Premixed Insulin Research Articles

Glucose control after glucocorticoid administration in hospitalized patients \u2013 a retrospective analysis

BackgroundGlucocorticoid (GC)-induced hyperglycemia is a frequent adverse effect in hospitalized patients. Guidelines recommend insulin treatment to a target range of 6–10 mmol/L (108–180 mg/dl), but efficacies of particular regimes have not been well-studied.MethodsIn this retrospective cohort study, hospitalized patients receiving GCs at the medical ward were analyzed by treatment (basal-bolus vs. bolus-only vs. pre-mixed insulin) and compared to a non-insulin-therapy reference group. Coefficients of glucose variation (CV), percentage of glucose readings in range (4–10 mmol/L (72–180 mg/dl)) and hypoglycemia (< 4 mmol/L (< 72 mg/dl)) were evaluated.ResultsOf 2424 hospitalized patients receiving systemic GCs, 875 (36%) developed GC-induced hyperglycemia. 427 patients (17%) had a previous diagnosis of diabetes. Adjusted relative risk ratios (RRR) for the top tertile of CV (> 29%) were 1.47 (95% Cl 1.01–2.15) for bolus-only insulin, 4.77 (95% CI 2.67–8.51) for basal-bolus insulin, and 4.98 (95% CI 2.02–12.31) for premixed insulin, respectively.Adjusted RRR for percentages of glucose readings in range were 0.98 (95% Cl 0.97–0.99) for basal-bolus insulin, 0.99 (95% Cl 0.98–1.00) for premixed insulin, and 1.01 (95% Cl 1.00–1.01) for bolus-only insulin, respectively. Adjusted RRR for hypoglycemia was 13.17 (95% Cl 4.35–39.90) for basal-bolus insulin, 8.92 (95% Cl 2.60–30.63) for premixed insulin, and 2.99 (95% Cl 1.01–8.87) for bolus-only insulin, respectively.ConclusionsCurrent guidelines recommend a basal-bolus regimen for treatment of GC-induced hyperglycemia, but we found similar outcomes with pre-mixed and bolus-only insulin regimens. As GC-induced hyperglycemia is a frequent issue in hospitalized patients, it might be reasonable to prospectively study the ideal regimen.

IDegLira Improves Metabolic Control in Patients with Type 2 Diabetes Previously Treated with Premix Insulin.

Background:IDegLira( fixed combination of GLP 1 receptor agonist and insulin) has been shown to be effective in improving the glucoregulation in patients previously treated with oral therapy as well as individual components, GLP-1 receptor agonist or basal insulin.Objective:The aim of this study is to examine the parameters of metabolic control in patients treated with IDegLira who were previously treated with premix insulin in several daily doses and to compare them with patients whose premix insulin dose was increased.Methods:The study included 100 patients who had been previously treated with two or three daily doses of premix insulin. Half of the patients were switched to IdegLira( group I), and half (group II) had their insulin dose increased according to the clinical assessment of the physician. Fasting glucose, 2h postprandial glucose, HbA1c, BMI and insulin dose were determined at baseline and at follow-up after 6 months.Results:Patients treated with IDegLira compared to patients whose insulin dose was increased achieved significantly lower fasting glucose (p <0.001), postprandial glucose (p <0.001), HbA1c (p <0.001), BMI (p <0.001) with a significantly lower insulin dose (p <0.001). Comparison of the same parameters within the groups of patients at the beginning and after 6 months showed that patients who were switched from insulin premix to IDegLira achieved significantly lower fasting blood glucose (p <0.001), postprandial glucose (p <0.001), HbA1c (p < 0.001), BMI (p <0.001) with significantly lower insulin dose within the fixed combination (p <0.001). Patients with gradually increased insulin dose achieved significant reduction in fasting glucose (p = 0.021) and postprandial glucose (p = 0.036),but with a significantly higher insulin dose (p = 0.005). There was also a slight increase in BMI that was not statistically significant (p = 0.267).Conclusion:The obtained data suggest that switching patients from a complex insulin regimen to a fixed combination of basal insulin and GLP 1 receptor agonist in comparison to increases in insulin dose results in a significant improvement in fasting glucose, postprandial glucose, HbA1c, and BMI. The results were achieved with a significantly lower daily insulin dose.

Which Aspect of Patient-Provider Relationship Affects Acceptance and Adherence of Insulin Therapy in Type 2 Diabetes Mellitus? A Qualitative Study in Primary Care.

