Total Daily Insulin Research Articles

Phosphoinositide 3-Kinase Inhibitor-Induced Hyperglycemia

Background: Phosphoinositide 3-kinase inhibitors (PI3Ki) are a new class of medications used to treat HR positive, HER2 negative, PIK3CA mutated advanced or metastatic breast cancer. Inhibition of PI3K, a key enzyme in the insulin signaling pathway, leads to disruption of glucose metabolism and frequently hyperglycemia. Here we present a case of difficult to treat PI3Ki-induced hyperglycemia from alpelisib. Case: 78 yo woman with metastatic breast cancer and NASH cirrhosis was referred for new hyperglycemia after starting alpelisib. Baseline HbA1c was 6%. She was initially started on metformin and glipizide without any blood glucose (BG) improvement. After 6 days, alpelisib was held with BG recovery. Alpelisib was restarted 1 month later, again resulting in hyperglycemia. Dapagliflozin treatment quickly improved BG to <200 mg/dL, but she developed candida intertrigo so it was discontinued and insulin was started. She also began a ketogenic diet. After 2 weeks of insulin titration, she had stable BG <200 on 47u of insulin a day.Within days, she was admitted with encephalopathy and a UTI which improved with antibiotics and lactulose. Alpelisib, initially held, was restarted on day 2 resulting in worsening hyperglycemia. Inpatient BG ranges on alpelisib were: fasting 191–358, pre-lunch 260–383, pre-dinner 308–404, and bedtime 330–355, despite a rapid increase of basal-bolus insulin and initiation of metformin, pioglitazone, and a ketogenic diet. Total daily insulin needs went from 18u, to 124u by day 5 of alpelisib. Imaging revealed new bone and hepatic metastases. With difficult to control hyperglycemia and cancer progression, alpelisib was discontinued with rapid improvement of hyperglycemia. Discussion: Hyperglycemia is a common adverse and on target effect of PI3Ki use. PI3K inhibition leads to acute hyperglycemia within hours. The pancreas responds by increasing insulin release. Transient hyperglycemia can occur in all patients, but may become persistent with underlying insulin resistance, as seen in our patient. T2DM (with HbA1c >6.5%) and all T1DM patients were excluded in alpelisib trials yet diabetes is not a formal contraindication. Providers should be vigilant for this complication in patients with diabetes and prediabetes. It has been suggested that exogenous insulin and medications that increase endogenous insulin secretion may be counterproductive because they overcome PI3Ki-induced insulin signaling disruption and compromise anti-tumor effectiveness of PI3Ki. Thus, the preferred and most effective treatment may be an SGLT2i as was the case in our patient. Insulin sensitizers and a ketogenic diet can potentially also be effective. Increasing insulin may have limited efficacy as seen with our patient. Future studies are needed to determine the best way to manage PI3Ki-induced hyperglycemia and the effect of potential treatments on anti-tumor efficacy.

The Use of Omnipod® 5 Automated Insulin Delivery System in Adults With Type 2 Diabetes With Suboptimal Glycemic Management: From Injections to Closed-Loop Therapy

Advances in automated insulin delivery (AID), integrating continuous glucose monitoring (CGM), insulin pump therapy, and dynamic insulin modulation, have mostly centered on type 1 diabetes. Very little data exists to characterize the use of AID in adults with type 2 diabetes in the outpatient setting despite the significant burden of disease. The increasing adoption of diabetes technology by this heterogenous population suggests that clinical evaluation of AID in type 2 diabetes is necessary. In this study, we seek to enroll adults with type 2 diabetes, previously on either multiple daily injections (MDI) or basal insulin only (pump naïve), both CGM users and CGM naïve, with A1C > 8%, to start AID using the tubeless, on-body Omnipod 5 system with insulin pod and Dexcom G6 sensor. This system has the novel feature1 of customizable glucose targets from 110-150mg/dL, which is useful for gradual reduction of mean glucose levels in patients acclimated to hyperglycemic ranges. In addition, the system adapts to the persistent hyperglycemia commonly seen in type 2 diabetes by increasing insulin delivery with each pod change. This feasibility study will enroll a minimum of 24 participants, following them through a 2-week baseline assessment and then an 8-week period of Omnipod 5 use in Automated Mode, all via the outpatient setting.To date, 3 participants have enrolled and are currently using the system: age (mean±SD) 54±12y, weight 79.7±9.0kg, baseline A1C 9.3±0.2% (range 9.1–9.5%), and duration of diabetes 18.3±12.4y. Previous anti-hyperglycemic agents including metformin and GLP-1R agonists were continued.Participants have used Omnipod 5 in Automated Mode ranging from 26 to 53 days. In the preliminary analysis of Automated Mode use, mean glucose of 194±33 mg/dL was achieved, corresponding to a glucose management indicator (GMI) of 8.0±0.8%. Time in range, 70-180mg/dL, was 49.0±19.2%, time <70mg/dL was 0.2±0.2%, >180mg/dL was 50.8±19.4%, and ≥250mg/dL was 19.3±15.6%. Average total daily insulin use was 77.9±41.4 units/day. In the most recent 14 days of use, GMI was further decreased to 7.6±0.5%, and time in range further increased to 57.6±14.1%. There have been no serious adverse events, including severe hypoglycemia, reported in over 110 person-days of system use to date.At completion, this study will provide a novel evaluation of the safety and effectiveness of AID in adults with type 2 diabetes with suboptimal glycemic management, despite the concomitant use of adjuvant anti-hyperglycemic agents.Reference: 1. Forlenza et. al. First outpatient evaluation of a tubeless automated insulin delivery system with customizable glucose targets in children and adults with type 1 diabetes. Diabetes Technol Ther 2021.

