalized Elderly Type 2 Diabetes Management.

Managing Elderly type 2 diabetes (E-T2D) is challenging due to geriatric conditions (e.g., co-morbidity, multiple drug intake, etc.), and personalization becomes paramount for precision medicine. This paper presents a human digital twin (HDT) framework to manage E-T2D that exploits various patient-specific data and builds a suite of models exploiting the data for prediction and management to personalize diabetes treatment in E-T2D patients. These models include mathematical and deep-learning ones that capture different patient aspects. Consequently, the HDT virtualizes the patient from different viewpoints using an HDT that mimics the patient and has interfaces to update the virtual models simultaneously from measurements. Using these models the HDT obtains deeper insights about the patient. Further, an adaptive patient model fusing this information and a learning-based model predictive control (LB-MPC) algorithm are proposed. The geriatric conditions are captured as model parameters and constraints while solving the LB-MPC to personalize the insulin infusion for E-T2D management. The HDT is deployed on and illustrated with 15 patients using clinical trials and simulations. Our results show that HDT helps improve the time-in-range from 3-75% to 86-97% and reduces insulin infusion by 14-29%.

Comparing the benefits of applying a vacuum assisted lancing device in reducing lancing pain, improving self-monitoring frequency and reducing HbA1c in people with diabetes.

BACKGROUND AND AIMS: For most people with diabetes (PwD), lancing fingertips for obtaining a blood sample is unavoidable during blood glucose monitoring (BGM). This study investigated the potential benefits of applying a vacuum over the penetration site immediately, before, during, and after lancing to determine if a vacuum would allow a less painful lancing process from fingertips and alternate sites, while still drawing sufficient blood, thereby allowing PwD to have a painless lancing experience and improving self-monitoring frequency. The cohort was encouraged to use a commercially available vacuum assisted lancing device. Change in pain perception, testing frequency, HbA1c, and future probability of VALD use were determined. METHODS: In a 24-week randomized open-label, interventional, cross-over trial, 110 PwD were recruited who used VALD and non-vacuum conventional lancing devices, for 12 weeks each. Percentage reduction in HbA1c, percentage BGM adherence, scores of pain perception, and probability of selecting VALD in the future were measured and compared. RESULTS: There was reduction in overall HbA1c values (mean ± SD), (from 9.01 ± 1.68% at baseline to 8.28 ± 1.66%) and individually in T1D (from 8.94 ± 1.77% to 8.25 ± 1.67%) and T2D (from 8.31 ± 1.17% to 8.59 ± 1.30) after using VALD for 12 weeks. Lower pain perception and high probability of using VALD over conventional devices were observed. CONCLUSION: The study highlights the benefits of applying a vacuum to the lance site which enhances the effectiveness in reducing and eliminating pain, improving self-monitoring frequency, and lowering HbA1c over non-vacuum conventional devices.

Gender-associated cardiometabolic risk profiles and health behaviors in patients with type 2 diabetes: a cross-sectional analysis of the Joint Asia Diabetes Evaluation (JADE) program.

Background: In Asia, diabetes-associated death due to cardiorenal diseases were 2-3 times higher in women than men which might be due to gender disparity in quality of care and health habits. Methods: Adults with type 2 diabetes (T2D) from 11 Asian countries/areas were assessed using the same protocol (2007-2015). We compared treatment target attainment (HbA1c < 7%, blood pressure [BP] < 130/80 mmHg, risk-based LDL-cholesterol, lack of central obesity [waist circumference <90 cm in men or <80 cm in women), use of cardiorenal-protective drugs (renin-angiotensin system [RAS] inhibitors, statins), and self-reported health habits including self-monitoring blood glucose (SMBG) by gender. Analyses were stratified by countries/areas, age of natural menopause (<50 vs. ≥50 years), and comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure, kidney impairment [eGFR < 60 mL/min/1.73 m2]). Findings: Among 106,376 patients (53.2% men; median (interquartile range) diabetes duration: 6.0 (2.0-12.0) years; mean ± SD HbA1c 8.0 ± 1.9%; 27% insulin-treated), women were older and less likely to receive college education than men (28.9% vs. 48.8%). Women were less likely to smoke/drink alcohol and were physically less active than men. Women had lower BP (<130/80 mmHg: 29.4% vs. 25.7%), less general obesity (54.8% vs. 57.8%) but more central obesity than men (77.5% vs. 57.3%). Women were less likely to have ASCVD (12.8% vs. 17.0%) or heart failure (1.3% vs. 2.3%), but more likely to have kidney impairment (22.3% vs. 17.6%) and any-site cancer than men (2.5% vs. 1.6%). In most countries/areas, more men attained HbA1c <7% and risk-based LDL-cholesterol level than women. After adjusting for potential confounders including countries and centres, men had 1.63 odds ratio (95% CI 1.51, 1.74) of attaining ≥3 treatment targets than women. Interpretation: Asian women with T2D had worse quality of care than men especially in middle-income countries/areas, calling for targeted implementation programs to close these care gaps. Sponsor: Asia Diabetes Foundation. Funding: Nil.