PurposeIn type 2 diabetes mellitus (T2DM), insulin therapy is often recommended to achieve the optimal control of disease, thereby preventing the onset and progression of diabetes-related complications. Despite knowing about the benefits, it has been reported that 71% of patients refuse insulin and the adherence rate ranges from 30 to 80%. Patient–provider relationship (PPR) may affect such insulin-related behaviours, but little is known about which aspect of PPR affects this. This study aimed to explore the key aspect of the patient–provider relationship that affects the initial insulin acceptance and continued adherence.Patients and MethodsWe used the grounded theory approach in this qualitative research. The study was conducted at two primary care clinics between September 2019 and January 2021. Patients with T2DM on basal or premixed insulin were recruited using maximum variation sampling. Data were collected using semi-structured in-depth interviews and transcribed verbatim for analysis using constant comparison and synthesis.ResultsTwenty-one participants with different levels of diabetes control and adherence were recruited. Four themes that emerged were 1) patient–provider interaction, 2) addressing the psychological fears, 3) gaining confidence in handling insulin equipment and 4) follow-up after insulin initiation. Among the subthemes, trust in doctors, provider’s communication skills, patient-centred decision-making and continuity of care positively influenced insulin acceptance and adherence. Conversely, fear of being judged by the provider hindered open communication around non-adherence. Various aspects of interaction with nurses helped in alleviating patient’s fear of injection and gaining confidence with the insulin equipment.ConclusionMany aspects of PPR affect insulin acceptance and adherence. Among these, gaining patients’ trust, effective patient–provider communication, patient-centred decision-making, and ensuring continuity of care improve both insulin acceptance and treatment adherence. Various interactions with nurses help in addressing fears surrounding injection and gaining acceptance towards insulin therapy. Patients’ fear of being blamed or judged by the provider negatively affects open communication around non-adherence.

Assessment of Insulin Therapy in 281 Children and Adolescents with Type 1 Diabetes in Senegal

Introduction: In Senegal, with the CDIC “Changing Diabetes In children” project, insulin has been made free. The objective of this study was to evaluate the accessibility and modalities of insulin therapy in the management of type 1 diabetes. Methodology: This was a retrospective study including patients followed for type 1 diabetes (T1DM) in hospital between April 2018 and December 2020. Results: 281 patients were included. The mean age was 14.22 years. The mean age at diagnosis was 11.28 years. Ketoacidosis was the main mode of discovery of diabetes at 51.6%. Premix and rapid insulins were most commonly used at 84.7% and 82.9% respectively, most often in combination. The most commonly used treatment regimen was three injections/day in 82.5% of cases. The average daily insulin dose was 0.62 IU/Kg/dr. Of the patients, 219 (78%) were self-monitoring of blood glucose. The average number of blood glucose checks was 1.78 per day. 76 patients (27%) went days without an insulin injection and up to 7 days in 51% of cases. The main reasons were forgetfulness, therapeutic errors and stock-outs. Hypoglycaemia was observed in 14.2%. The average glycated haemoglobin was 10%. Conclusion: Despite the efforts made, there are still challenges to improve access to insulin. The reinforcement of therapeutic education on insulin therapy is essential for a better quality of life of diabetic children and adolescents.

Pharmacokinetic Similarity between Biosimilar Insulin Aspart Premix SAR341402 Mix 70/30 and Originator Insulin Aspart Mix 70/30 (NovoMix 30) in Indian Adults with Type 2 Diabetes: GEMELLI M Substudy.

Background:We compared the pharmacokinetic exposure, efficacy, safety and immunogenicity of biosimilar insulin aspart premix SAR341402 Mix 70/30 (SARAsp-Mix) with its originator NovoMix® 30 insulin aspart mix (NN-Mix) in adults with type 2 diabetes.Methods:This was a randomized, open-label, parallel-group, substudy of the phase 3 GEMELLI M trial performed in three Indian centres. Totally 13 Indian participants previously treated with premix insulin received a single subcutaneous 0.3 U/kg dose of each treatment and underwent pharmacokinetic sampling for 16 h after dosing. Participants were then treated for 26 weeks as per the main GEMELLI M trial with efficacy, safety and immunogenicity compared between groups.Results:The extent of exposure (area under the plasma concentration-time curve and maximum insulin aspart concentration) to SAR341402 insulin aspart in SARAsp-Mix and to insulin aspart in NN-Mix was similar following single doses of the allocated treatment. After 26 weeks, the mean ± SD [median] change in HbA1c from baseline was similar in both treatment groups (SARAsp-Mix −0.38% ± 1.54 [−1.00%]; NN-Mix −0.18% ± 1.97 [−0.80%]). Other efficacy endpoints, insulin dosages, anti-insulin aspart antibody response, hypoglycemia and adverse events were similar between groups.Conclusions:Our results support the findings from previous studies, that SARAsp-Mix has a similar pharmacokinetic profile to NN-Mix and provides effective glycemic control with similar safety and immunogenicity profile in Indian adults with type 2 diabetes.