Efficacy and Safety of Ertugliflozin in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease Using Insulin

Abstract Introduction: Ertugliflozin (ERTU), a sodium-glucose cotransporter 2 inhibitor, is approved as an adjunct to diet and exercise to improve glycemic control in patients (pts) with type 2 diabetes mellitus (T2DM). Aim: As part of the VERTIS CV trial (NCT01986881), the efficacy and safety of ERTU were assessed in pts with T2DM and established atherosclerotic cardiovascular disease (ASCVD) inadequately controlled by insulin. Methods: Pts were randomly assigned to placebo (PBO), ERTU 5 mg or 15 mg once daily. A pre-specified sub-study was conducted in pts on a stable dose of insulin ≥20 units/day (± metformin). The primary endpoint was HbA1c change from baseline at 18 weeks. Key secondary endpoints included proportion of patients achieving HbA1c &amp;lt;7%, fasting plasma glucose (FPG), body weight (BW), and systolic blood pressure (SBP). Changes from baseline at Week 18 for continuous efficacy endpoints were assessed using a constrained longitudinal data analysis model. HbA1c reduction was also assessed in subgroups based on baseline HbA1c, age, sex, race, ethnicity, and use of metformin. Results: Of 8246 pts randomized in VERTIS CV, 1065 pts (ERTU 5 mg: 348; ERTU 15 mg: 370; PBO: 347) with T2DM and ASCVD were included in the sub-study. Mean baseline characteristics were similar across treatment groups; age 64.8 years, T2DM duration 16.7 years, HbA1c 8.4%, and eGFR 73.7 mL/min/1.73 m2. At baseline, 40.6% of pts were on insulin alone, 59.4% were receiving insulin + metformin; median (range) insulin dose was 58.0 (20–350) units/day. At Week 18, least squares mean change (95% confidence interval) from baseline in HbA1c was significantly greater with ERTU 5 mg and 15 mg vs PBO. PBO-adjusted differences were −0.6% (−0.7, −0.4) and −0.7% (−0.8, −0.5), for ERTU 5 mg and 15 mg, respectively (P&amp;lt;0.001 for both). HbA1c reductions were greater with ERTU vs PBO for all subgroups including by use of metformin. At Week 18, 10.7%, 20.7%, and 21.1% of pts with PBO, ERTU 5 mg and 15 mg, respectively, achieved HbA1c &amp;lt;7.0%. ERTU 5 mg and 15 mg significantly reduced FPG, BW, SBP, and ERTU 15 mg led to a small reduction in total daily insulin dose. The overall incidence of adverse events and serious adverse events was similar across treatment groups. In women, the incidences of genital mycotic infections was higher with ERTU 5 mg (3.4%; P=0.05) and ERTU 15 mg (3.6%; P=0.04) vs PBO (0.0%). The incidences of urinary tract infections (3.2–4.1%), symptomatic hypoglycemia (26.4–28.5%), and severe hypoglycemia (3.5–5.1%) were similar across treatment groups. The incidences of hypovolemia were low (1.4–2.4%) and similar across treatment groups. Conclusion: ERTU added to insulin (± metformin) led to greater reductions from baseline in HbA1c, FPG, BW, and SBP, and a higher proportion of pts achieving HbA1c &amp;lt;7.0%, vs PBO at 18 weeks in pts with T2DM and ASCVD, without increasing the risk of hypoglycemia.

Longevity of the novel ConvaTec infusion set with Lantern technology.

Current insulin infusion sets are approved for only 2-3 days. The novel ConvaTec infusion set with Lantern technology is designed to extend infusion set wear time. The goal of this pilot study was to evaluate the duration of wear for this set. This was a pilot safety study in adults with type 1 diabetes using tethered insulin pumps. Participants inserted the set and wore it for 10 days or until failure. Among 24 participants, two were excluded. Forty-five per cent of the sets lasted 10 days. Median wear time was 9.1 (7.1, 10.0) days. Among 12 premature failures, six (50%) involved adhesive failures, four (33%) hyperglycaemia unresponsive to correction, one (8%) hyperglycaemia with ketones and one (8%) infection. Average CGM glucose per day of infusion set wear showed a statistically significant increase over time, while total daily insulin over the same period did not change. In this pilot study, the duration of wear for the novel infusion set exceeded previously reported commercial sets (P < .001). This extended wear technology may eventually allow for a combined glucose sensor and infusion set.

Comparison of two insulin injection methods on control of type 2 diabetes; is the new protocol effective or not?

