Insulin Analogues Glargine Research Articles

822-P: Influence of the Functionally Selective Insulin Analog NNC-965 vs. Insulin Glargine (IGla) on Cardiac Structure and Function

822-P: Influence of the Functionally Selective Insulin Analog NNC-965 vs. Insulin Glargine (IGla) on Cardiac Structure and Function

The IDEAL (Insulin therapy DE-intensificAtion with iglarLixi) Randomised Controlled Trial-Study Design and Protocol.

Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently asubstantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100U/ml and a GLP-1 RA lixisenatide. Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor. The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated. ClinicalTrials.gov, identifier NCT04945070.

Improvement of blood glucose control and reduction of hypoglycemia, body weight, and C-reactive protein in type 1 diabetic patients treated with intensive insulin therapy with insulin analogs

Background/Aim. Good metabolic control can delay the onset and progression of chronic complications of diabetes mellitus (DM). Intensified insulin therapy (IIT) is the cornerstone of good metabolic control in the treatment of type 1 DM (T1DM) while avoiding hypoglycemia and body weight (BW) gain in those patients. The aim of the study was to assess the effects of IIT with insulin analogs (aspart and glargine) in T1DM patients. Methods. This prospective clinical study included 49 patients with at least one year of T1DM duration, who were on IIT with human insulin at that moment. They commenced therapy with insulin aspart for three months, followed by insulin glargine for another three months. An analysis of blood glucose (BG) control (glycated hemoglobin ? HbA1c, mean BG, fasting BG, postprandial BG, and glycemic variability) and analysis of BW, hypoglycemia, and C-reactive protein (CRP) levels were performed. Results. The HbA1c level decreased slightly (non-significantly) after three months of insulin aspart therapy (from 9.28% to 8.83%) and decreased significantly after the aspart/glargine combination (to 8.08%; p < 0.001). After the first three months with aspart therapy, a significant reduction in postprandial BG was noted after all three main meals. The mean postprandial rise of BG was significantly reduced. The variability of daily BG was significantly reduced (standard deviation of BG fell from 2.28 mmol/L to 1.90 mmol/L; p < 0.05). The mean BG value in the profiles decreased (from 9.11 mmol/L to 8.31 mmol/L; p < 0.05). All BG values in the profiles after six months were statistically significantly lower compared to the initial values, as well as the mean BG (6.88 mmol/L; p < 0.001) and the variability of daily BG (1.49 mmol/L; p < 0.01). Our results showed a significant reduction in the number of hypoglycemias after three months, especially after the introduction of insulin glargine therapy (significant reduction in the number of symptomatic, asymptomatic, and nocturnal hypoglycemias). The results showed a discrete but significant reduction in BW and a significant reduction in CRP levels (from 3.43 mg/L to 2.25 mg/L; p < 0.001). Conclusion. Treatment of patients with T1DM with insulin analogs (insulin aspart and insulin glargine) in IIT leads to improved BG control with a reduction in the number of hypoglycemia, BW, and CRP levels.

Second Generation Basal Insulin, Degludec, in the Management of Diabetes; Consensus Report

The best anti-diabetic medication does, in fact, have a low propensity to increase body weight and rate of hypoglycemia as well as glycemic control. The second-generation basal insulins analogues insulin degludec and insulin glargine 300 units/mL have significantly longer half-life and substantially smoother profiles than firstgeneration. The duration of action of glargine 300 is shorter than that of degludec, and significant residual glycemic variability is still present. Degludec has lower risks of hypoglycemia. Evaluating the therapeutic application in various geographical contexts is necessary, given the inter-country variations in the prescription patterns of glucose-lowering medications for persons with diabetes. A Saudi task force gathered to develop an explicit, evidence-based consensus for insulin degludec utilization in the local setting. This work contains the expert panel's recommendations as a contribution to complement the knowledge gap in this area from the national perspective. Results of the local UPDATES study investigating the treatment effect of degludec in adults with T2DM in Saudi Arabia showed that patients treated with degludec experienced clinically significant improvements in glycaemic control and a lower rate of hypoglycemia compared to baseline, with no new safety concerns. Results confirm that previously published data with degludec are generalizable to a broad population of patients with T2DM in routine clinical practice in Saudi Arabia. Moreover, local cost-utility analyses of degludec versus glargine 300 in T1DM and T2DM showed that it is cost-saving. Degludec was associated with less cost with better quality of life. Thus, the reimbursement of degludec will have a positive impact on the budget.