Pre-mixed insulin has a similar efficacy to basal-bolus insulin in reducing HbA1c levels in type 2 diabetics

A clinical decision report using: Fulcher G, Roberts A, Sinha A, Proietto J. What happens when patients require intensification from basal insulin? A retrospective audit of clinical practice for the treatment of type 2 diabetes from four Australian centres. Diabetes Research and Clinical Practice, 2015;108(3):405–413. https://doi.org/10.1016/j.diabres.2015.03.004 for a patient with uncontrolled type 2 diabetes.

Efficacy and Safety of Insulin Degludec/Insulin Aspart Compared with a Conventional Premixed Insulin or Basal Insulin: A Meta-Analysis.

Insulin degludec/insulin aspart (IDegAsp) is a novel co-formulation of 70% insulin degludec and 30% insulin aspart. The present meta-analysis was conducted to assess the efficacy and safety of IDegAsp compared with a conventional premixed insulin or basal insulin. We extracted data from citation databases, including PubMed, EMBASE, and the Cochrane Library, since inception to 2021. We calculated the mean differences for hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), self-measured mean glucose, and postprandial glucose (PPG) and odds ratios for confirmed hypoglycemia events. Compared with twice-daily conventional premixed insulin, twice-daily IDegAsp showed a similar effect on changes in HbA1c, but it significantly reduced FPG and self-measured mean glucose levels. Furthermore, compared to once-daily basal insulin, once-daily IDegAsp had a similar effect on changes in HbA1c, but it significantly reduced self-measured mean glucose and PPG levels. The risk of overall confirmed hypoglycemia was similar between treatments; however, the risk of nocturnal hypoglycemia events was significantly lower with IDegAsp than with conventional premixed insulin and basal insulin. Thus, IDegAsp was more effective than conventional premixed insulin and basal insulin at reducing blood glucose with fewer nocturnal hypoglycemia events.

The effect of insulin on post-exercise hypoglycemia in adults with type 2 diabetes participating in outpatient exercise-based cardiac rehabilitation.

Few studies have reported on self-monitored blood glucose changes following acute exercise, particularly in patients with type 2 diabetes prescribed oral sulfonylureas and insulin medication. This study sought to determine the magnitude of post-exercise blood glucose changes and incidence of hypoglycemia (blood glucose < 4.0mmol/L) in relation to medication regimen. A retrospective chart review was conducted in adults with type 2 diabetes attending a 6-month rehabilitation program. Demographics, medications, exercise prescription and patient-reported pre/post-BG values were collected at program initiation. It was hypothesized that patients with type 2 diabetes will experience a post-exercise capillary blood glucose reduction (ΔcapBG), and that incidents of hypoglycemia (< 4.0mmol/L) will be strongly associated with insulin or oral secretagogue class of medication. A chart review was conducted (n = 52, 46.2% males, mean age: 62.7 ± 8.3years, A1c: 7.7 ± 1.6%, body mass index, BMI: 34.4 ± 7.8kg/m2) in patients with type 2 diabetes (9.0 ± 7.7years since diagnosis). A greater reduction in BG was related to a greater pre-exercise BG (beta [95% CI]: -0.46 [-0.54, -0.37] mmol, p < 0.0001), independent of BMI and exercise duration. Post-exercise hypoglycemia (< 4.0mmol) was associated with prescribed insulin use (vs. non-users: 14.5% vs. 3.0%, p < 0.05). Among insulin users, pre-mixed insulin had the highest incidence of hypoglycemia (vs. non-users: 50% vs. 3%, p < 0.0001) and insulin (bolus and basal; vs. non-users: 11.1% vs. 3%, p = 0.04). These findings may suggest a low post-exercise hypoglycemia occurrence in patients with type 2 diabetes, except when taking insulin. Self-management strategies should be considered, especially for patients on insulin medications.

Availability, affordability and price components of insulin products in different-level hospital pharmacies: Evidence from two cross-sectional surveys in Nanjing, China.

