RESUMEN
Aim: To evaluate the efficacy and safety of URLi (ultra rapid lispro insulin) compared to insulin lispro as bolus insulin with basal insulin using CGM in the individuals with type 2 diabetes(T2D) in China. Methods: This was a double-blind, randomized, parallel, prospective, phase 3 study. Subjects with uncontrolled T2D were recruited and randomized 1:2 into the insulin lispro and URLi groups. Subjects received a consistent basal insulin regimen during the study and self-administered insulin lispro or URLi before each meal throughout the treatment period. Subjects underwent a 3-day continuous glucose monitoring (CGM) at the baseline and endpoint respectively, and then CGM data were analyzed. The primary endpoint was to compare the difference in postprandial glucose (PPG) control using CGM between the two groups. Results: A total of 57 subjects with T2D completed the study. Our CGM data showed that postprandial glucose excursions after breakfast (BPPGE) in the URLi group was lower than that in the insulin lispro group (1.59 ± 1.57 mmol/L vs 2.51 ± 1.73 mmol/L, p = 0.046). 1-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.37 ± 3.28 mmol/L vs 0.24 ± 2.58 mmol/L, p = 0.047). 2-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.12 ± 4.00 mmol/L vs 1.22 ± 2.90 mmol/L, p = 0.021). The mean HbA1c level decreased by 1.1% in the URLi group and 0.99% in the insulin lispro group, with no treatment difference (p = 0.642). In the CGM profile, TBR was not significantly different between the two groups (p = 0.743). The weight gain also did not differ between the two groups (p = 0.303). Conclusion: URLi can control breakfast PPG better than insulin lispro in adults with T2D in China, while it is non-inferior in improving HbA1c. The incidence of hypoglycemic and weight gain were similar between the two groups.
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Automonitorización de la Glucosa Sanguínea , Glucemia , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Insulina Lispro , Periodo Posprandial , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Insulina Lispro/uso terapéutico , Insulina Lispro/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Glucemia/análisis , China/epidemiología , Método Doble Ciego , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Automonitorización de la Glucosa Sanguínea/métodos , Estudios Prospectivos , Control Glucémico/métodos , Adulto , Anciano , Hemoglobina Glucada/análisis , Quimioterapia CombinadaRESUMEN
Objective: To evaluate postprandial glucose control when applying (1) faster-acting insulin aspart (Fiasp) compared to insulin aspart and (2) ultra-rapid insulin lispro (Lyumjev) compared to insulin lispro using the CamAPS FX hybrid closed-loop algorithm. Research Design and Methods: We undertook a secondary analysis of postprandial glucose excursions from two double-blind, randomized, crossover hybrid closed-loop studies contrasting Fiasp to standard insulin aspart, and Lyumjev to standard insulin lispro. Endpoints included incremental area under curve (iAUC)-2h, iAUC-4h, 4 h postprandial time in target range, time above range, and time below range. It was approved by independent research ethics committees. Results: Two trials with 8 weeks of data from 51 adults with type 1 diabetes were analyzed and 7137 eligible meals were included. During Lyumjev compared with insulin lispro, iAUC-2h and iAUC-4h were significantly decreased following breakfast (mean difference 92 mmol/L per 2 h (95% confidence interval [CI]: 56 to 127); P < 0.001 and 151 mmol/L per 4 h (95% CI: 74 to 229); P < 0.001, respectively) and the evening meal (P < 0.001 and P = 0.011, respectively). Mean time in target range (3.9-10.0 mmol/L) for 4 h postprandially significantly increased during Lyumjev with a mean difference of 6.7 percentage points (95% CI: 3.3 to 10) and 5.7 percentage points (95% CI: 1.4 to 9.9) for breakfast and evening meal, respectively. In contrast, there were no significant differences in iAUC-2h, iAUC-4h, and the other measures of postprandial glucose control between insulin aspart and Fiasp during breakfast, lunch, and evening meal (P > 0.05). Conclusion: The use of Lyumjev with CamAPS FX closed-loop system improved postprandial glucose excursions compared with insulin lispro, while the use of Fiasp did not provide any advantage compared with insulin aspart. Clinical Trial Registration numbers: NCT04055480, NCT05257460.