Clinical Evidence and Practice-Based Guidelines on the Utility of Basal Insulin Combined Oral Therapy (Metformin and Glimepiride) in the Current Era.

BACKGROUND AND AIM: Basal insulin combined oral therapy consisting of insulin and oral anti-diabetic drugs (OADs) is recommended for type 2 diabetes uncontrolled on OADs. There is a lack of clear evidence and recommendations on the combined use of basal insulin analogues to more than one OADs (glimepiride plus metformin) in effective control of glycemic parameters and its safety in terms of reduced hypoglycemic events, weight gain and cardiovascular risk. In this context, a group of clinical experts discussed the utility of basal insulin combined oral therapy with metformin and glimepiride in the current era. METHODS: The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists and diabetologists from India and Nepal. RESULTS: The panel thoroughly reviewed existing literature on the subject and proposed clinical evidence and practice-based guidelines. CONCLUSION: These current clinical practice guidelines highlight the efficacy and safety of basal insulin combination therapy with various available basal insulins including neutral protamine hagedorn, detemir, glargine and degludec in addition to metformin and glimepiride therapy.

Expert Consensus Recommendations on Time in Range for Monitoring Glucose Levels in People with Diabetes: An Indian Perspective.

Keeping up with the global scenario, diabetes prevalence is on rise in India. Inadequate glycemic control is a major cause of diabetes-related morbidity and mortality. The conventional standards of care (SOC) in diabetes, including self-monitoring of blood glucose and measurement of glycated hemoglobin, have supported achievement of glycemic control, yet there are a few limitations. With the use of current technologies and metrics, such as continuous glucose monitoring (CGM) and standardized CGM data reporting, the continuous real-time glucose levels can be measured, and importantly, the percentage of time above, below, and within the target glucose range can be calculated, which facilitates patient-centric care, a current goal in diabetes management. International consensus recommendations endorse the incorporation of CGM and CGM data reporting in SOC for diabetes management. The guidelines provide time in range (TIR) thresholds for different patient populations and different types of diabetes. However, extrapolation of these global guidelines does not aptly cover the Indian population, which has diverse diet, culture, and religious practices. In this context, a consensus meeting was held in India in 2021 with experts in the field of diabetes care. The purpose of the meeting was to develop consensus recommendations for TIR thresholds for different patient profiles in India. Those expert recommendations, together with an evidence-based review, are reported here. The aim of this agreement is to aid clinicians across India to routinely use CGM and CGM data reports for optimizing individualized diabetes care, by implementing clinical targets for TIR.

Empowering Patients with Type 1 Diabetes through a Multidisciplinary Team-assisted, Technology-Enabled Education Program.

BACKGROUND: Carbohydrate counting is a tool that helps patients with type 1 diabetes (T1D) to control their blood glucose. It calculates the bolus insulin dose needed from the total amount of carbohydrates consumed at each meal. However, carbohydrate counting can be quite challenging. The Diabetes Tele Management System® (DTMS®) is a telemedicine-based program that enables the patient to interact directly with a professionally trained, multidisciplinary team (MDT) of experts. This, along with technology-enabled education programs, could allow people with T1D to achieve glycemic control. METHODS: Fifty patients with T1D between 5 and 35 years with a diabetes duration of at least 6 months, baseline HbA1c of 7 or above, using SCII or MDI and willing to take part in the study were invited to participate in an MDT-assisted technology-enabled program and trained trimonthly on carbohydrate counting. The control group went on to perform carbohydrate counting independently and used technologies at their convenience. The test group additionally received continuous individual assistance from the MDT. RESULTS: The MDT-assisted patients had significantly decreased HbA1c, blood glucose levels, decreased episodes of hyperglycemia and hypoglycemia, and reported a more positive outlook on life. CONCLUSION: Carbohydrate counting remains a challenge for youth with T1D, and errors in counting can have a clinical impact. Our data suggested that the assistance from an MDT of experts was associated with improved carbohydrate counting, which led to improved glycemic control and reduced complications.