The essential medicine--insulin cannot be easily accessed and afforded in many countries. To help address this issue, we evaluated the availability, affordability and price of insulin products in Nanjing, eastern China. Two cross-sectional studies were conducted in 2016 and 2018. A total of 56 hospital pharmacies were sampled, using a simplified and adapted World Health Organization/Health Action International (WHO/HAI) methodology. Prices were expressed as Median Price Ratios (MPRs) to Australian Pharmaceutical Benefit Scheme (PBS) prices. In addition, we investigated the price components of seven selected insulin products as a case study before and after the Online Centralized Procurement Policy for Hospital Drugs in May, 2018. Affordability was presented as the number of daily wages of the lowest paid unskilled government worker (LPGW) required to purchase 1000IU of insulin based on the average courses of treatment, approximately 30 days' treatment. The availability of insulin products was very high in secondary hospitals and tertiary hospitals both in 2016 and 2018, but in community hospitals was very low. In 2018, the availability of prandial insulin products showed fluctuation compared to 2016. The availability of pre-mixed human insulin products was over 95% overall, and also very high (80%) in community hospitals in 2018. The prices of insulin products were much lower than PBS prices of Australian in this study, with the MPRs less than 1 (0.32 to 0.71 in 2016 vs. 0.30 to 0.68 in 2018) for all insulin types. But insulin products in Nanjing in 2016 and 2018 were considered unaffordable, because the number of daily wages of the LPGW needed to purchase for the 30 days treatment of insulin products ranged from 2.26 to 8.49 in 2016 and 1.88 to 7.09 in 2018. The manufacturers' selling price contributed the main part (74.15% to 77.70% before and 74.86% to 91.51% after the implementation of the bidding policy) of the price components of target insulin brands. The availability of insulin products was high in secondary hospitals and tertiary hospitals, but lower in community hospitals. However, the affordability in community hospitals was better than other hospitals, but the insulin products were still unaffordable for patients on low incomes. Further improvements of the availability accessibility and affordability of medicines in advancing health insurance policies and lowering drug prices should be put forward.

Advancing Therapy in Suboptimally Controlled Basal Insulin-Treated Type 2 Diabetes: Clinical Outcomes With iGlarLixi Versus Premix BIAsp 30 in the SoliMix Randomized Controlled Trial.

OBJECTIVETo directly compare the efficacy and safety of a fixed-ratio combination, of insulin glargine 100 units/mL and the glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi), with those of a premix insulin analog, biphasic aspart insulin 30 (30% insulin aspart and 70% insulin aspart protamine) (BIAsp 30) as treatment advancement in type 2 diabetes suboptimally controlled on basal insulin plus oral antihyperglycemic drugs (OADs).RESEARCH DESIGN AND METHODSIn SoliMix, a 26-week, open-label, multicenter study, adults with suboptimally controlled basal insulin–treated type 2 diabetes (HbA1c ≥7.5% and ≤10%) were randomized to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy end points were noninferiority in HbA1c reduction (margin 0.3%) or superiority in body weight change for iGlarLixi versus BIAsp 30.RESULTSBoth primary efficacy end points were met: after 26 weeks, baseline HbA1c (8.6%) was reduced by 1.3% with iGlarLixi and 1.1% with BIAsp 30, meeting noninferiority (least squares [LS] mean difference −0.2% [97.5% CI −0.4, −0.1]; P < 0.001). iGlarLixi was also superior to BIAsp 30 for body weight change (LS mean difference −1.9 kg [95% CI −2.3, −1.4]) and percentage of participants achieving HbA1c <7% without weight gain and HbA1c <7% without weight gain and without hypoglycemia (all P < 0.001). iGlarLixi was also superior versus BIAsp 30 for HbA1c reduction (P < 0.001). Incidence and rates of American Diabetes Association level 1 and 2 hypoglycemia were lower with iGlarLixi versus BIAsp 30.CONCLUSIONSOnce-daily iGlarLixi provided better glycemic control with weight benefit and less hypoglycemia than twice-daily premix BIAsp 30. iGlarLixi is a more efficacious, simpler, and well-tolerated alternative to premix BIAsp 30 in suboptimally controlled type 2 diabetes requiring treatment beyond basal insulin plus OAD therapy.Video 1 Overview of the SoliMix trial. Video available at https://bcove.video/3CcjXLkBrightcoveDefaultPlayer10.2337/62665211600016266521160001 Infographic available at https://care.diabetesjournals.org/content/dc21-0393-infographic

Trends in U.S. Insulin Use and Glucose Monitoring for People with Diabetes: 2009-2018.