Asunto(s)
Glucemia , Estudios Cruzados , Diabetes Mellitus Tipo 1 , Hipoglucemiantes , Insulina Aspart , Insulina Lispro , Periodo Posprandial , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Adulto , Masculino , Femenino , Insulina Lispro/uso terapéutico , Insulina Lispro/administración & dosificación , Glucemia/análisis , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Insulina Aspart/uso terapéutico , Insulina Aspart/administración & dosificación , Método Doble Ciego , Persona de Mediana Edad , Sistemas de Infusión de Insulina , AlgoritmosRESUMEN
Importance: Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety of adding tirzepatide vs prandial insulin to treatment in patients with inadequate glycemic control with basal insulin have not been described. Objective: To assess the efficacy and safety of tirzepatide vs insulin lispro as an adjunctive therapy to insulin glargine. Design, Setting, and Participants: This open-label, phase 3b clinical trial was conducted at 135 sites in 15 countries (participants enrolled from October 19, 2020, to November 1, 2022) in 1428 adults with type 2 diabetes taking basal insulin. Interventions: Participants were randomized (in a 1:1:1:3 ratio) to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708). Main Outcomes and Measures: Outcomes included noninferiority of tirzepatide (pooled cohort) vs insulin lispro, both in addition to insulin glargine, in HbA1c change from baseline at week 52 (noninferiority margin, 0.3%). Key secondary end points included change in body weight and percentage of participants achieving hemoglobin A1c (HbA1c) target of less than 7.0%. Results: Among 1428 randomized participants (824 [57.7%] women; mean [SD] age, 58.8 [9.7] years; mean [SD] HbA1c, 8.8% [1.0%]), 1304 (91.3%) completed the trial. At week 52, estimated mean change from baseline in HbA1c with tirzepatide (pooled cohort) was -2.1% vs -1.1% with insulin lispro, resulting in mean HbA1c levels of 6.7% vs 7.7% (estimated treatment difference, -0.98% [95% CI, -1.17% to -0.79%]; P < .001); results met noninferiority criteria and statistical superiority was achieved. Estimated mean change from baseline in body weight was -9.0 kg with tirzepatide and 3.2 kg with insulin lispro (estimated treatment difference, -12.2 kg [95% CI, -13.4 to -10.9]). The percentage of participants reaching HbA1c less than 7.0% was 68% (483 of 716) with tirzepatide and 36% (256 of 708) with insulin lispro (odds ratio, 4.2 [95% CI, 3.2-5.5]). The most common adverse events with tirzepatide were mild to moderate gastrointestinal symptoms (nausea: 14%-26%; diarrhea: 11%-15%; vomiting: 5%-13%). Hypoglycemia event rates (blood glucose level <54 mg/dL or severe hypoglycemia) were 0.4 events per patient-year with tirzepatide (pooled) and 4.4 events per patient-year with insulin lispro. Conclusions and Relevance: In people with inadequately controlled type 2 diabetes treated with basal insulin, weekly tirzepatide compared with prandial insulin as an additional treatment with insulin glargine demonstrated reductions in HbA1c and body weight with less hypoglycemia. Trial Registration: ClinicalTrials.gov Identifier: NCT04537923.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Insulina Glargina , Insulina Lispro , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucemia/análisis , Peso Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/análisis , Hipoglucemia/inducido químicamente , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina/uso terapéutico , Insulina Glargina/administración & dosificación , Insulina Glargina/efectos adversos , Insulina Glargina/uso terapéutico , Insulina Lispro/administración & dosificación , Insulina Lispro/efectos adversos , Insulina Lispro/uso terapéutico , Resultado del Tratamiento , Internacionalidad , AncianoRESUMEN
BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).
