Ultra rapid lispro showed greater reduction in postprandial glucose versus Humalog in children, adolescents and adults with type 1 diabetes mellitus.

AIM: This study compared the pharmacokinetics, glucodynamics and tolerability following single subcutaneous doses of ultra rapid lispro (URLi) versus Humalog in children (6-11 years), adolescents (12-17 years) and adults (18-64 years) with type 1 diabetes mellitus (T1D). MATERIALS AND METHODS: The study was a randomized, two-period, subject- and investigator-blind, crossover design in participants with T1D. Participants received a 0.2 U/kg bolus dose immediately before a liquid mixed meal tolerance test. Insulin lispro and glucose concentrations were measured. RESULTS: The study included 13 children, 14 adolescents and 15 adults. Consistently across the age groups, onset of appearance was 4-5 min faster, the early 50% tmax was reduced by 7-13 min, and exposure in the first 15 min was increased by 3.5-6.5-fold following URLi compared with Humalog (all p < .01). Exposure after 3 h was decreased by 37-58% (p = .02) and the duration was reduced by 56 min (p = .006) in children and 36 min (p = .022) in adolescents with URLi compared with Humalog. The maximum and overall exposure were similar between treatments. Postprandial glucose at 1 h was reduced by 42 mg/dl in children (p = .008), 19 mg/dl (p = .195) in adolescents and 34 mg/dl (p = .018) in adults following URLi versus Humalog. The glucose excursion during a 5-h test meal period was reduced by 16% in children and 9% in adolescents compared with Humalog. URLi was well tolerated in all age groups. CONCLUSIONS: URLi showed an accelerated insulin lispro absorption and greater postprandial glucose reduction compared with Humalog in children, adolescents and adults with T1D.

Efficacy and safety of ultra-rapid lispro versus lispro in children and adolescents with type 1 diabetes: The PRONTO-Peds trial.

AIMS: To evaluate the efficacy and safety of ultra-rapid lispro (URLi) versus lispro in a paediatric population with type 1 diabetes (T1D) in a Phase 3, treat-to-target study. MATERIALS AND METHODS: After a 4-week lead-in to optimize basal insulin, participants were randomized to double-blind URLi (n = 280) or lispro (n = 298) injected 0 to 2 minutes prior to meals (mealtime), or open-label URLi (n = 138) injected up to 20 minutes after start of meals (postmeal). Participants remained on pre-study basal insulin (degludec, detemir or glargine). The primary endpoint was glycated haemoglobin (HbA1c) change from baseline after 26 weeks (noninferiority margin 4.4 mmol/mol [0.4%]). RESULTS: Both mealtime and postmeal URLi demonstrated noninferiority to lispro for HbA1c: estimated treatment difference (ETD) for mealtime URLi -0.23 mmol/mol (95% confidence interval [CI] -1.84, 1.39) and postmeal URLi -0.17 mmol/mol (95% CI -2.15, 1.81). Mealtime URLi reduced 1-hour postprandial glucose (PPG) daily mean (P = 0.001) and premeal to 1 hour postmeal PPG excursion daily mean (P < 0.001) versus lispro. The rate and incidence of severe, nocturnal or documented hypoglycaemia (<3.0 mmol/L [54 mg/dL]) were similar for all treatments. With mealtime URLi versus lispro, the rate of postdose hypoglycaemia (<3.0 mmol/L) was higher at ≤2 hours (P = 0.034). The incidence of treatment-emergent adverse events was similar for all treatments. More participants reported an injection site reaction with mealtime URLi (7.9%) versus postmeal URLi (2.9%) and lispro (2.7%). CONCLUSIONS: In children and adolescents with T1D, URLi demonstrated good glycaemic control, and noninferiority to lispro in HbA1c change for mealtime and postmeal URLi. When dosed at the beginning of meals, URLi reduced 1-hour PPG and PPG excursions versus lispro.