The delivery and administration of insulin has undergone many changes over the years. This research examines U.S. trends in insulin use among people with type 1 diabetes (T1D) or type 2 diabetes (T2D) in the U.S. from 2009 to 2018. The IBM® MarketScan® Commercial and Medicare databases were used to identify trends in insulin use over 10 years. The study included people with T1D or T2D who filled a prescription for insulin in any calendar year from 2009 to 2018. The analyses examined insulin regimen and delivery and the use of glucose monitoring systems. Generalized estimating equations were used to test whether trends were statistically significant. Individuals with T1D were most commonly prescribed a basal and bolus insulin regimen or short/rapid insulin only, while for people with T2D the use of basal-only insulin increased significantly over the study period. In both groups there was a significant decline in the use of premix insulin from 2009 to 2018. Insulin pump use increased for individuals with T1D, while disposable pen use increased for people in both cohorts. In both cohorts, there was a statistically significant increase in the use of continuous glucose monitoring, although this increase was more pronounced and occurred earlier among individuals with T1D. Results indicate significant changes in insulin regimens and delivery and glucose monitoring from 2009 to 2018. These findings suggest that insulin prescribing continues to change in response to the development of new therapeutics, advances in insulin delivery technology, and glucose monitoring systems.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study

Aims To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). Methods Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. Results In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. Conclusions Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Clinical Benefit of Insulin Glargine 300 U/mL Among Patients with Type 2 Diabetes Mellitus Previously Uncontrolled on Basal or Premixed Insulin in Serbia: A Prospective, Observational, Single-Arm, Multicenter, Real-World Study.

IntroductionInsulin glargine 300 U/mL (Gla-300) is a novel glargine formulation which shows slower and more prolonged absorption following subcutaneous administration in comparison to insulin glargine 100 U/mL. In this prospective, observational, single-arm, multicenter, real-world study conducted in Serbia, we evaluated the effectiveness and safety of Gla-300 in patients with type 2 diabetes mellitus (T2DM) previously inadequately controlled with different basal or premix insulin therapy regimes.MethodsA total of 350 patients with T2DM were enrolled by 27 physicians, from date of the first patient in (12 December 2017) to the date of last patient completed/last patient out (30 October 2018), from both medical centers and general hospitals. Patients’ observation and data collection were performed at visit 1 (V1), i.e., the inclusion visit (3–6 months after Gla-300 introduction), including collection of retrospective data from the patients’ medical charts at the time of Gla-300 introduction, and at visit 2 (V2) (3–6 months after V1). The primary objective was to assess the change in glycated hemoglobin (HbA1c) level from day of the Gla-300 initiation to the end of the observational period, while the secondary objectives included other effectiveness, as well as safety and other clinically relevant data.ResultsThe mean age of the 350 patients was 63.4 ± 8.4 years and 56.3% were female. The mean duration of diabetes was 13.4 ± 7.4 years, while the mean duration of insulin therapy prior to Gla-300 initiation was 5.3 ± 3.9 years. There was a significant reduction in HbA1c level at each visit compared to the previous visit (8.63 ± 1.52% at baseline prior to Gla-300 initiation, 7.87 ± 1.13% at V1, 7.45 ± 1.05% at V2; p < 0.01 vs. previous visit) accompanied by significant reduction of all hypoglycemic events (p < 0.01).ConclusionInitiation of Gla-300 therapy significantly improved glycemic control and reduced the risk of hypoglycemia in patients with T2DM inadequately controlled with different basal or premix insulin therapy regimes.FundingSanofi Serbia.

748-P: Advancing Therapy in Uncontrolled Basal Insulin (BI)-Treated Type 2 Diabetes (T2D): Subanalysis of the SoliMix Trial in Participants in Europe

Introduction: Premix insulin is commonly used as an option for therapy advancement from BI in T2D, despite a greater risk of hypoglycemia and weight gain compared with BI. Methods: SoliMix, an open-label, multicenter, randomized study, compared once-daily iGlarLixi to twice-daily premix insulin analog (BiAsp 70/30) in adults with T2D and HbA1c ≥7.5-≤10 % on BI + oral antihyperglycemic drugs (OADs). Co-primary efficacy endpoints were non-inferiority in HbA­1c reduction or superiority in bodyweight change from baseline to Week 26 of iGlarLixi vs. BiAsp 70/30. This predefined subanalysis assesses SoliMix endpoints in participants who were in Europe at the time of the study (43% of total study population). Results: Both co-primary efficacy endpoints were met, as well as iGlarLixi superiority vs. BiAsp 70/30 in HbA1c reduction (Table). Significantly more iGlarLixi-treated participants reached HbA1c Conclusions: Similar to the entire SoliMix cohort, once-daily iGlarLixi is a more favorable alternative to twice-daily premix insulin analog in people in Europe with T2D not at HbA1c target on BI + OADs, providing better glucose control, weight benefit, and less hypoglycemia. Disclosure A. Y. Cheng: Advisory Panel; Self; Abbott, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Research Support; Self; Applied Therapeutics, The Medicine Company, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bausch Health, Canada, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi. M. Bonnemaire: Employee; Self; Sanofi. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. R. J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, Board Member; Self; Novo Nordisk Foundation, Research Support; Self; AstraZeneca. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. C. Trescoli: None. M. Haluzik: Advisory Panel; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk, Consultant; Self; Sanofi. J. Seufert: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi, Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Sanofi. A. Alvarez: Employee; Self; Sanofi. E. Souhami: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. P. Picard: None. Funding Sanofi (EudraCT 2017-003370-13)