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Diabetes Mellitus Tipo 1 , Hipoglucemiantes , Insulina Aspart , Sistemas de Infusión de Insulina , Insulina Lispro , Adolescente , Adulto , Anciano , Biónica/instrumentación , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea/instrumentación , Automonitorización de la Glucosa Sanguínea/métodos , Niño , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina/uso terapéutico , Insulina Aspart/administración & dosificación , Insulina Aspart/efectos adversos , Insulina Aspart/uso terapéutico , Sistemas de Infusión de Insulina/efectos adversos , Insulina Lispro/administración & dosificación , Insulina Lispro/efectos adversos , Insulina Lispro/uso terapéutico , Persona de Mediana Edad , Adulto JovenRESUMEN
Background: Ultra rapid lispro (URLi) is a new insulin lispro formulation that has accelerated absorption and improved postprandial glucose control compared with insulin lispro (Humalog®). The compatibility and safety of URLi versus lispro were evaluated in patients with type 1 diabetes using continuous subcutaneous insulin infusion (insulin pump). Methods: In this phase 3, double-blind, crossover study, 49 patients were randomized to two 6-week treatment periods, after a 2-week lead-in period on lispro. The primary endpoint was the rate of infusion set failures due to a pump occlusion alarm, or unexplained hyperglycemia with blood glucose >13.9 mmol/L (250 mg/dL) that did not decrease within 1 h after a correction bolus. Results: There was no significant difference in the rate of infusion set failures between URLi and lispro (0.03 vs. 0.05 events/30 days, P = 0.375). A higher rate of premature infusion set changes was observed with URLi (1.13 vs. 0.78 events/30 days; P = 0.028), translating to one additional infusion set change approximately every 3 months. A trend toward improved glycemic control was observed with URLi treatment: Time in range 3.9-10.0 mmol/L (71-180 mg/dL) was 65.7% ± 1.3% versus 63.0% ± 1.3%. Treatment-emergent adverse events (TEAEs) were reported by 46.9% of patients on URLi treatment and 18.8% on lispro. This difference was driven by an increase in infusion site reactions-more than 90% were mild. Incidence of all other TEAEs and severe hypoglycemia was similar between treatments. Conclusions: URLi was compatible with insulin pump use with a safety profile similar to lispro.
Asunto(s)
Diabetes Mellitus Tipo 1 , Sistemas de Infusión de Insulina , Insulina Lispro , Glucemia , Estudios Cruzados , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina Lispro/administración & dosificación , Insulina Lispro/efectos adversosRESUMEN
OBJECTIVE: To understand physicians' reasons for prescribing Insulin Lispro 200 units/ml (IL200) and their experience with IL200 treatment in Germany. METHODS: The survey consisted of 28 questions on physician's profile, average IL200 patients' characteristics and rationales for prescribing IL200. Questions were rated on a scale of 0 ('not at all important'/'strongly disagree') to 4 ('absolutely important'/'strongly agree'). RESULTS: The surveyed physicians had a mean (SD) experience of 18.1 (7.0) years managing diabetes, consulted an average of 226.8 patients with diabetes/month and prescribed IL200 to 56.1% of their patients on mealtime insulin (MTI). About 80.0% of IL200 patients had type 2 diabetes mellitus, were overweight/obese, and received >20 units/day of MTI. More than 70.0% of physicians rated patient's insulin dose, pattern of self-measured glucose levels, hemoglobin A1c (HbA1c) (clinical); adherence, hypoglycemia knowledge, motivation to improve lifestyle, desire to reduce injection volume and emotional struggle with controlling HbA1c (behavioral) as 'very important'/'absolutely important' factors when prescribing IL200. CONCLUSION: Physicians considered IL200 a promising treatment option that reduces the injection burden for patients on MTI. Physicians adopted a patient-centered perspective by aligning IL200 prescribing decisions with each patient's medical needs and non-clinical preferences, with an aim to encourage treatment adherence through resorting to IL200's advantageous attributes.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Hipoglucemiantes/uso terapéutico , Insulina Lispro/uso terapéutico , Sobrepeso/epidemiología , Médicos/psicología , Adulto , Glucemia , Automonitorización de la Glucosa Sanguínea , Estudios Transversales , Femenino , Hemoglobina Glucada , Conocimientos, Actitudes y Práctica en Salud , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina Lispro/administración & dosificación , Insulina Lispro/efectos adversos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Motivación , Obesidad/epidemiología , Periodo Posprandial , Pautas de la Práctica en MedicinaRESUMEN
PURPOSE: Ultra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This study compared the pharmacokinetic and glucodynamic parameters of URLi and Lispro (Humalog®) at 3 dose levels in healthy subjects. METHODS: This randomized, 6-period, subject- and investigator-blind, crossover study included 42 healthy subjects. At each period, subjects received a single subcutaneous dose of 7, 15, or 30 U of URLi or Lispro followed by a 10-h automated euglycemic clamp. Insulin lispro and blood glucose concentrations were measured. FINDINGS: Across all 3 doses, insulin lispro appeared in the serum 2-5 min faster, and exposure was 6- to 8-fold greater in the first 15 min, with URLi versus Lispro. Exposure beyond 3 h postdose was 45%-52% lower, and duration of exposure was 67-86 min shorter with URLi versus Lispro for all dose levels. Onset of insulin action was 7-9 min faster and insulin action was ~3-fold greater in the first 30 min with URLi versus Lispro across the dose levels. Insulin action beyond 4 h was reduced by 32%-45%, and duration of action was reduced by 47-67 min, with URLi versus Lispro for all 3 dose levels. Overall exposure and total glucose infused were similar between URLi and Lispro at each dose level. Dose proportionality was observed for maximum and overall exposure after URLi. Less than dose-proportional increases in maximum and total glucose infused were observed and were similar for both URLi and Lispro. IMPLICATIONS: URLi exhibited ultra-rapid pharmacokinetic and glucodynamic parameters across all 3 dose levels studied and exhibited dose-proportional increases in exposure in healthy subjects. ClinicalTrials.gov identifier: NCT03286751.