Introduction: Type 2 diabetes is a progressive disease with a significant risk for developing late complications. Objectives: This study aimed to determine if the discharge NPH and regular insulin doses of conventional insulin therapy protocol in which optimal glycemic control can be achieved are similar to NPH and regular insulin doses at beginning of the insulin protocol or not. In other words, we aimed to compare two insulin injection methods on the control of type 2 diabetes. Patients and Methods: This cross-sectional study was performed on hospital records of type II diabetic patients admitted for insulin therapy with the conventional protocol from 2008-2013. Treatment was initiated with the following proportions; morning NPH: 44%, morning regular dosage: 22%, evening NPH dosage: 17% and evening regular dosage: 17%. Insulin doses of the discharge day in which optimal glycemic control has been achieved were recorded and based on their mean, a protocol was made. Finally, two groups were categorized. Group 1 consisted of patients whose discharge insulin dose was in the range of the mean data of the study (±2 IU/mL) and patients whose discharge insulin dose was in accordance with the conventional protocol (±2 IU/mL) participated in group 2. Results: At discharge day, the mean morning NPH dose was 34.2±6.69, morning regular: 23.8±6.36, evening NPH: 21.26±6.75 and evening regular: 20.74±5.51. The discharge insulin ratios of the conventional protocol were similar to that of the admission ratios in only 17.7% of the patients. Only 34.5% of the patients could include in the new protocol and 50% of them didn’t fit any protocol. Conclusion: It is suggested to inject one-third of the total daily insulin need as NPH in the morning and divide the remained two-thirds between morning regular, evening NPH and evening regular equally. This may decrease the length of hospital stay and decrease the time to reach the desired glycemic control.

Efficacy and safety of the fixed-ratio combination of insulin degludec and liraglutide by baseline glycated hemoglobin, body mass index and age in Japanese individuals with type2 diabetes: A subgroup analysis of two phaseIII trials.

Aims/IntroductionTo assess efficacy and safety of insulin degludec/liraglutide (IDegLira) in Japanese participants with type 2 diabetes across different baseline characteristics.Materials and MethodsData from two randomized controlled trials were used: DUAL I Japan (n = 819 insulin‐naïve participants) and DUAL II Japan (n = 210 insulin‐experienced participants). Outcomes were assessed according to baseline glycated hemoglobin ( HbA1c; <8.0%, ≥8.0–<9.0%, ≥9.0%), body mass index (<25, ≥25–<30, ≥30 kg/m2) and age (<65, ≥65 years).ResultsIn DUAL I Japan, reductions in HbA1c with IDegLira versus degludec and liraglutide were observed across all subgroups (treatment differences: −0.48% to −0.72% vs degludec, −0.29% to −0.73% vs liraglutide). Results were similar with IDegLira versus degludec in DUAL II Japan (treatment differences: −0.82% to −1.61%). Treatment‐by‐subgroup interactions were significant for IDegLira versus liraglutide for baseline HbA1c and age in DUAL I Japan, and for IDegLira versus degludec for baseline HbA1c in DUAL II Japan. In DUAL I Japan, IDegLira was associated with less weight gain than degludec in most subgroups. In DUAL II Japan, IDegLira was associated with a small mean weight loss (except for baseline HbA1c ≥9.0%) versus a small gain for degludec (except for age ≥65 years subgroup); treatment‐by‐subgroup interactions were not significant. Total daily insulin dose was lower with IDegLira versus degludec across all categories, except for age >65 years in DUAL II Japan.ConclusionsIDegLira reduced HbA1c in Japanese participants with type 2 diabetes across baseline HbA1c, body mass index and age categories, without unexpected safety issues.

Hybrid closed-loop glucose control with faster insulin aspart compared with standard insulin aspart in adults with type 1 diabetes: A double-blind, multicentre, multinational, randomized, crossover study.

To evaluate the use of hybrid closed-loop glucose control with faster-acting insulin aspart (Fiasp) in adults with type 1 diabetes (T1D). In a double-blind, multinational, randomized, crossover study, 25 adults with T1D using insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4% ± 0.8% [57 ± 8 mmol/mol]) underwent two 8-week periods of unrestricted living comparing hybrid closed-loop with Fiasp and hybrid closed-loop with standard insulin aspart in random order. During both interventions the CamAPS FX closed-loop system incorporating the Cambridge model predictive control algorithm was used. In an intention-to-treat analysis, the proportion of time sensor glucose was in the target range (3.9-10.0 mmol/L; primary endpoint) was not different between interventions (75% ± 8% vs. 75% ± 8% for hybrid closed-loop with Fiasp vs. hybrid closed-loop with standard insulin aspart; mean-adjusted difference -0.6% [95% CI -1.8% to 0.7%]; p < .001 for non-inferiority [non-inferiority margin 5%]). The proportion of time with sensor glucose less than 3.9 mmol/L (median [IQR] 2.4% [1.2%-3.2%] vs. 2.9% [1.7%-4.0%]; p = .01) and less than 3.0 mmol/L (median [IQR] 0.4% [0.2%-0.7%] vs. 0.7% [0.2%-0.9%]; p = .03) was reduced with Fiasp versus standard insulin aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. 8.0 ± 0.8 mmol/L; p = .13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; p = .90). Total daily insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; p = .45). No severe hypoglycaemia or ketoacidosis occurred. The use of Fiasp in the CamAPS FX closed-loop system may reduce hypoglycaemia without compromising glucose control compared with standard insulin aspart in adults with T1D.

Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses.