Real-World Persistence, Adherence, Hypoglycemia, and Health Care Resource Utilization in People With Type 2 Diabetes Who Continued With the Second-Generation Basal Insulin Analog Insulin Glargine 300 Units/mL or Switched to a First-Generation Basal Insulin (Insulin Glargine 100 Units/mL or Detemir 100).

People with type 2 diabetes receiving a second-generation basal insulin (BI) analog may be switched to a first-generation formulation for financial reasons or changes in health insurance. However, because second-generation BI analogs have more even pharmacokinetic profiles, longer durations of action (>24 vs. ≤24 hours), and more stable action profiles than first-generation BI analogs, such a change may result in suboptimal treatment persistence and/or adherence. This study compared treatment persistence, treatment adherence, rates of hypoglycemia, and health care resource utilization outcomes in people with type 2 diabetes who either continued treatment with the second-generation BI Gla-300 or switched to a first-generation BI. The study showed that continuing with Gla-300 was associated with a lower risk of discontinuing therapy, fewer emergency department visits, and lower hypoglycemia event rates than switching to a first-generation BI.

PSUN278 Factitious hypoglycemia, diagnostic delay due to insulin assay failure to detect insulin analogues.

Abstract Factitious hypoglycemia may be difficult to diagnose clinically. Hypoglycemia due to insulin self-administration is established by the presence of a low c-peptide and elevated plasma insulin levels. Commercial insulin assays often fail to detect insulin analogs and can create confusion among providers investigating causes of hypoglycemia. A 20 year old female with no significant past medical history presented to an Emergency Room (ER) with hypoglycemia. She was treated with a single dose of octreotide 150 mcg, dexamethasone 10 mg PO and started on a D10W drip at 100ml/hr prior to transfer. Laboratory studies on transfer reported plasma glucose 52ng/dL (RR: 70-100), low C-peptide 0.02 (RR: 0.78-5.19), low insulin level <0.087 uIU/mL, normal IGF-I level 122 ng/mL (RR: 85-370). Normal IGF-II level 401 ng/mL (RR: 333-967), and low Pro-insulin level 1.8 pmol/L (RR: 3.6-22 pmol/L). Sulfonylurea Screen was negative. The patient and her mother both denied exogenous insulin use. The patient and her mother both work in healthcare. The patient's boyfriend has type 1 diabetes mellitus and the patient stated she keeps insulin in her purse for him. The patient was admitted for a 72 hour fast and remained normoglycemic. An aliquot of the admission ER insulin blood sample was sent to second laboratory utilizing an assay able to detect analog insulins. The patient's sample previously reporting an undetectable insulin level (<0.087 uIU/mL) now reported an insulin level 8 uIU/mL. Factitious hypoglycemia is a challenging clinical diagnosis. The term factitious implies an attempt to deceive and creates mistrust between the physician and patient. However, hypoglycemia may be the result of medication errors or administered by a second party with the intent to harm. Analog insulins (glargine, aspart, lispro, glulisine, etc) are genetically modified insulins developed to mimic the physiologic pattern of pancreatic beta cell insulin secretion. The amino acid modifications in analog insulins result in structural variations which alters the ability of highly specific commercial automated immunoassays to accurately quantitate these analog insulins. The variation in lab assay detection may cause confusion when interpreting the results. The DiaSorin Liaison XL platform in our hospital utilizes a chemiluminescence immunoassay which does not detect insulin analogs, but detects regular and NPH insulin as they are structurally identical to endogenous human insulin. The second laboratory uses the Siemens Advia Centaur platform, an immunoassay which reacts with insulin analogs "on a nearly equimolar basis with the analogs insulin aspart, insulin glargine, and insulin lispro. Insulin detemir exhibits approximately 50 percent cross-reactivity. Test reactivity with insulin glulisine is negligible (< 3 percent)". Many commercial insulin assays do not detect analog insulins and none qualitatively distinguish between different insulins. Failure to recognize this detection flaw may result in misdiagnosis, patient safety issues and costly unneeded additional studies Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Efficacy and Tolerability of Insulin Degludec Versus Other Long-acting Basal Insulin Analogues in the Treatment of Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