Asunto(s)
Glucemia/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Insulina Lispro/administración & dosificación , Adolescente , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Glucosa/administración & dosificación , Técnica de Clampeo de la Glucosa , Humanos , Insulina Lispro/farmacocinética , Masculino , Persona de Mediana Edad , Periodo Posprandial , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro in patients with type 2 diabetes on a basal-bolus insulin regimen. RESEARCH DESIGN AND METHODS: This was a phase 3, treat-to-target, double-blind 26-week study. After an 8-week lead-in to optimize basal insulin glargine or degludec in combination with prandial lispro treatment, patients were randomized to blinded URLi (n = 336) or lispro (n = 337) injected 0-2 min prior to meals. Patients could continue metformin and/or a sodium-glucose cotransporter 2 inhibitor. The primary end point was change in HbA1c from baseline to 26 weeks (noninferiority margin 0.4%), with multiplicity-adjusted objectives for postprandial glucose (PPG) excursions during a standardized meal test. RESULTS: HbA1c improved for both URLi and lispro, and noninferiority was confirmed: estimated treatment difference (ETD) 0.06% (95% CI -0.05; 0.16). Mean change in HbA1c was -0.38% for URLi and -0.43% for lispro, with an end-of-treatment HbA1c of 6.92% and 6.86%, respectively. URLi was superior to lispro in controlling 1- and 2-h PPG excursions: 1-h ETD, -0.66 mmol/L (95% CI -1.01, -0.30); 2-h ETD, -0.96 mmol/L (-1.41, -0.52). Significantly lower PPG excursions were evident from 0.5 to 4.0 h postmeal with URLi treatment. There were no significant treatment differences in rates of severe or documented hypoglycemia (<3.0 mmol/L). Incidence of overall treatment-emergent adverse events was similar between treatments. CONCLUSIONS: URLi compared with lispro in a basal-bolus regimen was confirmed to be noninferior for HbA1c and superior to lispro for PPG control in patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina Glargina/administración & dosificación , Insulina Lispro/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Anciano , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/metabolismo , Método Doble Ciego , Quimioterapia Combinada , Estudios de Equivalencia como Asunto , Femenino , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina Glargina/efectos adversos , Insulina Lispro/efectos adversos , Insulina de Acción Prolongada/efectos adversos , Masculino , Comidas , Metformina/administración & dosificación , Metformina/efectos adversos , Persona de Mediana Edad , Periodo Posprandial/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: The 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 METHODS: In 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). RESULTS: Mean ± 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%). CONCLUSIONS: A 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.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Control Glucémico/métodos , Insulina/administración & dosificación , Adulto , Anciano , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/efectos adversos , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Insulina Glargina/administración & dosificación , Insulina Lispro/administración & dosificación , Masculino , Comidas , Persona de Mediana Edad , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
In China, most normal BMI (body mass index of ≥18.5 to <25 kg/m2) adults with type 2 diabetes (T2DM) exhibit visceral adiposity. This study compared the effects of exenatide and humalog Mix25 on normal BMI patients with T2DM and visceral adiposity. A total of 95 patients were randomized to receive either exenatide or humalog Mix25 treatment for 24 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were quantified by magnetic resonance imaging (MRI) and liver fat content (LFC) by liver proton magnetic resonance spectroscopy (1H MRS). Each patient's weight, waist circumference, BMI, blood glucose, insulin sensitivity, pancreatic ß-cell function, and fibroblast growth factor 21 (FGF-21) levels were measured. Data from 81 patients who completed the study (40 and 41 in the exenatide and humalog Mix25 groups, respectively) were analysed. The change in 2 h plasma blood glucose was greater in the exenatide group (P = 0.039). HOMA-IR and MBCI improved significantly after exenatide therapy (P < 0.01, P = 0.045). VAT and LFC decreased in both groups (P < 0.01 for all) but to a greater extent in the exenatide group, while SAT only decreased with exenatide therapy (P < 0.01). FGF-21 levels declined more in the exenatide group (P < 0.01), but were positively correlated with VAT in the entire cohort before (r = 0.244, P = 0.043) and after (r = 0.290, P = 0.016) the intervention. The effects of exenatide on glycaemic metabolism, insulin resistance, pancreatic ß-cell function, and fat deposition support its administration to normal BMI patients with T2DM and visceral adiposity.