IntroductionThe efficacy and safety of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, were investigated in patients with type 2 diabetes (T2D) in the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) programme. The current post-hoc exploratory subgroup analyses evaluated outcomes by background medication and insulin regimen subgroups.MethodsData from patients in the PIONEER 3–5, 7 and 8 trials receiving once-daily oral semaglutide (14 mg/flexibly dosed) or a comparator (placebo, sitagliptin 100 mg or liraglutide 1.8 mg) were analysed for efficacy (glycated haemoglobin [HbA1c] and body weight changes from baseline to planned end of treatment) and safety outcomes. Patients were grouped according to background medication (metformin, sulphonylurea, thiazolidinedione, sodium-glucose cotransporter-2 inhibitor, insulin, or combinations thereof). Efficacy outcomes were analysed using the trial product estimand (which assumes that patients remained on the trial product without rescue medication use). A separate analysis by background insulin regimen (basal, premixed or basal-bolus) was done for PIONEER 8 using the treatment policy estimand (regardless of trial product discontinuation or rescue medication use). Safety outcomes were analysed descriptively for all patients.ResultsIn total, 2836 patients receiving oral semaglutide 14 mg/flexibly dosed or comparators were included. Baseline characteristics were generally similar across background medication subgroups within each trial. Diabetes duration tended to be longer in patients receiving more background medications. Greater HbA1c and body weight reductions were seen across background medication subgroups with oral semaglutide (changes from baseline: − 1.0 to − 1.5% and − 2.2 to − 5.0 kg, respectively) than with comparators (except for similar HbA1c reductions vs liraglutide). There were no statistically significant interactions by treatment and background medication subgroup for change in HbA1c or body weight except for change in HbA1c (background insulin vs insulin plus metformin) in PIONEER 8 (p = 0.0408). Changes in HbA1c and body weight were generally similar across insulin regimen subgroups, without significant treatment interactions by subgroup, and the total daily insulin dose was decreased for patients receiving oral semaglutide. The incidence of adverse events was generally similar in background medication subgroups.ConclusionOral semaglutide was effective at lowering HbA1c and body weight, regardless of background medications, and appears suitable for a broad range of patients with T2D in combination with other glucose-lowering agents.Trial RegistrationClinicaltrials.gov: NCT02607865 (PIONEER 3), NCT02863419 (PIONEER 4), NCT02827708 (PIONEER 5), NCT02849080 (PIONEER 7) and NCT03021187 (PIONEER 8).Graphic Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-020-00994-9.

Outcomes of transition from premixed and intensive insulin therapies to insulin aspart/degludec co-formulation in type 2 diabetes mellitus: a real-world experience.

IntroductionTo evaluate the efficacy and safety of transition from premixed and intensive insulin to twice-daily insulin degludec/aspart (IDegAsp) co-formulation in patients with type 2 diabetes mellitus.Material and methodsIn this 12-week study, patients receiving twice-daily premixed insulin therapy in group 1 (n = 55) were switched to twice-daily IDegAsp. In group 2 (n = 60), patients on intensive insulin therapy were switched to IDegAsp injected twice a day. Inter- and intragroup comparisons were made.ResultsA total of 115 patients were included in the study. There was a significant improvement in glycaemic control, median daily total insulin dose, body mass, body mass index, and hypoglycaemic events in group 1 and group 2 with the switch to IDegAsp (p < 0.05). The decrease in median daily total insulin dose requirement in group 2 was higher than that of group 1 (p = 0.001). There was no difference between groups in terms of other parameters (p > 0.05).ConclusionsThe current analysis indicates that IDegAsp treatment improves outcomes, with the most notable differences observed in daily total insulin requirement, body mass, and hypoglycaemia.

Continuous glucose monitoring systems in well-controlled children with type 1 diabetes mellitus.

Numerous studies have demonstrated the clinical benefits of using continuous glucose monitoring (CGM) systems among patients with type 1 diabetes (T1D). Aim of the study was to assess the effectiveness of CGM on metabolic control in children with T1D and well-controlled disease prior to the study. This prospective analysis included 99 children (46 girls) at the median age of 11.23 years and diabetes duration of at least 1 year (median: 5.16 years), generally well controlled metabolically (median HbA1c: 7.0%), and treated with continuous subcutaneous insulin infusion (CSII). The patients had used CGM for at least 150 days. We analysed the participants in subgroups based on baseline HbA1c<7%, ≥ 7%, age, and sex. Children with baseline HbA1c<7% were characterized by significantly increased HbA1c after the median of 273 days (217; 320) of CGM usage (6.3% vs. 6.6%, respectively; p=0.002). No significant change in HbA1c was noted in children with baseline HbA1c ≥ 7% (7.5% vs. 7.4%, respectively; p=0.191), but 20% of the group reached the target of HbA1c<7.0%. The analysis of CGM data revealed that no group achieved the CGM targets of good metabolic control. Total daily insulin requirements remained stable in both groups (p=0.752; p=0.274), but the amount of basal insulin increased statistically in both groups (p=0.009; p ≤ 0.001). The application of CGM provides detailed information concerning glycaemic control and is beneficial in some, but not all, T1D children with good diabetes control.

Real-world study on the effectiveness and safety of basal insulin IDegLira in type 2 diabetic patients previously treated with multi-injective insulin therapy.