PurposeThe goal of this study was to compare the efficacy and tolerability of insulin degludec with those of other long-acting insulin analogues (insulin glargine and insulin detemir) in patients with type 1 or 2 diabetes mellitus (T1D or T2D). MethodsThose randomized controlled trials comparing insulin degludec with other long-acting insulin analogues in the treatment of patients with T1D or T2D published on or before August 21, 2022, were retrieved from PubMed, Web of Science, the Cochrane Library, and EMBASE. The efficacy end points were the changes from baseline in hemoglobin A1c and fasting plasma glucose (FPG). The tolerability end point was the prevalence of hypoglycemia confirmed throughout the treatment period. FindingsData from a total of 20 trials (19,048 patients) were included. The differences in the reductions in glycosylated hemoglobin between insulin degludec and other long-acting basal insulin analogues (insulin glargine and insulin detemir) used for the treatment of patients with T1D or T2D were not significant. However, the reduction in FPG was greater with insulin degludec (–0.370 mmol/L; 95% CI, –0.473 to –0.267 mmol/L; P ≤ 0.001). Throughout the treatment periods of all of the available trials, the estimated rate ratios of overall and nocturnal hypoglycemia were significantly decreased with insulin degludec compared with insulin glargine or insulin detemir in patients with T1D or T2D; the differences in the risks for severe hypoglycemia were not significant. ImplicationsCompared with other long-acting insulin analogues (insulin glargine and insulin detemir), insulin degludec was associated with a significantly decreased FPG, with lower prevalences of overall and nocturnal hypoglycemia.

ATOS study: effectiveness and safety of insulin glargine 300 U/mL in the real world clinical practice in insulin-naïve type 2 diabetic patients in the Russian Federation

Rationale: Basal insulin glargine 300 U/mL (Gla-300) is a second-generation basal insulin analogue that has comparable efficacy and lower variability compared to the first generation long-acting insulin analogue glargine 100 U/mL.
 Aim: To assess the effectiveness and safety of Gla-300 in insulin-nave type 2 diabetic patients in the real world practice in Russia.
 Materials and methods: ATOS (NCT03703869) was a 12-month, prospective observational international multicenter study. The study included 4422 adults ( 18 years) with uncontrolled type 2 diabetes (HbA1c 7 and 11%) with 1 oral anti-hyperglycemic drug and for whom the treating physician had decided to add Gla-300. We performed a post-hoc sub-analysis of the study participants recruited in Russia.
 Results: The Russian study group included 1493 patients receiving Gla-300. At 6 months, 25.9% of the patients achieved their predefined individualized HbA1c target and 53.3% achieved their HbA1c target at month 12. Their mean ( SD) HbA1c level decreased from 9.3 0.9% at baseline to 7.6 0.7% and 7.2 0.7 at months 6 and 12. The incidence of hypoglycemia was generally low; overall, severe hypoglycemia was reported only in 0.07% and 0.13% of the patients at 6 and 12 months. The baseline average daily dose of Gla-300 was 13.2 4.9 Units; it to 23.6 9.1 and 26.0 9.8 Units at months 6 and 12.
 Conclusion: In the real world setting, initiation of insulin Gla-300 in type 2 diabetic patients who had been out of their target glucose range with oral hypoglycemic agents is associated with improved glycemic control and low risk of hypoglycemia.

105-LB: Glucose Variability with Second-Generation Basal Insulin Analogs Glargine 300 U/mL and Degludec 100 U/mL, Evaluated by CGM in People with T1D—The InRange Randomized Controlled Trial