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Insulinas Bifásicas/farmacología , Distribución de la Grasa Corporal , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida/farmacología , Insulina Lispro/farmacología , Resistencia a la Insulina , Insulina Isófana/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Obesidad Abdominal/tratamiento farmacológico , Adiposidad/efectos de los fármacos , Adiposidad/fisiología , Adulto , Anciano , Insulinas Bifásicas/administración & dosificación , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Exenatida/administración & dosificación , Femenino , Humanos , Insulina Lispro/administración & dosificación , Insulina Isófana/administración & dosificación , Células Secretoras de Insulina/fisiología , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Masculino , Persona de Mediana Edad , Obesidad Abdominal/complicaciones , Obesidad Abdominal/metabolismo , Resultado del TratamientoRESUMEN
Human insulin and its synthetic analogs are considered as life-saving drugs for people suffering from diabetes mellitus. Next to the therapeutic use, scientific and non-scientific literature (e.g. bodybuilding forums; antidoping intelligence and investigation reports) indicate that these prohibited substances are used as performance enhancing agents. In the present report, the development and validation of a sensitive analytical strategy is described for the urinary detection of three rapid-acting insulin analogs (Lispro, Aspart, Glulisine). The method is based on sample purification by the combination of ultrafiltration and immunoaffinity purification and subsequent analysis by nano-flow liquid chromatography coupled to high resolution mass spectrometry. Next to the results on different validation parameters (LOD: 10 pg/mL; recovery: 25-48%; matrix effect: -3-(-8) %), data on urinary elimination times, which were obtained in the frame of an administration study with the participation of healthy volunteers, are presented. The determined detection windows (~9 hours) are expected to help to evaluate current routine analytical methods and aim to aid doping authorities to set appropriate target windows for efficient testing.
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Insulina Aspart/orina , Insulina Lispro/orina , Insulina de Acción Corta/orina , Insulina/análogos & derivados , Detección de Abuso de Sustancias/métodos , Cromatografía Liquida/métodos , Cromatografía Liquida/normas , Voluntarios Sanos , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/orina , Inyecciones Subcutáneas , Insulina/administración & dosificación , Insulina/orina , Insulina Aspart/administración & dosificación , Insulina Lispro/administración & dosificación , Insulina de Acción Corta/administración & dosificación , Espectrometría de Masas/métodos , Espectrometría de Masas/normas , Detección de Abuso de Sustancias/normasRESUMEN
A 38-year-old woman with type 1 diabetes, whose fasting plasma glucose levels were >500 mg/dL under 176 U/day of subcutaneous insulin injection, was admitted to Nippon Medical School Hospital, Tokyo, Japan. When insulin was administered intravenously, she was able to maintain favorable glycemic control even under 24 U/day of regular insulin, showing that she was accompanied by subcutaneous insulin resistance. To choose an optimal insulin regimen, we carried out subcutaneous insulin challenge tests without or with heparin mixture, and found a cocktail of insulin lispro and heparin could reduce blood glucose levels markedly. As a consequence, she achieved favorable blood glucose control by continuous subcutaneous insulin infusion of the cocktail. In summary, the insulin and heparin challenge tests are useful for choosing an optimal insulin regimen in cases of subcutaneous insulin resistance.