607-P: Glycemic Metrics in Japanese Flash Glucose Monitoring Users by Diabetes Type and Therapy

Our aim was to assess differences in glycemic metrics according to diabetes type and therapy in Japan. An optional survey was conducted for users of FreeStyle LibreTM readers in Japan (Jun2020 - Oct2020). Survey responses were linked to glucose data from Jan2017 - Oct2020. Four groups (adults) were used: type 1 diabetes (T1), type 2 on intensive insulin (T2 MDI), T2 on basal or pre-mixed insulin (T2 non-MDI), and T2 not on insulin (T2 non-insulin). A total of 2,434 users in Japan were analyzed: 1,237 T1, 429 T2 MDI, 256 T2 non-MDI, and 512 T2 non-insulin. Glucose control for T2 MDI and T2 non-MDI groups was similar. Mean avg glucose for T1 was similar to T2 insulin users, but TIR was lower and TB70 was higher for T1. The non-insulin group had high engagement (mean 21 scans/day), but tested BG less than once/day prior to the sensor. These patients also largely pay for the device without reimbursement and have more recent diabetes diagnoses than other groups. These data show the variety of users of the FreeStyle Libre system in Japan. The non-insulin group's engagement through high average scan rates despite lack of consistent BG testing before using the sensor demonstrates that patients find value in easier monitoring. High scan rates in all groups indicate that scanning is not a barrier to glucose monitoring. The data selects those users who responded to the optional survey but is comparable to the overall glucose control of all users in Japan.View largeDownload slideView largeDownload slide DisclosureW. Ogawa: Advisory Panel; Self; Abbott Diabetes, Novo Nordisk Pharma Ltd., Research Support; Self; Eli Lilly Japan K. K., Nippon Boehringer Ingelheim Co. Ltd., Takeda Pharmaceutical Co., Speaker's Bureau; Self; Dainippon Sumitomo Pharm, Kowa Company, Ltd., MSD K. K., Novartis Pharma K. K., Ono Pharmaceutical Co., Ltd. T. Urakami: None. T. Kadowaki: Other Relationship; Self; Asahi Mutual Life Insurance Company, MSD Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Company Limited, Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly Japan K. K., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly Japan K. K., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd. K. Kao: Employee; Self; Abbott Diabetes. L. Brandner: Employee; Self; Abbott Diabetes. K. Shimizu: Employee; Self; Abbott Japan Co., Ltd. T. Dunn: Employee; Self; Abbott Diabetes.

234-OR: Advancing Therapy in Uncontrolled Basal Insulin-Treated Type 2 Diabetes (T2D): Better Clinical Outcomes with IGlarLixi vs. Premix 70/30 in the SoliMix Trial

Introduction: iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, offers an alternative treatment advancement option to premix insulin for uncontrolled basal insulin-treated T2D. SoliMix, an open-label, multicenter study, was the first to compare these two insulin coformulations.Methods: SoliMix randomized adults with T2D and HbA1c ≥7.5-≤10 % on basal insulin + oral antihyperglycemic drugs (OADs) to once-daily iGlarLixi or twice-daily premix insulin 70/30 analogue (BiAsp 70/30). Co-primary efficacy endpoints were non-inferiority in HbA­1c reduction or superiority in bodyweight change from baseline to Week 26 of iGlarLixi vs. BiAsp 70/30.Results: Both co-primary efficacy endpoints were met (Table), as well as iGlarLixi superiority vs. BiAsp 70/30 in HbA1c reduction. Significantly more participants reached HbA1c <7 % without weight gain, and HbA1c <7 % without weight gain and without hypoglycemia, in the iGlarLixi group than the BiAsp 70/30 arm. Incidence and rates of hypoglycemia (Level 1 or 2) were lower with iGlarLixi vs. BiAsp 70/30.Conclusions: Based on better glucose control with weight benefit and less hypoglycemia, once-daily iGlarLixi is a favorable alternative to twice-daily premix 70/30 for advancing therapy in people with T2D uncontrolled on basal insulin + OADs.View largeDownload slideView largeDownload slide DisclosureJ. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. N. Demil: Employee; Self; Sanofi. M. Bonnemaire: Employee; Self; Sanofi. R. J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, Board Member; Self; Novo Nordisk Foundation, Research Support; Self; AstraZeneca. R. Emral: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Sanofi. L. Sauque-reyna: None. V. Mohan: None. C. Trescoli: None. S. N. Al sifri: None. N. Lalic: None. A. Alvarez: Employee; Self; Sanofi. P. Picard: None.FundingSanofi (EudraCT 2017-003370-13)