Achieving glycemic target is paramount to control diabetes mellitus (DM) and reduce micro-vascular and macro-vascular complications. Despite the mostly recent-developed drugs, most patients still show an above desired glycated hemoglobin (HbA1c) level due to DM complex pathophysiology, therapeutic and dietary compliance and clinical inertia in introducing or intensifying insulin therapy. To support the promising results of clinical trials on the effectiveness and safety of the degludec/liraglutide combination (IDegLira) in type 2 DM patients with C-peptide values >1 ng/ml who were previously treated with basal-bolus multiple daily-dose insulin injections. This observational, prospective and non-randomized trial enrolled type 2 DM patients referred to our outpatient clinic between January 2019 and December 2019, who were shifted from multiple daily-dose insulin injection therapy to degludec/liraglutide combination as per the physician's decision. The main assessment was HbA1c variation at 6 months from baseline. Secondary assessments included variation in fasting glycemia, routine anthropometric assessments, blood chemistry, blood pressure and patients' quality of life (measured by the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), from baseline to 6 months. HbA1c (8.4 vs. 7.4%; p<0.0001) and body weight (94.1 vs. 93 kg; p<0.0001) were significantly lower after 6 months for patients on the degludec/liraglutide combination. A similar trend was observed in fasting glycemia levels (159 vs. 125 mg/dl; p<0.0001). An improved glycemic control was achieved with degludec/liraglutide despite a reduction in total daily insulin units (42 U at 6 months vs. 22 U at baseline; p<0.0001). In addition, higher scores in the DTSQ were registered after 6 months on degludec/liraglutide (mean score: 27 vs. 20; p<0.0001). The combination therapy also proved more convenient than basal-bolus therapy in terms of costs, with an average per-patient cost difference of €-0.41±0.59/die (p<0.0001). These real-world findings show that degludec/liraglutide seems to be more effective than basal-bolus insulin in achieving glycemic control, allowing cost sustainability and improving patient satisfaction.

PDB62 Profile of Patients Treated with Insulin Lispro 200 U/ML in the Real World: Profile IL-200 Study

There are limited data on the use of insulin lispro 200 U/mL (IL200) in clinical practice in Spain. This real world study (PROFILE-IL200) describes the clinical/demographic characteristics, and treatment, of patients who initiate IL200 therapy. This retrospective observational study based on the IQVIA medical records database in Spain included adult (≥18 years) patients with type 1 (T1D) and type 2 (T2D) diabetes who initiated IL200 between 1st June 2015 and 31st December 2019. The patients’ demographic and clinical characteristics on the index date (date of IL200 initiation), medical history, initial dose of IL200, previous and concomitant antidiabetic therapy were analysed descriptively by diabetes type. Total daily insulin dose (U) before index was calculated as the mean of basal and rapid insulin prescriptions available in the 90-day pre-index period, and at index with prescriptions in the following 60 days. Main characteristics for the T1D/T2D groups (N=65/167) were, respectively: male, 63.1%/55.7%; mean (standard deviation [SD]) age, 46.5 (15.5)/62.6 (12.8) years; time since diagnosis, 6.6 (4.2)/7.9 (2.9) years; body mass index, 30.9 (5.8)/33.1 (5.5) kg/m2; HbA1c 8.3 (2.1)/8.8 (1.8)%; diabetes-associated comorbidity present, 55.4%/92.8%. Fourteen patients were new diagnoses. Among T1D/T2D with a prior diagnosis (N=54/164), 96.3%/90.2% had previous insulin, (rapid insulin in 81.5%/62.2%); 13.0% (n=7)/97.6% previous non-insulin antidiabetic therapy. The mean (SD) insulin dose pre-index for T1D/T2D was 98 (73.9)/95.2 (59.8) U/day. IL200 was initiated at a mean (SD) dose of 56.3 (43.8) and 51.5 (34.3) U/day for T1D/T2D, with basal insulin in 86.2%/83.2%. IL200 was first prescribed by an endocrinologist (48.7%), and by the general practitioner in 46.6% of patients. This is the first study that describes the profile of patients treated with IL200 in clinical practice in Spain. These T1D and T2D patients presented a high body mass index, associated comorbidities and received high doses of insulin at IL200 initiation.

Efficacy, safety and cost-effectiveness comparison between U-100 human regular insulin and rapid acting insulin when delivered by V-Go wearable insulin delivery device in type 2 diabetes

IntroductionWe compared the efficacy and safety of human regular insulin (HRI) versus rapid-acting insulin (RAI) in a type 2 diabetes population already using the V-Go insulin delivery device.Research design and...

Determinants of High-Dose Insulin Usage and Upper Extremity Muscle Strength in Adult Patients With Type 2 Diabetes

ObjectivesIn this study, we aimed to determine the association between upper extremity muscle strength and insulin dose in patients with type 2 diabetes. MethodsA total of 236 patients with type 2 diabetes under insulin treatment for at least 1 year were included in this cross-sectional study. Patients were divided into 3 groups based on their total daily insulin dose (TDID): group 1, TDID >2 U/kg/day or >200 units/day; group 2, TDID 1 to 2 U/kg/day or 51 to 199 U/day; and group 3, TDID <0.5 U/kg/day or 50 U/day. High-dose insulin use was defined as total daily insulin dose >2 U/kg or >200 U/day. Muscle strength was measured using a handgrip dynamometer. ResultsHigh-dose insulin users were younger and had higher measures of generalized and central obesity and glycated hemoglobin. There was no significant difference in muscle strength between the groups. Low muscle strength was seen in 26.7% of all patients. Patients with low muscle strength were older, had lower insulin dose treatment and had better glycemic control than patients with normal muscle strength. Handgrip strength was inversely correlated with age, body mass index and duration of diabetes, but not with TDID. ConclusionsPatients with type 2 diabetes with high-dose insulin use had similar upper extremity muscle strength measurements with standard-dose insulin users. Studies with more patients are needed to determine the relationship between muscle mass, muscle strength and high-dose insulin use.