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Glucemia/análisis , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Heparina/administración & dosificación , Hipoglucemiantes/administración & dosificación , Sistemas de Infusión de Insulina/normas , Insulina Lispro/administración & dosificación , Resistencia a la Insulina , Adulto , Diabetes Mellitus Tipo 1/patología , Femenino , Humanos , Inyecciones Subcutáneas , PronósticoAsunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Control Glucémico , Hipoglucemiantes/administración & dosificación , Sistemas de Infusión de Insulina , Páncreas Artificial , Embarazo en Diabéticas , Adulto , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Femenino , Humanos , Insulina Glargina/administración & dosificación , Insulina Lispro/administración & dosificación , Nacimiento Vivo , Monitoreo Ambulatorio , Embarazo , Resultado del Embarazo , Calidad de Vida , Factores de Tiempo , Resultado del TratamientoRESUMEN
Inpatient diabetes management of those on hemodialysis poses a major challenge. In a post hoc analysis of a randomized controlled clinical trial, we compared the efficacy of fully automated closed-loop insulin delivery vs. usual care in patients undergoing hemodialysis while in hospital. Compared to control patients receiving conventional subcutaneous insulin therapy, those patients receiving closed-loop insulin delivery significantly increased the proportion of time when a continuous glucose monitor was in the target range of 5.6-10.0 mmol/l by 37.6 percent without increasing the risk of hypoglycemia. Thus, closed-loop insulin delivery offers a novel way to achieve effective and safe glucose control in this vulnerable patient population.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Sistemas de Infusión de Insulina , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Quimioterapia Asistida por Computador/instrumentación , Quimioterapia Asistida por Computador/métodos , Femenino , Hospitalización , Humanos , Bombas de Infusión Implantables , Insulina Aspart/administración & dosificación , Insulina Lispro/administración & dosificación , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Resultado del TratamientoRESUMEN
AIMS: Insulin-treated patients with type 2 diabetes (T2D) and obesity are challenged in achieving body weight stability or reduction, in addition to glycaemic control. Post-hoc analyses of body weight and insulin dose data from the AWARD-4 trial involved comparison of treatment with once-weekly dulaglutide 1.5 mg (N = 295) or 0.75 mg (N = 293) and treatment with daily insulin glargine (N = 296), each with prandial insulin lispro (± metformin). MATERIALS AND METHODS: Changes in weight and in the proportion of patients without weight gain or with weight loss of at least 3%, 5% or 10% or composites of HbA1c less than 7% without weight gain and weight loss of at least 3% after 52 weeks were compared between the dulaglutide (either dose) groups and the insulin glargine group, overall and by baseline BMI (<30, 30-<35, ≥35 kg/m2 ), using analysis of covariance and logistic regression, including interaction terms. RESULTS: The following parameters were statistically significant (P < 0.01) in favour of the dulaglutide-treated groups, at lower mean total daily insulin doses, vs the insulin glargine group. The achieved targets were more pronounced with dulaglutide 1.5 mg than with insulin glargine: LSM weight change difference, -3.23 kg; proportion of patients without weight gain, 49.0% vs 19.0%; proportion of patients with weight loss ≥3%, 21.7% vs 5.7% or with weight loss ≥5%, 10.5% vs 2.4%; proportion of patients with HbA1c <7% without weight gain, 26.2% vs 7.9%; proportion of patients with HbA1c <7% and weight loss ≥3%, 11.9% vs 1.4%, respectively. Treatment effect for these parameters was not significantly different across BMI categories. CONCLUSIONS: Larger proportions of patients in late-stage T2D needing treatment intensification achieved glycemic control without weight gain or with weight loss at lower insulin doses with once-weekly dulaglutide plus daily prandial insulin than with a basal-bolus insulin regimen, overall and across all three BMI subgroups.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Insulina Glargina , Insulina Lispro , Proteínas Recombinantes de Fusión , Pérdida de Peso/efectos de los fármacos , Anciano , Índice de Masa Corporal , Método Doble Ciego , Femenino , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/farmacología , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Insulina Glargina/administración & dosificación , Insulina Glargina/farmacología , Insulina Glargina/uso terapéutico , Insulina Lispro/administración & dosificación , Insulina Lispro/farmacología , Insulina Lispro/uso terapéutico , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/uso terapéuticoRESUMEN