749-P: Advancing Therapy in Uncontrolled Basal Insulin (BI)-Treated Type 2 Diabetes (T2D): Subanalysis of the SoliMix Trial Outside Europe

Introduction: In many regions outside Europe, premix insulin is commonly used to advance therapy from BI when HbA1c targets are not met in T2D, despite a greater risk of hypoglycemia and weight gain than with BI. Methods: SoliMix, an open-label, multicenter, randomized study, compared once-daily iGlarLixi to twice-daily premix insulin analog (BiAsp 70/30) in adults with T2D and HbA1c ≥7.5-≤10 % on BI + oral antihyperglycemic drugs (OADs). Co-primary endpoints were non-inferiority in HbA­1c reduction or superiority in bodyweight change from baseline to Week 26 of iGlarLixi vs. BiAsp 70/30. This predefined subanalysis assesses SoliMix endpoints in participants outside Europe at the time of the study (57% of the total study population). Results: Both co-primary endpoints were met, as well as iGlarLixi superiority vs. BiAsp 70/30 in HbA1c reduction (Table). Significantly more iGlarLixi-treated participants reached HbA1c Conclusions: Similar to the entire cohort of SoliMix, once-daily iGlarLixi is a more favorable option to twice-daily premix insulin analog in people outside Europe with T2D not at HbA1c target on BI + OADs, providing better glucose control with weight benefit and less hypoglycemia. Disclosure V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. P. Picard: None. E. Souhami: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. R. J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, Board Member; Self; Novo Nordisk Foundation, Research Support; Self; AstraZeneca. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. A. Y. Cheng: Advisory Panel; Self; Abbott, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Research Support; Self; Applied Therapeutics, The Medicine Company, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bausch Health, Canada, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi. R. Emral: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Sanofi. L. Sauque-reyna: None. V. Mohan: None. S. N. Al sifri: None. A. Alvarez: Employee; Self; Sanofi. K. Djaballah: Employee; Self; Sanofi. Funding Sanofi (EudraCT 2017-003370-13)

747-P: Improved Treatment Perceptions with IGlarLixi vs. Premix Insulin in Type 2 Diabetes (T2D) Uncontrolled on Basal Insulin (BI) + Oral Antihyperglycemic Drugs (OADs): Patient-Reported Outcomes (PROs) of the SoliMix Trial

Introduction: Treatment complexity can impact treatment adherence, which may affect clinical outcomes in people with T2D. This analysis assessed PROs in the SoliMix trial.Methods: SoliMix, an open-label, multicenter study, randomized adults with T2D and HbA1c ≥7.5-≤10 % on BI + OADs to once-daily iGlarLixi or twice-daily premix insulin analog (BiAsp 70/30). Between-treatment differences from baseline to Week 26 (W26) in Treatment-Related Impact Measure for Diabetes (TRIM-D) scores are shown overall and by domain. Global Treatment Effectiveness Evaluation (GTEE) endpoints were analyzed descriptively at W26.Results: As well as providing better glycemic control, iGlarLixi demonstrated greater improvement in each TRIM-D domain vs. BiAsp 70/30 from baseline to W26 (Figure), with the greatest differences seen in diabetes management and treatment burden scores. GTEE scores also showed a greater proportion of participants and physicians who rated complete or marked improvement of diabetes control with iGlarLixi (81% and 83%) vs. BiAsp 70/30 (63% and 65%) at W26.Conclusions: Advancing BI with iGlarLixi resulted in a greater positive impact than with premix 70/30 for people with T2D uncontrolled on BI + OADs, suggesting a potentially lower treatment burden with iGlarLixi.View largeDownload slideView largeDownload slide DisclosureW. H. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Inc., Consultant; Self; Abbott Diabetes, ADOCIA, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Insulet Corporation, Lilly Diabetes, Novo Nordisk, Onduo LLC., Sanofi US. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. R. J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, Board Member; Self; Novo Nordisk Foundation, Research Support; Self; AstraZeneca. K. H. Whitmire: None. F. Giorgino: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Lilly Diabetes, Roche Diabetes Care. J. Chen: None. C. Nicholls: Employee; Self; Sanofi. E. Lew: Employee; Self; Sanofi. A. Alvarez: Employee; Self; Sanofi. M. Coudert: Employee; Self; Sanofi.FundingSanofi (EudraCT 2017-003370-13)