Effects of GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Heart Transplant Patients with Type 2 Diabetes: a Case Series

Background Type 2 diabetes mellitus (T2D) is common in post-heart transplant patients. Commonly used T2D medications, especially insulin, can promote weight gain and are not associated with cardiovascular (CV) benefits. Glucagon-like Peptide-1 receptor agonists (GLP-1 RA) and Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) are two drug classes that produce CV benefits in T2D and promote weight loss with minimal risk of hypoglycemia. Their use has not been previously evaluated in this particular group, and there have been theoretical concerns about safety in immunosuppressed patients. Methods Patients with T2D are sequentially referred by the Heart Transplant program to the Cardiometabolic Center of Excellence (CMCE) at our institution, allowing minimal selection bias. CMCE provides treatment algorithms that emphasize the use of cardioprotective T2D medications. We analyzed this initial series of transplant patients with T2D who have been on GLP-1 RA and/or SGLT-2i with at least two visits at CMCE. Results Among 15 patients, the mean age was 59.4 ± 2.6 years, 66.7% were males, 73.3% were Caucasians, 33.3% had history of ischemic cardiomyopathy and baseline eGFR was 53.5 ± 7.9 mL/min/1.73m2. The median time from transplant was 4.6 (1.6 - 10.5) years. The median follow-up time at CMCE was 5.4 (2.8 - 10.9) months. At baseline, 73% were on insulin, 40% on Metformin, 13% on Sulfonylurea, 13% on Dipeptidyl peptidase-4 inhibitors, and 7% on Thiazolidinediones. Following initiation of therapy at CMCE, 86.7% of patients were on a combination of GLP-1 RA and SGLT-2i, while the rest were taking only GLP-1 RA. Overall, the median total daily insulin requirements decreased substantially from 94 (40.5 - 124) to 34 (5 - 60) units at latest clinic visit; p = 0.003. Further, median hemoglobin A1c dropped from 7.7% (7.3 - 9.5) to 6.6% (6 - 8.5); p = 0.007. There was also a significant reduction in mean body weight (241.9 ± 35.8 at baseline vs. 217.1 ± 34.2 lbs at follow-up; p = 0.001), and mean body mass index (34.9 ± 4.5 vs. 31.1 ± 3.7; p = 0.001). Only one patient experienced side effects as one episode of severe nausea with Liraglutide that resolved when switched to Semaglutide. No infectious complications (including urinary tract or genital mycotic infections) were observed. Conclusions In this limited case series, combination therapy with GLP-1 RA and SGLT-2i was well tolerated in heart transplant patients and associated with favorable results in insulin requirement, hemoglobin A1c, and body weight. Type 2 diabetes mellitus (T2D) is common in post-heart transplant patients. Commonly used T2D medications, especially insulin, can promote weight gain and are not associated with cardiovascular (CV) benefits. Glucagon-like Peptide-1 receptor agonists (GLP-1 RA) and Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) are two drug classes that produce CV benefits in T2D and promote weight loss with minimal risk of hypoglycemia. Their use has not been previously evaluated in this particular group, and there have been theoretical concerns about safety in immunosuppressed patients. Patients with T2D are sequentially referred by the Heart Transplant program to the Cardiometabolic Center of Excellence (CMCE) at our institution, allowing minimal selection bias. CMCE provides treatment algorithms that emphasize the use of cardioprotective T2D medications. We analyzed this initial series of transplant patients with T2D who have been on GLP-1 RA and/or SGLT-2i with at least two visits at CMCE. Among 15 patients, the mean age was 59.4 ± 2.6 years, 66.7% were males, 73.3% were Caucasians, 33.3% had history of ischemic cardiomyopathy and baseline eGFR was 53.5 ± 7.9 mL/min/1.73m2. The median time from transplant was 4.6 (1.6 - 10.5) years. The median follow-up time at CMCE was 5.4 (2.8 - 10.9) months. At baseline, 73% were on insulin, 40% on Metformin, 13% on Sulfonylurea, 13% on Dipeptidyl peptidase-4 inhibitors, and 7% on Thiazolidinediones. Following initiation of therapy at CMCE, 86.7% of patients were on a combination of GLP-1 RA and SGLT-2i, while the rest were taking only GLP-1 RA. Overall, the median total daily insulin requirements decreased substantially from 94 (40.5 - 124) to 34 (5 - 60) units at latest clinic visit; p = 0.003. Further, median hemoglobin A1c dropped from 7.7% (7.3 - 9.5) to 6.6% (6 - 8.5); p = 0.007. There was also a significant reduction in mean body weight (241.9 ± 35.8 at baseline vs. 217.1 ± 34.2 lbs at follow-up; p = 0.001), and mean body mass index (34.9 ± 4.5 vs. 31.1 ± 3.7; p = 0.001). Only one patient experienced side effects as one episode of severe nausea with Liraglutide that resolved when switched to Semaglutide. No infectious complications (including urinary tract or genital mycotic infections) were observed. In this limited case series, combination therapy with GLP-1 RA and SGLT-2i was well tolerated in heart transplant patients and associated with favorable results in insulin requirement, hemoglobin A1c, and body weight.