Lilly Insulin Glargine Versus Lantus® in Insulin-Naïve and Insulin-Treated Adults with Type 2 Diabetes: A Randomized, Controlled Trial (ELEMENT 5).

INTRODUCTION: This study compared the efficacy and safety of similar U-100 insulin glargine products, namely, Lilly insulin glargine (LY IGlar; Basaglar®) and the reference insulin glargine product (IGlar; Lantus®), used once daily in combination with oral antihyperglycemic medications (OAMs) in adults with type 2 diabetes (T2D). METHODS: ELEMENT 5 was a phase III, randomized, multinational, open-label, treat-to-target, 24-week trial. Participants were insulin naïve (glycated hemoglobin [HbA1c] ≥ 7.0% to ≤ 11.0%) or on basal insulin (IGlar, neutral protamine Hagedorn or insulin detemir; HbA1c ≤ 11.0%) and taking ≥ 2 OAMs. The primary objective was to show  that LY IGlar is noninferior to IGlar in terms of HbA1c reduction (0.4% noninferiority margin). RESULTS: The study population (N = 493) was predominantly Asian (48%) or White (46%), with similar baseline characteristics between arms (P > 0.05). At 24 weeks, LY IGlar was noninferior to IGlar in terms of change in HbA1c level from baseline (- 1.25 vs. - 1.22%, respectively; least squares mean difference - 0.04%; 95% confidence interval - 0.22%, 0.15%). Other 24-week efficacy and safety results were also similar between treatments (P > 0.05), including insulin dose; percentage of patients having HbA1c of < 7% and ≤ 6.5%; overall rate and incidence of total, nocturnal, and severe hypoglycemia; adverse events; insulin antibody response; and weight gain. Daily mean 7-point self-monitored blood glucose reduction was similar between treatments at 24 weeks, with no differences at any time point except premorning-meal (fasting) blood glucose (LY IGlar - 2.37 mmol/L; IGlar - 2.69 mmol/L; P = 0.007). CONCLUSION: Overall, LY IGlar and IGlar combined with OAMs provided similar glucose control and safety findings in this T2D population, which included a greater proportion of Asian patients and had broader background basal insulin experience than a previously studied T2D population. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02302716. FUNDING: Eli Lilly and Company and Boehringer Ingelheim. Plain language summary available for this article.

Similar Efficacy and Safety of Basaglar® and Lantus® in Patients with Type 2 Diabetes in Age Groups (< 65 Years, ≥ 65 Years): A Post Hoc Analysis from the ELEMENT-2 Study.

INTRODUCTION: To compare efficacy and safety of Basaglar® [insulin glargine 100 units/mL; LY insulin glargine (LY IGlar)] to Lantus® [insulin glargine 100 units/mL; SA insulin glargine (SA IGlar)] in older (≥ 65 years) or younger (< 65 years) patients with type 2 diabetes (T2D). METHODS: This subgroup analysis of a phase 3, randomized, double-blind, multinational, 24-week study compared LY IGlar and SA IGlar on several clinical efficacy (change in glycated hemoglobin (A1c), basal insulin dose, weight) and safety outcomes (incidence of adverse events, insulin antibodies, hypoglycemia incidence and rates) in patients either ≥ 65 or < 65 years. RESULTS: Compared with patients aged < 65 years (N = 542), patients aged ≥ 65 years (N = 214) had a significantly longer duration of diabetes; lower baseline A1c and body weight; and body mass index; and were more likely to report prestudy SA IGlar use. Compared to patients < 65 years, patients ≥ 65 years needed a lower basal insulin dose and experienced lower body weight gain. There were no significant treatment-by-age interactions for the clinical efficacy and safety outcomes, indicating that there was no differential treatment effect (LY IGlar vs SA IGlar) for patients ≥ 65 years vs those < 65 years. Moreover, within each age subgroup, LY IGlar and SA IGlar were similar for all clinical efficacy and safety outcomes. CONCLUSIONS: LY IGlar and SA IGlar exhibit similar efficacy and safety in patients with T2D who are ≥ 65 years and in those < 65 years. TRIAL REGISTRATION: ClinicalTrials.gov trial registration: NCT01421459. FUNDING: Eli Lilly and Company and Boehringer-Ingelheim.