Addendum 1: Forum for Injection Technique and Therapy Expert Recommendations, India.

With the emerging complexities in chronic diseases and people's lifestyles, healthcare professionals (HCPs) need to update their methods to manage and educate patients with chronic lifestyle disorders, particularly diabetes. The insulin injection technique (IIT), along with various parameters, must also be updated with newer methods. Forum for Injection Technique and Therapy Expert Recommendations (FITTER), India, has updated its recommendations to cover newer ways of detecting hypoglycaemia and lipohypertrophy, preventing needlestick injuries (NSIs), discouraging the reuse of insulin needles and encouraging good disposal. FITTER, India, is also introducing recommendations to calculate insulin bolus dose. These updated recommendations will help HCPs better manage patients with diabetes and achieve improved outcomes.

SGLT2i as a First-line Antihyperglycemic in the Management of Type 2 Diabetes in the Context of Indians: A Systematic Review and Consensus.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been used for almost a decade and have proven to be effective not only in managing Type 2 diabetes (T2D), but their cardio and renal protective features make them very useful in managing patients with risk of multiple comorbidities. This systematic review was undertaken by the authors because there is no evidence currently available in India that has studied the suitability of SGLT2i as a first-line agent in patients newly diagnosed with T2D in India. MATERIALS AND METHODS: First, literature was searched to identify features that are considered important when deciding on a first-line agent for managing T2D. A total of 5 broad topics were identified-glycemic control, extra glycemic effects, antihyperglycemic combination therapy, safety, and cost-effectiveness. These domains had further subheadings, and a total of 16 domains were identified. Metformin is the drug of choice as a first-line agent in such situations and has been considered the gold standard for evaluating the effects of SGLT2i across these domains. A systematic literature review on each domain was conducted to compare SGLT2i with the gold standard in Indian patients newly diagnosed with T2D. Evidence was graded (levels of evidence (LoE)-A, B, and C), and recommendations (class of recommendation (CoR)-I, II, and III) were classified by the expert group as defined in the methodology. RESULTS: According to the systematic reviews conducted, 11 domains had Level A evidence, 2 domains (impact on lipids and gut microbiome) had Level B, and 3 domains had Level C (ß-cell function, renal protection, and glycemic variability) evidence. Based on evidence and expert opinion, the authors recommend SGLT2i as a first-line agent for managing newly diagnosed patients with T2D with a Class I recommendation for 13 domains and Class II for the remaining 3 (impact on lipids, gut microbiome, and ß-cell function). Although a poorer level of evidence (Level C) was available for the glycemic variability domain, the authors still reported this as Class I recommendations according to their expert opinion and consensus. CONCLUSION: This article advocates adopting SGLT2 inhibitors as the primary treatment choice for treating patients with newly diagnosed T2D in India.

Health care delivery model in India with relevance to diabetes care.

The Indian healthcare scenario presents a spectrum of contrasting landscapes. Socioeconomic factors, problems with medical infrastructure, insufficiency in the supply of medical requisites, economic disparities due to major differences in diabetes care delivery in the government and private sectors and difficulty in accessing quality health care facilities challenges effective diabetes care in India. The article gives insights into the practical solutions and the proposed White paper model to resolve major challenges faced by the Indian diabetes care sector for effective diabetes care delivered at Jothydev's Diabetes Educational Forum Global Diabetes Convention 2019.

Sodium-glucose Cotransporter-2 Inhibitors in Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with Type 2 Diabetes Mellitus: A Meta-analysis.

BACKGROUND: The available evidence was systematically reviewed to evaluate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) on cardiovascular (CV) and renal outcomes in people with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors (MRF), with or without heart failure (HF), and per estimated glomerular filtration rate (eGFR) rate at baseline. METHODS: We comprehensively searched three electronic databases to retrieve publications up to 30th November 2019, which were screened for inclusion. The data extracted for the outcomes according to baseline ASCVD, HF, and eGFR levels were meta-analyzed using fixed effects model. RESULTS: Of the 735 screened citations, 15 primary and secondary publications from five CV or renal outcome trials were included. SGLT2is reduced the risk of CV death or hospitalization for HF (HHF), HHF alone, and composite renal-specific outcome, irrespective of ASCVD and HF at baseline. The three-point major adverse cardiovascular events (3P-MACE) risk was reduced by 14% (p<0.001) in patients with ASCVD and by 10% (p = 0.018) in those without baseline HF compared with their counterparts. SGLT2is significantly reduced the risk of MACE (18%) in patients with mild kidney dysfunction (eGFR within the range of 60-<90 mL/min/1.73 m2 and <60 mL/min/1.73 m2 ). CONCLUSION: SGLT2is are effective for both secondary and primary prevention of composite CV outcomes, and secondary prevention of MACE. The upcoming evidence may strengthen the primary prevention benefits of SGLT2is.