Effects of Sodium-Glucose Cotransporter Inhibitor/Glucagon-Like Peptide-1 Receptor Agonist Add-On to Insulin Therapy on Glucose Homeostasis and Body Weight in Patients With Type 1 Diabetes: A Network Meta-Analysis.

Many patients with type 1 diabetes (T1D) do not achieve the glycemic target goal with insulin treatment. In this study, we aimed to evaluate the efficacy and safety of add-on to insulin therapy in patients with T1D. We conducted direct and indirect network meta-analyses using Bayesian models and ranked hypoglycemic agents via mixed treatment comparison, using data from the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases. Randomized controlled trials (RCTs) involving patients with T1D treated with insulin and add-on metformin or sodium-glucose cotransporter inhibitors or glucagon-like peptide-1 receptor agonists from January 1970 to September 2019 were included in this study. Twenty-three RCTs with 5,151 subjects were divided into the following groups: insulin alone, insulin+metformin, insulin+canagliflozin, insulin+dapagliflozin, insulin+empagliflozin, insulin+sotagliflozin, insulin+liraglutide, and insulin+exenatide. HbA1c level in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group (mean difference: −0.43, 95% credible interval: −0.62 to −0.23). Total daily insulin dose in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group. Compared with that in the insulin alone group, body weight in the groups treated with insulin+add-on canagliflozin, sotagliflozin, and exenatide was significantly decreased by 4.5, 2.8, and 5.1 kg, respectively. Hypoglycemic episodes did not differ among the groups. In patients with T1D, insulin+sotagliflozin decreased the HbA1c level, daily insulin dose, and body weight without hypoglycemia compared with insulin monotherapy. Insulin+canagliflozin or insulin+exenatide was effective in reducing body weight compared with insulin alone. In conclusion, sotagliflozin treatment decreased not only the HbA1c levels and insulin dose but also the body weight without causing hypoglycemia in patients with T1D. Treatment with canagliflozin and exenatide effectively reduced body weight in patients with T1D. However, ketoacidosis associated with the use of SGLT inhibitors should be considered in these patients. Thus, our results suggest that sotagliflozin has a high probability of being ranked first as an adjunctive therapy to insulin in patients with T1D.

Effect of adherence to carbohydrate counting on metabolic control in children and adolescents with type 1 diabetes mellitus.

PurposeCarbohydrate counting provides better glycemic control and flexibility than other food planning methods. Consistent adherence to such a complex method is difficult, especially for youth. However, studies that determine adherence to this method and whether it alters metabolic control are limited. The aim of the current study was to determine adherence to this method and investigate its effect on metabolic control, anthropometric measurements, insulin dose, and energy intake.MethodsIn this prospective cross-sectional study, 53 children and adolescents with type 1 diabetes mellitus aged 2 to18 years and receiving intensive insulin therapy were trained and followed for 6 months. Demographics, anthropometrics, insulin requirements, hemoglobin A1c (HbA1c), fasting lipids, and food records at baseline and study conclusion were evaluated. At the end of the study patients were divided into adherer and nonadherer groups according to carbohydrate estimate deviations from standardized daily sample menus and calculations for accurate insulin doses. More than 10-g variation in daily consumed carbohydrate amount or failure to decide bolus insulin dose was defined as a nonadherer.ResultsThe mean HbA1c, low-density lipoprotein cholesterol, and body mass index standard deviation score changed after the carbohydrate counting training while the mean HbA1c between groups was significant (P<0.05). Total daily insulin doses increased, and the mean high-density lipoprotein cholesterol levels decreased in both groups. There were significant correlations between HbA1c and carbohydrate deviation scores as well as HbA1c and caregiver's education level.ConclusionsSince adherence to carbohydrate counting may affect metabolic control, health professionals should evaluate and monitor carbohydrate counting skills of caregivers and patients in order to improve efficiency.

Impact of a Weekly Glucagon-Like Peptide 1 Receptor Agonist, Albiglutide, on Glycemic Control and on Reducing Prandial Insulin Use in Type 2 Diabetes Inadequately Controlled on Multiple Insulin Therapy: A Randomized Trial.

OBJECTIVEThe principle of replacing prandial insulin lispro with a once-weekly glucagon-like peptide 1 receptor agonist (GLP-1RA) for type 2 diabetes inadequately controlled on a multiple daily insulin injections regimen was tested with albiglutide.RESEARCH DESIGN AND METHODSIn this treat-to-target study, basal plus prandial insulin was optimized over 4 weeks before participants were randomized (1:1) to albiglutide plus optimized basal insulin glargine and lispro (dose reduced by 50% at randomization; subsequently, lispro injections were fully discontinued 4 weeks later) (n = 402) or to continued optimized lispro plus optimized glargine (n = 412).RESULTSMean ± SD HbA1c at baseline, 7.8 ± 0.6% (61 ± 7 mmol/mol) in the albiglutide + glargine group and 7.7 ± 0.6% (60 ± 7 mmol/mol) in the lispro + glargine group, was reduced at week 26 to 6.7 ± 0.8% (49 ± 8 mmol/mol) and 6.6 ± 0.8% (48 ± 8 mmol/mol), respectively (least squares [LS] difference 0.06% [95% CI −0.05 to 0.17]; noninferiority P < 0.0001). In the albiglutide + glargine group, 218 participants (54%) replaced all prandial insulin without reintroducing lispro up to week 26. Total daily prandial insulin dose was similar at baseline but was lower by 62 units/day (95% CI −65.9 to −57.8; P < 0.0001) at week 26 in the albiglutide + glargine group, and the total number of weekly injections was also reduced from 29 to 13 per week. Less severe/documented symptomatic hypoglycemia (57.2% vs. 75.0%) occurred in the albiglutide + glargine group with meaningful weight differences (LS mean ± SE −2.0 ± 0.2 vs. +2.4 ± 0.2 kg; P < 0.0001) vs. lispro + glargine. Gastrointestinal adverse events were higher with albiglutide + glargine (26% vs. 13%).CONCLUSIONSA once-weekly GLP-1RA was able to substitute for prandial insulin in 54% of people, substantially reducing the number of prandial insulin injections; glycemic control improved, with the added benefits of weight loss and less hypoglycemia in the GLP-1RA arm. Replacing prandial insulin with a weekly GLP-1RA can simplify basal plus prandial insulin treatments and achieve better outcomes in type 2 diabetes.