Plain language summary available for this article.The aim of this phase 3 clinical study was to compare the efficacy and safety of two drugs, Basaglar^® (LY IGlar) and Lantus (SA IGlar), in patients with type 2 diabetes that were either 65 years of age and/or older or younger than 65 years of age. This study ran for 24 weeks. The factors used to measure efficacy were changes in glycated hemoglobin (A1c), insulin dose, and weight. The safety outcomes were incidence of adverse events, incidence and levels of insulin antibodies, and the incidence and rate of low blood sugar. Compared with patients less than 65 years of age (N = 542), patients 65 years of age and older (N = 214) had diabetes for a significantly longer time period; had a lower baseline A1c, body weight, and body mass index; and were more likely to report that they used SA IGlar prestudy. Compared to patients less than 65 years of age, patients equal to or older than 65 years of age showed significantly smaller increases in insulin dose and body weight. There were no significant treatment-by-age interactions for the efficacy and safety outcomes, indicating that there was no difference in treatment effect (LY IGlar vs SA IGlar) for patients equal to or older than 65 years of age vs those less than 65 years of age. Moreover, within each age subgroup, LY IGlar and SA IGlar were similar for all clinical efficacy and safety outcomes. LY IGlar and SA IGlar have similar efficacy and safety in patients with T2D who are equal to or older than 65 years of age and in those less than 65 years of age.

Clinical Outcomes of Patients with Diabetes Who Exhibit Upper-Quartile Insulin Antibody Responses After Treatment with LY2963016 or Lantus® Insulin Glargine.

INTRODUCTION: We compared insulin antibody response (IAR) profiles in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) who received LY2963016 insulin glargine (LY IGlar) or Lantus® insulin glargine (IGlar) and evaluated the potential relationship between higher IARs and clinical and safety outcomes with a focus on patients who exhibited antibody responses in the upper quartile. METHODS: Data from ELEMENT-1 (52-week open-label in T1D) and ELEMENT-2 (24-week, double-blind study in T2D) were analyzed. Maximum postbaseline IAR levels and proportions of patients in the upper quartile of maximum antibody percent binding (UQMAPB; patients with maximum postbaseline percent binding in the highest 25% of maximum values observed) were compared for differential treatment effects on clinical efficacy outcomes and incidence of adverse events. Continuous outcomes were analyzed by analysis of covariance. Categorical data were analyzed by the Cochran-Mantel-Haenszel or Breslow-Day test. RESULTS: In both studies (N = 532 evaluable patients with T1D; N = 730 with T2D), no statistically significant differences between LY IGlar and IGlar were observed for maximum antibody percent binding (MAPB) levels or for proportions of patients in the respective UQMAPB. No statistically significant differential treatment effects were observed in the relationship between MAPB and clinical efficacy and safety outcomes. CONCLUSIONS: Maximum postbaseline IAR levels and the proportion of patients with high IAR levels were similar for LY IGlar and IGlar. High antibody levels did not affect clinical outcomes. These results add further evidence supporting similar IARs of LY IGlar and IGlar. FUNDING: Eli Lilly and Company and Boehringer-Ingelheim.

Utilization of a multidisciplinary team for inpatient diabetes care.

Diabetes is often noted as a secondary diagnosis when patients are admitted to the hospital for care. Patients admitted to critical care areas are usually more ill and require aggressive glucose control. Often the education and self-care management skills needed for home management are overlooked until discharge, which can cause an increased length of stay. There is a feeling of frustration among nurses who are unable to adequately meet the needs of these patients and their families. In one community hospital setting, they have designed a model that identifies patient needs on admission and utilizes a multidisciplinary team. Beginning the "discharge" process early in the admission will ensure that a timely discharge with a well-trained patient will occur.