Combined associations of family history and self-management with age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 countries.

BACKGROUND: Family history (FamH) of type 2 diabetes might indicate shared genotypes, environments, and/or behaviors. We hypothesize that FamH interacts with unhealthy behaviors to increase the risk of early onset of diabetes and poor cardiometabolic control. METHODS: In a cross-sectional analysis of the prospective Joint Asia Diabetes Evaluation Register including patients from 427 clinics in 11 Asian countries/regions in 2007-2021, we defined positive FamH as affected parents/siblings and self-management as (1) healthy lifestyles (balanced diet, non-use of alcohol and tobacco, regular physical activity) and (2) regular self-monitoring of blood glucose (SMBG). RESULTS: Among 86,931 patients with type 2 diabetes (mean±SD age: 56.6±11.6 years; age at diagnosis of diabetes: 49.8±10.5 years), the prevalence of FamH ranged from 39.1% to 85.3% in different areas with FamH affecting mother being most common (32.5%). The FamH group (n=51,705; 59.5%) was diagnosed 4.6 years earlier than the non-FamH group [mean (95% CI): 47.9 (47.8-48.0) vs. 52.5 (52.4-52.6), logrank p<0.001]. In the FamH group, patients with both parents affected had the earliest age at diagnosis [44.6 (44.5-44.8)], followed by affected single parent [47.7 (47.6-47.8)] and affected siblings only [51.5 (51.3-51.7), logrank p<0.001]. The FamH plus ≥2 healthy lifestyle group had similar age at diagnosis [48.2 (48.1-48.3)] as the non-FamH plus <2 healthy lifestyle group [50.1 (49.8-50.5)]. The FamH group with affected parents had higher odds of hyperglycemia, hypertension, and dyslipidemia than the FamH group with affected siblings, with the lowest odds in the non-FamH group. Self-management (healthy lifestyles plus SMBG) was associated with higher odds of attaining HbA1c<7%, blood pressure<130/80mmHg, and LDL-C<2.6 mmol/L especially in the FamH group (FamH×self-management, pinteraction=0.050-0.001). CONCLUSIONS: In Asia, FamH was common and associated with young age of diagnosis which might be delayed by healthy lifestyle while self management  was associated with better control of  cardiometabolic risk factors especially in those with FamH.

The role of oral semaglutide in managing type 2 diabetes in Indian clinical settings: Addressing the unmet needs.

AIMS: Despite their established benefits, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remain underutilized for type 2 diabetes mellitus (T2DM) management, which indicates that subcutaneous injection is an unfavorable mode of delivery from the patient's perspective. This review summarizes existing challenges related to medication adherence and the use of antihyperglycemia injectables, revisits the established safety and efficacy of oral semaglutide, and explores its features and considerations for use among the Indian T2DM population. METHODS: We performed a literature search using MEDLINE and the National Institutes of Health Clinical Trials Registry from July 1, 2016, to July 1, 2021, to identify publications on oral semaglutide approval, T2DM treatment guidelines, and clinical evidence for oral drug formulation. RESULTS: Oral semaglutide is the first oral GLP-1 RA approved for T2DM patients based on phase 3, randomized PIONEER trials. The multitargeted action of this drug offers glycemic control, weight control, and cardiovascular, renal, and additional benefits, including patient convenience and enhanced medication adherence. In addition to achieving glycemic control, the cost of semaglutide is reported to be lower than other GLP-1 RA in the West, thus potentially mitigating the economic burden that appears to be high among the Indian population. CONCLUSIONS: Currently, there is no data available on oral semaglutide in Indian clinical settings. However, significant improvements in glycemic control, cardiac and renal benefits, as well as weight loss across clinical trials should encourage clinicians to prioritize oral semaglutide over other antidiabetic agents.