1-LB: Advancing Therapy in Basal Insulin Users with Type 2 Diabetes (T2D): Hypoglycemia as a Function of HbA1c in the SoliMix Trial

Introduction: Therapeutic approaches to advancing treatment from basal insulin in T2D require assessment of the benefits and risks of any chosen intervention. Methods: SoliMix was a 26-week, open-label, multicenter study in which adults (N=887) with T2D and HbA1c ≥7.5-≤10.0 % (≥58-≤86 mmol/mol) using basal insulin + metformin ± sodium-glucose co-transporter-2 inhibitors were randomized to once-daily iGlarLixi (fixed-ratio combination of basal insulin glargine 100 U/mL + lixisenatide) or twice-daily premix insulin 30/70 analog (BiAsp 30). HbA1c improved and bodyweight changes were favorable with iGlarLixi vs. BiAsp 30 (primary outcomes), while hypoglycemia event rates were also lower with iGlarLixi vs. BiAsp 30. This subanalysis assessed estimated hypoglycemia event rates over the whole treatment period as a function of HbA1c at Week 26. Results: Modelled event profiles for clinically significant hypoglycemia (ADA Level 2 [ Conclusion: Lower rates of hypoglycemia with iGlarLixi across a broad range of HbA1c suggests that iGlarLixi facilitates greater HbA1c improvement vs. premix insulin 30/70. Disclosure R. J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, Board Member; Self; Novo Nordisk Foundation, Research Support; Self; AstraZeneca. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. P. Home: Consultant; Self; American Diabetes Association, Kriya Technologies, Sanofi, Other Relationship; Self; Association of British Clinical Diabetologists, AstraZeneca, Novartis Malaysia, Sanofi, Research Support; Self; Sanofi. A. Y. Cheng: Advisory Panel; Self; Abbott, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Research Support; Self; Applied Therapeutics, The Medicine Company, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bausch Health, Canada, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi. F. Giorgino: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Lilly Diabetes, Roche Diabetes Care. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. E. Souhami: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. A. Alvarez: Employee; Self; Sanofi. A. H. Boss: Employee; Self; Sanofi, Stock/Shareholder; Self; Novo Nordisk A/S. L. Melas-melt: None. Funding Sanofi

746-P: Advancing Therapy in Uncontrolled Basal Insulin-Treated Type 2 Diabetes (T2D): Nocturnal Hypoglycemia in the SoliMix Trial

Introduction: Advancing treatment from basal insulin (BI) to premix insulin may improve glycemic control, though at the expense of greater hypoglycemia risk, including nocturnal hypoglycemia.Methods: SoliMix was a 26-week open-label, multicenter, randomized trial comparing iGlarLixi vs. premix insulin analog (BiAsp 70/30) in adults with T2D and HbA1c ≥7.5-≤10 % on BI + oral antihyperglycemic drugs (OADs). Primary results showed that switching to once-daily iGlarLixi resulted in better glucose control vs. twice-daily BiAsp 70/30. This subanalysis assessed nocturnal hypoglycemia (defined as bedtime-waking or 00:00-06:00 h [any; any symptomatic; ADA Level 1, 2, 3]) during the 26-week study period.Results: Incidence and rates of ADA Level 2 and any symptomatic nocturnal hypoglycemia were lower with iGlarLixi vs. BiAsp 70/30 for both nocturnal time intervals (Table). Incidence and rates of any and Level 1 nocturnal hypoglycemia were lower with iGlarLixi vs. BiAsp 70/30 between 00:00 and 06:00. No nocturnal ADA Level 3 (severe) hypoglycemia occurred in either treatment arm.Conclusions: Switching to iGlarLixi resulted in better glucose control with less nocturnal (00:00-06:00) hypoglycemia vs. premix insulin analog. A reduction in ADA Level 2 and any symptomatic hypoglycemia was also observed for the more clinically relevant window of bedtime to waking.View largeDownload slideView largeDownload slide DisclosureR. J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, Board Member; Self; Novo Nordisk Foundation, Research Support; Self; AstraZeneca. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. A. Y. Cheng: Advisory Panel; Self; Abbott, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Research Support; Self; Applied Therapeutics, The Medicine Company, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bausch Health, Canada, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. R. Choza: None. T. Alessa: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi-Aventis, Research Support; Self; Servier Laboratories, Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi-Aventis, Servier Laboratories. A. Alvarez: Employee; Self; Sanofi. E. Souhami: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. A. H. Boss: Employee; Self; Sanofi, Stock/Shareholder; Self; Novo Nordisk A/S. P. Picard: None.FundingSanofi (EudraCT 2017-003370-13)