126-LB: Glycemic Outcomes for People with Type 1 and Type 2 Diabetes Using Control-IQ Technology: Real-World Data from Early Adopters

The Food and Drug Administration recently cleared the t:slim X2 with Control-IQ technology in the United States. This advanced hybrid closed-loop system automatically adjusts insulin based on predicted sensor glucose (SG) levels to help increase sensor time in range (TIR) (70-180 mg/dL). The pivotal DCLP3 trial demonstrated noteworthy glycemic improvements in people with type 1 diabetes (PwT1D) using Control-IQ technology. However, DCLP3 did not include people with type 2 diabetes (PwT2D). We performed retrospective analysis of users who uploaded at least 14 days of pre and 14 days of post Control-IQ software usage data to Tandem’s t:connect® web application as of March 11, 2020 and had ≥75% CGM use during this time. Glycemic outcomes, total daily insulin (TDI), and time in closed loop were analyzed by diabetes type. Of the 3,278 PwDs included in the sample, 144 had T2D, 52% were female, mean age=43 years (SD=17.47), diabetes duration=23 years (SD=15). Wilcoxon signed-rank tests were used to examine pre-post differences in outcomes by diabetes type. Post 14-day Control-IQ technology use, PwT1Ds recorded 96% time in closed loop and showed significant improvements in their TIR (+9% from pre, p&amp;lt;0.001), reduced time in SG&amp;lt;70 (-0.04% from pre, p&amp;lt;0.001), and SG&amp;gt;180 (-8.45% from pre, p&amp;lt;0.001). Median TDI at post was 48 units (pre=46 units, p&amp;lt;0.001). Similar trends were observed for the type 2 sample, in that PwT2Ds recorded 96% time in closed loop and showed significant improvements in TIR (+6% from pre, p&amp;lt;0.001) and reduced SG time &amp;gt;180 (-5.8% from pre, p&amp;lt;0.001). Median SG time &amp;lt;70 remained unchanged (0.2%). Median total daily insulin for PwT2Ds increased to 82 units from pre-CIQ use of 73 units (p=0.003). These results from early adopters of Control-IQ technology confirm its efficacy in assisting both PwT1Ds and PwT2Ds achieve their recommended glycemic targets and improve their glycemic control. Disclosure S. Habif: Employee; Self; Tandem Diabetes Care. A. Constantin: Employee; Self; Tandem Diabetes Care. Other Relationship; Self; Bigfoot Biomedical. L. Mueller: Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. H. Singh: Employee; Self; Tandem Diabetes Care.

95-LB: Control-IQ Technology in the Real World: The First 30 Days

The t:slim X2 insulin pump with Control-IQ technology from Tandem Diabetes Care, Inc. was cleared by the Food and Drug Administration in December 2019. This study examined the commercial introduction of Control-IQ technology in the U.S. We performed a retrospective analysis of users who uploaded at least 30 days of pre and 30 days of post Control-IQ software update usage data to Tandem’s t:connect® web application as of March 11, 2020 and had ≥75% CGM use during this time (n=1,659). Outcomes included total daily insulin and sensor glucose values during open and closed-loop use of Control-IQ technology. Changes in glycemic outcomes were analyzed using the Wilcoxon signed-rank test. The mean age of patients was 43 years, 52% female, and mean diabetes duration was 21 years. Ninety percent of patients reported type 1 diabetes, 4% type 2 diabetes, and 6% “other” or unknown. The Control-IQ software update led to a 10% increase (p&amp;lt;0.001) of median sensor time in range (70-180 mg/dL) to 78% (IQR =69%-85%) due to a 10% decrease in sensor time &amp;gt;180mg/dL to 21% (IQR= 13%-30%) and a 0.1% decrease of sensor time &amp;lt;70mg/dL to 1.1.% (IQR=0.5%-2.2%). Improvements in sensor time in range were consistent across age groups. Mean sensor glucose fell from 161 mg/dL to 148 mg/dL while the median total daily insulin increased from 48u to 49u. Median time in closed-loop was 96% (IQR = 93%-98%). These real-world data demonstrate improved sensor time in range without increasing hypoglycemia. Disclosure L. Mueller: Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. A. Constantin: Employee; Self; Tandem Diabetes Care. Other Relationship; Self; Bigfoot Biomedical. H. Singh: Employee; Self; Tandem Diabetes Care. S. Habif: Employee; Self; Tandem Diabetes Care.