Background: InRange has previously demonstrated that insulin glargine 300 U/mL (Gla-300) is non-inferior to insulin degludec 100 U/mL (IDeg-100) in terms of time in glucose range 70--180 mg/dL (primary endpoint) and total glucose coefficient of variation (CV) as measured by CGM in people with T1D. Methods: InRange (NCT04075513) was a multicenter, randomized, active-controlled, parallel-group, 12-week open-label trial comparing Gla-300 vs. IDeg-100 in adults with T1D using 20-day CGM profiles (≥10 days evaluable) . Here we present data for within- and between-day CV. Results: Overall, 343 participants were randomized (172 Gla-300, 171 IDeg-100) : mean ± SD age was 42.8 ± 13.3 years and T1D duration was 20.5 ± 12.8 years. Both within-day and between-day glucose CV at Week 12 were similar with Gla-300 and IDeg-100 (Table) . Within-day glucose CV at Week 12 was below the threshold for glycemic stability (36%) in both groups and was also similar in both treatment groups irrespective of glycemic stability at baseline (CV ≤36% or >36%) . The LS mean within-day glucose CV of participants with CV >36% at baseline reached 33.67 (Gla-300) and 35.38 (IDeg-100) at Week 12. Conclusion: Using clinically relevant CGM metrics, InRange shows that Gla-300 and IDeg-100 provide similar within- and between-day glucose variability in people with T1D. Disclosure R. M. Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. T. Battelino: Advisory Panel; Abbott Diabetes, Indigo Diabetes, Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi, Research Support; Medtronic, Novartis Pharmaceuticals Corporation, Novo Nordisk, Zealand Pharma A/S, Speaker’s Bureau; Abbott Diabetes, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; DreaMed Diabetes, Ltd. S. Edelman: Consultant; Abbott Diabetes, Lilly Diabetes, Sanofi-Aventis U. S., Xeris Pharmaceuticals, Inc. P. Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker’s Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. T. Danne: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG, Research Support; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG, Stock/Shareholder; DreaMed Diabetes, Ltd. E. Renard: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Insulet Corporation, LifeScan, Lilly, Novo Nordisk, Roche Diabetes Care, Sanofi, Tandem Diabetes Care, Inc. J. Westerbacka: Employee; Sanofi, Stock/Shareholder; Sanofi. B. Mukherjee: Employee; Sanofi, Stock/Shareholder; Sanofi. P. Picard: n/a. V. Pilorget: None. Funding Sanofi

Real-world outcomes of addition of insulin glargine 300 U/mL (Gla-300) to glucagon-like peptide-1 receptor agonist (GLP-1RA)therapy in people with type 2 diabetes: The DELIVER-G study.

To provide real-world data on the addition of basal insulin (BI) in people with type 2 diabetes mellitus (PWD2) suboptimally controlled with glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. However, real-world data on the addition of BI to GLP-1RA therapy are limited. We used a US electronic medical record data source (IBM® Explorys®) that includes approximately 4 million PWD2 to assess the real-world impact of adding the second-generation BI analogue insulin glargine 300 U/mL (Gla-300) to GLP-1RA therapy. Insulin-naïve PWD2 receiving GLP-1RAs who also received Gla-300 between March 1, 2015 and September 30, 2019 were identified; participants were required to have data for ≥12 months before, and ≥6 months after, addition of Gla-300. The mean (standard deviation [SD]) age of participants (N=271) was 57.9 (10.8) years. Baseline glycated haemoglobin (HbA1c) was 9.16% and was significantly reduced (-0.97 [SD 1.60]%; P< 0.0001) after addition of Gla-300; a significant increase in the proportion of PWD2 achieving HbA1c control was observed after addition of Gla-300 (HbA1c <7.0%: 4.80% vs. 22.14%, P< 0.0001; HbA1c <8.0%: 19.56% vs. 51.29%, P< 0.0001). The incidence of overall (8.49% vs. 9.59%; P= 0.513) and inpatient/emergency department (ED)-associated hypoglycaemia (0.37% vs. 0.74%; P= 1.000), as well as overall (0.33 vs. 0.46 per person per year [PPPY]; P= 0.170) and inpatient/ED-associated hypoglycaemia events (0.01 vs. 0.04 PPPY; P= 0.466) were similar before and after addition of Gla-300. In US real-world clinical practice, adding Gla-300 to GLP-1RA significantly improved glycaemic control without significantly increasing hypoglycaemia in PWD2. Further research into the effect of adding Gla-300 to GLP-1RA therapy is warranted.

Effect of human insulin and insulin analogue on some inflammatory markers and total antioxidant capacity in a sample of Iraqi type 1 diabetic children and adolescents

Background: Both human insulin and insulin analogue used in the treatment of type 1 diabetes mellitus. The modification in amino acids sequences of human insulin lead to produce analogue form which have a pharmacokinetic and pharmacodynamics effect near to normal human endogenous&#x0D; &#x0D; insulin release.&#x0D; Aim of study: This study designed to compare between the effect of each type of insulin on high sensitive C-reactive protein and interleukin-6 and total antioxidant capacity in a sample of Iraqi type 1 diabetic children and adolescents.&#x0D; Study design: The study was enrolled on fifty-one Iraqi type 1 diabetic children and adolecence age range (6-18) year. The patients allocated into two groups, Group (1) includes 20 patients assigned to receive conventional human insulin (regular and NPH), and Group (2) includes 20 patients assigned to receive insulin analogue (insulin aspart and glargine) for three months. The inflammatory and antioxidant markers measured at baseline and after three months of intervention.&#x0D; Results: After three months of treatment, both insulin groups did not affect high sensetive C_reactive protein (hs-CRP) significantly from baseline to 3 months. Only insulin analogue reduced Interleukin-6 (IL-6) significantly, while human insulin reduced level of IL-6 but it was not statistically significant. Both therapies reduced total antioxidant capacity (TAOC) significantly; however, insulin analogue had higher reduction percentage (15.1% vs. 5.7%) compared to the conventional insulin.&#x0D; Conclusion: Only insulin analogue reduced IL-6 significantly. Both types of insulins did not effect on hs-CRP. Both therapies reduce TAOC significantly.