BACKGROUND: This study assessed subcutaneous absorption kinetics of rapid-acting insulin administered as a bolus using bolus delivery speeds commonly employed in commercially available insulin pumps (i.e., 2 and 40 s for delivering 1 insulin unit). MATERIALS AND METHODS: Twenty C-peptide-negative type 1 diabetic subjects were studied on two occasions, separated by at least 7 days, using the euglycemic clamp procedure. After an overnight fast, subjects were given, in random order, a subcutaneous insulin bolus (15 U of insulin lispro, Eli Lilly) either for 30 s using an Animas IR2020 pump (fast bolus delivery) or for 10 min using a Medtronic Minimed Paradigm 512 pump (slow bolus delivery). RESULTS: Fast bolus delivery resulted in an earlier onset of insulin action as compared with slow bolus delivery (21.0 ± 2.5 vs. 34.3 ± 2.7 min; P < 0.002). Furthermore, time to reach maximum insulin effect was found to be 27 min earlier with fast bolus delivery as compared with slow bolus delivery (98 ± 11 vs. 125 ± 16 min; P < 0.005). In addition, the area under the plasma insulin curve from 0 to 60 min for fast bolus delivery was greater than the one for slow bolus delivery (10,307 ± 1291 vs. 8192 ± 865 min·pmol/L; P = 0.027). CONCLUSIONS: Results suggest that insulin bolus delivery with fast delivery speed may result in more rapid insulin absorption and, thus, may provide a better control of meal-related glucose excursions than that obtained with bolus delivery using slow delivery speeds. Our findings may have important implications for the future design of the bolus delivery unit of insulin pumps.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Sistemas de Infusión de Insulina , Insulina Lispro/administración & dosificación , Absorción Subcutánea/efectos de los fármacos , Adolescente , Adulto , Glucemia/efectos de los fármacos , Estudios Cruzados , Diabetes Mellitus Tipo 1/sangre , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Tejido Subcutáneo/efectos de los fármacos , Adulto JovenRESUMEN
We investigated the pharmacodynamics (PD) and pharmacokinetics (PK) of BioChaperone insulin Lispro (BCLIS), faster insulin aspart (FIA) and insulin aspart (ASP) in patients with type 1 diabetes using an insulin pump. In this randomized, double-blind, three-way crossover glucose clamp study, 43 patients received a bolus dose of each insulin (0.15 U/kg) in addition to a basal rate (0.01 U/kg/h), delivered via an insulin pump. With BCLIS, the AUC-GIR,0-60 minutes (primary endpoint) was improved compared to ASP (least square means ratio, 1.63; 95% CI, 1.44-1.88; P < 0.0001) and was similar compared to FIA (least square means ratio, 1.06; 95% CI, 0.94-1.18; P = 0.4609). BCLIS showed faster-on PD (tearly0.5GIRmax ) than ASP and faster-off PD (tlate0.5GIRmax ) than both FIA and ASP. BCLIS also demonstrated significantly higher early exposure (AUCins, 0-60 minutes) and lower late exposure (AUCins,120-600 minutes) than both other insulins. In patients with type 1 diabetes using an insulin pump, BCLIS better mimics prandial insulin secretion and action than ASP and shows a faster off-PD than FIA.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/farmacocinética , Insulina Aspart/farmacocinética , Insulina Lispro/farmacocinética , Adulto , Glucemia/metabolismo , Estudios Cruzados , Diabetes Mellitus Tipo 1/metabolismo , Formas de Dosificación , Método Doble Ciego , Excipientes/farmacocinética , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hipoglucemiantes/administración & dosificación , Infusiones Subcutáneas , Insulina Aspart/administración & dosificación , Sistemas de Infusión de Insulina , Insulina Lispro/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
New concentrated insulins (exceeding 100 units/mL) and dedicated devices have recently become available, offering new treatment options for people with diabetes, for basal and prandial insulin supplementation. The concentrated insulin formulations range from 2-fold concentration (insulin lispro 200 units/mL) with rapid-acting prandial action to 5-fold concentration (human regular insulin, 500 units/mL) with basal and short-acting prandial actions. Long-acting basal insulins include degludec 200 units/mL and glargine 300 units/mL. Concentrated insulins have been developed with the goal of easing insulin therapy by reducing the volume and number of injections and in some cases making use of altered pharmacokinetic and pharmacodynamic properties. This review summarizes the unique characteristics of each concentrated insulin to help healthcare providers and people with diabetes understand how to best use them.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Composición de Medicamentos , Hipoglucemiantes/administración & dosificación , Insulinas/administración & dosificación , Diabetes Mellitus Tipo 2/sangre , Relación Dosis-Respuesta a Droga , Composición de Medicamentos/métodos , Quimioterapia Combinada , Humanos , Hipoglucemiantes/clasificación , Insulina Glargina/administración & dosificación , Insulina Lispro/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Insulina Regular Humana/administración & dosificación , Insulinas/clasificaciónRESUMEN