IDF21-0203 A1C Target Attainment Without Hypoglycemia According to BMI: Insulin Glargine 300 U/mL vs 1st-Generation Basal Insulin

Background: High BMI is associated with insulin resistance and greater basal insulin (BI) requirements, which can lead to increased risk of hypoglycemia. The real-life, pragmatic, randomized ACHIEVE Control study (NCT02451137) demonstrated that among insulin-naive adults with T2D ≥1 year and A1C 8–11%, those who received the 2nd-generation BI analog glargine 300 U/mL (Gla-300) were significantly more likely to achieve individualized A1C targets (<8% for participants ≥65 years or with defined comorbidities; <7% for all others) without documented symptomatic (≤70 mg/dL) and/or severe hypoglycemia versus first-generation BI analogs (insulin glargine 100 U/mL; insulin detemir) at 6 months, with the trend continuing at 12 months. Aim: This post-hoc analysis of ACHIEVE Control explored the correlation between A1C target attainment without hypoglycemia with daily insulin dose according to BMI. Method: Participants were categorized according to baseline BMI (<30, 30–<35, 35–<40, ≥40 kg/m2). Proportions of participants achieving individualized A1C targets without documented symptomatic (≤70 and <54 mg/dL) and/or severe hypoglycemia; mean daily insulin doses at 6 and 12 months were estimated. Results: The <30 kg/m2 BMI group comprised individuals who were predominantly male (61 vs 42–58%), were older (61.7 vs 55.1–59.7 years), and had longer duration of T2D (12.6 vs 9.8–11.2 years) versus those with higher BMIs. Mean A1C was 9.1–9.2% across all BMI subgroups. Background medication use was generally well balanced, except for higher GLP-1 RA use as BMI increased. The proportion of individuals with the more stringent A1C goal of <7% increased as BMI increased, likely related to their younger age. Insulin dose at 12 months (U/kg/day) was similar across all BMI categories (range: 0.351–0.395). At both 6 and 12 months, a numerically higher proportion of participants who received Gla-300 versus 1st-generation BIs achieved their individualized A1C target without documented symptomatic (at both ≤70mg/dL and <54 mg/dL) or severe hypoglycemia (except for the ≥40 kg/m2 group at 6 months) (Table). Discussion: The results of this post-hoc analysis were consistent with those of the primary endpoint of the overall ACHIEVE Control study. The trend for benefit of Gla-300 versus 1st-generation BI for achievement of individualized A1C target without documented symptomatic and/or severe hypoglycemia at 12 months was consistent regardless of BMI.

IDF21-0428 7-year Simulation of Clinical Outcomes In People With Type 2 Diabetes Treated With Insulin Glargine 300 U/mL vs 100 U/mL

Background: The long-acting basal insulin analogue insulin glargine is used to improve glycaemic control in people with type 2 diabetes (PWD2). Insulin glargine 100 U/mL (Gla-100) was shown to improve glycaemic control for PWD2 compared with standard-of-care in the 7-year follow-up from the ORIGIN trial (NCT00069784). More recently, a longer-acting insulin glargine 300 units/mL (Gla-300) was compared with Gla-100 in PWD2 in the non-inferiority EDITION-3 trial (NCT01676220); after 12 months, Gla-300 demonstrated similar glycaemic control compared with Gla-100.

Real-world persistence, adherence, health care resource utilization, and costs in people with type 2 diabetes switching from a first-generation basal insulin to a second-generation (insulin glargine 300 U/mL) vs an alternative first-generation basal insulin.

BACKGROUND: People with type 2 diabetes (T2D) who change their basal insulin (BI) may have variable persistence with therapy. Compared with first-generation (long-acting) BI analogs (insulin glargine 100U/mL [Gla-100]; insulin detemir [IDet]), second-generation (longer-acting) BI analogs (insulin glargine 300U/mL [Gla-300]; insulin degludec) have similar glycated hemoglobin (HbA1c) attainment and lowered hypoglycemia risk, which could impact treatment persistence. OBJECTIVE: To compare persistence, adherence, health care resource utilization (HRU), and costs for individuals switching from neutral protamine Hagedorn insulin or a first-generation BI analog with either the second-generation BI, Gla-300, or an alternative first-generation BI analog (Gla-100 or IDet). METHODS: We used Optum Clinformatics claims data from adults (aged ≥ 18 years) with T2D who had received BI (neutral protamine Hagedorn, Gla-100, IDet) in the 6-month baseline period, and switched to either Gla-300 or an alternative first-generation BI (Gla-100 or IDet; treatment switch = index date) between April 1, 2015, and August 31, 2019. Participants were followed for 12 months, until plan disenrollment, or until death, whichever occurred first. Cohorts were propensity score matched (PSM) on baseline characteristics. The primary outcome was the proportion who were persistent with therapy at 12 months. Secondary outcomes were adherence (proportion of days covered); change in HbA1c; and all-cause, diabetes-related, and hypoglycemia-related HRU and costs. RESULTS: PSM generated 3,077 participants/group (mean age: 68 years, 52% female). Cohorts were well balanced except for hospitalization, which was adjusted in models as a covariate. During the 12-month follow-up period, participants who received Gla-300 vs first-generation BI had greater persistence with (45.5% vs 42.1%; adjusted P = 0.0001), and adherence to (42.8% vs 38.2%; adjusted P = 0.0006), BI therapy and a statistically larger reduction in HbA1c at 12 months (-0.65% vs -0.45%; adjusted P = 0.0040). The proportion of participants achieving HbA1c less than 8% (47.2% vs 40.9%; P < 0.0001), but not less than 7% (21.2% vs 20.8%), was significantly higher for Gla-300 vs first-generation BI. All-cause (45.3 vs 65.9 per 100 patient-years [P100PY]) and diabetes-related (21.5 vs 29.1 P100PY), but not hypoglycemia-related, hospitalizations (1.0 vs 1.5 P100PY) were significantly (P < 0.0001) lower for Gla-300 vs first-generation BI. Similarly, all-cause (111.9 vs 148.8 P100PY), diabetes-related (54.8 vs 74.2 P100PY), and hypoglycemia-related (2.9 vs 5.7 P100PY) emergency department (ED) visits were significantly lower for Gla-300 (all P < 0.0001). Costs for all-cause hospitalizations and hypoglycemia-related ED visits were significantly lower for Gla-300 vs first-generation BI. Although pharmacy costs were significantly higher for Gla-300 vs first-generation BI, all-cause total health care costs were not significantly different: $41,255 vs $45,316 per person per year, respectively. CONCLUSIONS: In this claims-based analysis of people with T2D receiving BI, switching to Gla-300 was associated with significantly better persistence, adherence, and HbA1c reduction compared with switching to an alternative first-generation BI analog. All-cause HRU was significantly lower; despite significantly higher pharmacy costs, total health care costs were similar. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Helen Jones, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Wright is on the speakers' bureau and sits on the advisory boards for Abbot Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, and Sanofi; sits on the advisory board for Medtronic; and is a consultant for Abbot Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly. Dr Malone is on advisory boards for Novartis and Avalere and consults for Pear Therapeutics, Sarepta, and Strategic Therapeutics. Dr Trujillo sits on advisory boards for Novo Nordisk and Sanofi. Drs Gill, Zhou, and Preblick and Mr Li are employees and stockholders of Sanofi. Mr Huse is an employee of Evidera and a contractor for Sanofi. Dr Reid is a speaker and consultant for Novo Nordisk and Sanofi-Aventis and is a consultant for AstraZeneca and Intarcia.

Clinical outcomes in high-hypoglycaemia-risk patients with type 2 diabetes switching to insulin glargine 300U/mL versus a first-generation basal insulin analogue in the United States : Results from the DELIVER High Risk real-world study.