OBJECTIVE: This study aimed to explore the effects of ambient temperature and relative humidity on insulin pharmacodynamics in adults with type 1 diabetes. MATERIALS AND METHODS: A three-way, cross-over, randomised study was performed in adults with type 1 diabetes mellitus (n = 10). The pharmacodynamics profile of a single dose of short-acting insulin (insulin lispro) was investigated, using a controlled environmental chamber, under three environmental conditions: (a) temperature: 15°C and humidity: 10%; (b) temperature: 30°C and humidity: 10%; and (c) temperature: 30°C and humidity: 60%. A euglycaemic glucose clamp technique ensured constant blood glucose of 100 mg/dL (5.5 mmol/L). The following pharmacodynamic endpoints were calculated: maximum glucose infusion rate (GIRmax ), time to GIRmax (tGIRmax ), total area under the curve (AUC) for GIR from 0-6 hours (AUCGIR.0-6h ), and partial AUCs (AUCGIR.0-1h , AUCGIR.0-2h and AUCGIR.2-6h ). RESULTS: Higher temperature (30°C) under 10% fixed humidity conditions resulted in greater GIRmax (P = 0.04) and a later tGIR.max (P = 0.049) compared to lower temperature (15°C). Humidity did not affect any pharmacodynamic parameter. When the combined effects of temperature and humidity were explored, tGIR.max (P = 0.008) occurred earlier, with a lower late insulin pharmacodynamic effect (AUCGIR.2-6h ; P = 0.017) at a temperature of 15°C and humidity of 10% compared to a temperature of 30°C and humidity of 60%. CONCLUSIONS: High ambient temperature resulted in a greater insulin peak effect compared to low ambient temperature, with the contribution of high relative humidity apparent only at high ambient temperature. This suggests that patients with type 1 diabetes mellitus who are entering higher environmental temperatures, with or without high humidity, could experience more hypoglycaemic events.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Ambiente , Humedad , Insulina/farmacocinética , Temperatura , Adolescente , Adulto , Área Bajo la Curva , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/sangre , Hipoglucemiantes/farmacocinética , Insulina/administración & dosificación , Insulina/sangre , Insulina Lispro/administración & dosificación , Insulina Lispro/sangre , Insulina Lispro/farmacocinética , Insulina de Acción Prolongada/administración & dosificación , Insulina de Acción Prolongada/sangre , Insulina de Acción Prolongada/farmacocinética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
AIM: The primary objective of this study was to compare blood glucose (BG) excursions between East Asian and Caucasian patients with type 2 diabetes mellitus (T2DM) who were injection-naive, had inadequate glycemic control with oral antihyperglycemic medications, and who required initiation with injectable therapy. METHODS: This retrospective pooled analysis included individual patient data from completed clinical trials (Insulin lispro injection/dulaglutide development programs, first patient visit ≥1997). All included patients were ≥18 years, were East Asian or Caucasian, and had data for self-monitored BG at baseline. The primary outcome, BG excursion at baseline (least-squares mean, standard error), was compared between patient groups using an analysis of covariance with race as the fixed effect. Independent covariates included baseline body weight, baseline HbA1c, age, and duration of T2DM. RESULTS: Caucasian (n = 6779) and East Asian (n = 1638) patients from 21 trials were included. BG excursions were significantly higher for East Asian than Caucasian patients at breakfast (4.03 [0.075] vs 2.59 [0.045] mmol/L), lunch (3.37 [0.080] vs 1.43 [0.049] mmol/L), and dinner (3.16 [0.080] vs 1.74 [0.047] mmol/L) (P < 0.001 adjusted analyses). Similar findings were observed for the unadjusted analyses. At each time point, postprandial BG was significantly higher for East Asian than Caucasian patients (with adjusted and unadjusted analyses). CONCLUSION: These findings suggest that BG excursion and postprandial BG are higher among East Asian patients with T2DM than Caucasian patients. In addition, these findings may help clinicians select appropriate treatments for East Asian patients with T2DM who require injection therapy.