AimsTo compare 12‐month clinical effectiveness of insulin glargine 300 units/mL (Gla‐300) versus first‐generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla‐100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla‐300 or Gla‐100/IDet) in a real‐world setting.MethodsDELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla‐300 (Gla‐300 switchers) and were propensity score‐matched (1:1) to patients who switched to Gla‐100 or IDet (Gla‐100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (<7% and <8%), and incidence and event rates of hypoglycaemia (all‐hypoglycaemia and hypoglycaemia associated with an inpatient/emergency department [ED] contact).ResultsHbA1c reductions were similar following switching to Gla‐300 or Gla‐100/IDet (−0.51% vs. −0.53%; p = .67), and patients showed similar attainment of HbA1c goals. Patients in both cohorts had comparable all‐hypoglycaemia incidence and event rates. However, the Gla‐300 switcher cohort had a significantly lower risk of inpatient/ED‐associated hypoglycaemia (adjusted odds ratio: 0.73, 95% confidence interval: 0.60–0.89; p = .002) and experienced significantly fewer inpatient/ED‐associated hypoglycaemic events (0.21 vs. 0.33 events per patient per year; p < .001).ConclusionIn patients with T2D at high risk of hypoglycaemia, switching to Gla‐300 or Gla‐100/IDet achieved similar HbA1c reductions and glycaemic goal attainment, but Gla‐300 switchers had a significantly lower risk of hypoglycaemia associated with an inpatient/ED contact during 12 months after switching.

Surpassing insulin glargine in type 2 diabetes with tirzepatide

In this centennial year of the isolation and purification of insulin by Banting and colleagues,1 insulin remains a mainstay of treatment for diabetes, being efficacious and cost-effective in controlling glycaemia in people with type 2 diabetes who are poorly controlled on maximal or near-maximal doses of oral hypoglycaemics. The basal analogue insulin glargine is often used as the first-choice injectable for this group, using the algorithm pioneered in the 2003 Treat-to-Target Trial (TTT),2 with progressive titration of insulin doses dependent on measurements of fasting glucose.

Insulin glargine 300 units/mL for the treatment of individuals with type 2 diabetes in the real world: A review of the DELIVER programme.

Evidence from randomized controlled trials (RCTs) has shown that second‐generation basal insulin (BI) analogues, insulin glargine 300 U/mL (Gla‐300) and insulin degludec (IDeg), provide similar glycaemic control, with a lower risk of hypoglycaemia compared with the first‐generation BI analogue insulin glargine 100 U/mL (Gla‐100) in people with type 2 diabetes (T2D). However, the highly selected participants and frequent follow‐up of RCTs may not be truly representative of real‐life clinical practice. It is important to assess the safety and effectiveness of these second‐generation BI analogues in real‐life clinical practice settings. The DELIVER programme utilized electronic healthcare records from the United States to compare clinical outcomes in people with T2D who received either Gla‐300 or other BI analogues in real‐world clinical practice. This review provides a concise overview of the results of the DELIVER studies. Overall, Gla‐300 provided similar antihyperglycaemic effectiveness and a lower risk of hypoglycaemia versus the first‐generation BI analogues Gla‐100 and insulin detemir in people with T2D who had switched BIs. In those who were insulin‐naïve, initiation with Gla‐300 versus Gla‐100 was associated with significantly better antihyperglycaemic effectiveness and similar or lower hypoglycaemic risk. Both glycaemic control and hypoglycaemia risk were also shown to be similar with Gla‐300 and IDeg, in people who had switched BIs and in those who were insulin‐naïve. In addition, the DELIVER 2 study reported that people with T2D who switched to Gla‐300 had reduced healthcare resource utilization, with an overall saving of US$1439 per person per year compared with those who switched to another BI analogue. Overall, the real‐world DELIVER programme showed that the glycaemic control with a low risk of hypoglycaemia observed with Gla‐300 in RCTs was also seen in standard clinical practice.

A cross-sectional study of the quality of life of patients living with type 1 diabetes treated with insulin glargine and neutral protamine Hagedorn insulin and the implications

Abstract Objectives The study aim was to identify key factors associated with the health-related quality of life (HRQOL) of patients with type 1 diabetes mellitus (T1DM) treated with neutral protamine Hagedorn (NPH) insulin or human insulin analog glargine (IGLA). Methods We conducted two cross-sectional studies in Minas Gerais State, Brazil. One with 401 patients treated with IGLA, and the other with 179 T1DM patients treated with NPH. HRQOL was measured by Euroqol (EQ-5D-3L). Key findings Most participants were male (51%), aged between 18 and 40 years (47%), non-black (58%) and from the highest economic strata (A1-B2) (74%). Participants perceived their health as good/very good (51%), had one to three medical consultations in the previous year (51%), were not hospitalized in the previous year (74%), did not report angina (96%), diabetic neuropathy (90%), hearing loss (94%) or kidney disease (89%). Non-severe hypoglycaemia episodes in the last 30 days were reported by 17% of participants. Conclusions Higher HRQOL was associated with younger age (18–40 years), good/very good health self-perception, having had up to three medical consultations in the last year, not being hospitalized in the last year, having none to three comorbidities, not reporting angina, diabetic neuropathy, hearing loss or kidney disease and having had episodes of non-severe hypoglycaemia. In addition, the findings of our study demonstrated inequalities in access to treatment, which will be the subject of future research projects.

Molecular Modeling and Bioinformatics Analysis of Drug-Receptor Interactions in the System Formed by Glargine, Its Metabolite M1, the Insulin Receptor, and the IGF1 Receptor

Introduction:Insulin and insulin-like growth factor type 1 (IGF1) regulate multiple physiological functions by acting on the insulin receptor (IR) and insulin-like growth factor type 1 receptor (IGF1R). The insulin analog glargine differs from insulin in three residues (GlyA21, ArgB31, ArgB32), and it is converted to metabolite M1 (lacks residues ArgB31 and ArgB32) by in vivo processing. It is known that activation of these receptors modulates pathways related to metabolism, cell division, and growth. Though, the structures and structural basis of the glargine interaction with these receptors are not known.Aim:To generate predictive structural models, and to analyze the drug/receptor interactions in the system formed by glargine, its metabolite M1, IR, and IGF1R by using bioinformatics tools.Methods:Ligand/receptor models were built by homology modeling using SWISSMODEL, and surface interactions were analyzed using Discovery Studio® Visualizer. Target and hetero target sequences and appropriate template structures were used for modeling.Results:Our glargine/IR and metabolite M1/IR models showed an overall symmetric T-shaped conformation and full occupancy with four ligand molecules. The glargine/IR model revealed that the glargine residues ArgB31 and ArgB32 fit in a hydrophilic region formed by the α-chain C-terminal helix (αCT) and the cysteine-rich region (CR) domain of this receptor, close to the CR residues Arg270-Arg271-Gln272 and αCT residue Arg717. Regarding IGF1R, homologous ligand/receptor models were further built assuming that the receptor is in a symmetrical T-shaped conformation and is fully occupied with four ligand molecules, similar to what we described for IR. Our glargine/IGF1R model showed the interaction of the glargine residues ArgB31 and ArgB32 with Glu264 and Glu305 in the CR domain of IGF1R.Conclusion:Using bioinformatics tools and predictive modeling, our study provides a better understanding of the glargine/receptor interactions.

The Safety and Efficacy of Second-Generation Basal Insulin Analogues in Adults with Type 2 Diabetes at Risk of Hypoglycemia and Use in Other Special Populations: A Narrative Review.

Hypoglycemia is a major barrier impeding glycemic control in persons with type 2 diabetes mellitus and creates a substantial burden on the healthcare system. Certain populations that require special attention, such as older adults and individuals with renal impairment, a longer duration of diabetes or those who have experienced prior hypoglycemia, may be at a higher risk of hypoglycemia, particularly with insulin treatment. Second-generation basal insulin analogues (insulin glargine 300 U/mL and degludec) have demonstrated reductions in hypoglycemia compared with insulin glargine 100 U/mL although evidence of this benefit across specific populations is less clear. In this review we summarize the literature with respect to the efficacy and safety data for second-generation basal insulin analogues in adults with type 2 diabetes mellitus who are at risk of hypoglycemia or who require special attention. Randomized controlled trials, meta-analyses and real-world evidence demonstrate that the use of second-generation basal insulin analogues is associated with less hypoglycemia compared with insulin glargine 100 U/mL without compromising glycated hemoglobin control. A reduced risk of hypoglycemia with second-generation basal insulin analogues was evident in older adults and in individuals with obesity, renal impairment, a history of cardiovascular disease or a long duration of insulin use. Further studies are needed in other populations, including those with more severe renal impairment or hepatic dysfunction, the hospitalized population and those with cognitive impairment. Overall, less hypoglycemia associated with second-generation basal insulin analogues may help reduce barriers for insulin use, improve adherence and offset the costs of hypoglycemia-related healthcare resource utilization.