RESUMEN
OBJECTIVE: We compared two strategies initiating and intensifying insulin treatment and tested for noninferiority of premixed insulin to basal ± mealtime insulin analog in patients eating light breakfasts. RESEARCH DESIGN AND METHODS: This randomized, open-label, 48-week study compared two algorithms. Up to three injections of insulin lispro mix 25 and/or insulin lispro mix 50 (premix; premixed insulin lispro) or basal insulin glargine plus up to three injections of insulin lispro (basal+; glargine + insulin lispro) were used in type 2 diabetic patients uncontrolled with oral antihyperglycemic medication and consuming <15% daily calories at breakfast. The hypothesis was to test noninferiority of premix to basal+ for glycemic control measured by HbA1c after 48 weeks, assessed using ANCOVA with a 0.4% margin. RESULTS: Patients (n = 344; 176 [51%] females; mean [SD] age 54.3 [8.8] years; BMI 29.4 [4.6] kg/m(2); baseline HbA1c 9.02 [0.97]%) were randomized to premix (n = 171) or basal+ (n = 173). In the per-protocol analysis (n = 230), least squares means (95% CI) end point HbA1c were 7.40% (7.15-7.65) and 7.55% (7.27-7.82) in respective arms. Between-treatment difference was -0.14% (-0.42 to 0.13), with noninferiority met. Significantly more patients in premix achieved HbA1c targets of <7.0% compared with basal+ (48.2 vs. 36.2%; P = 0.024). Self-monitored blood glucose profiles, body weight changes, total insulin doses, and overall hypoglycemia (65 vs. 60%) were similar in premix and basal+ (P = 0.494), except nocturnal episodes (34.3 vs. 23.7%; P = 0.018) were more common in premix. CONCLUSIONS: Both intensive insulin strategies improved glycemic control; however, final HbA1c levels were seen above those achieved in previous treat-to-target trials, likely due to the inadequate insulin titrations and probably due to the complexity of tested insulin regimens. A higher percentage of patients achieved target HbA1c <7% with multiple premixed insulins, but this treatment resulted in more nocturnal hypoglycemia than a basal-bolus regimen.
Asunto(s)
Desayuno , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina Lispro/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Adulto , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Inyecciones , Insulina Glargina , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Studies of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) are needed to determine the durability of metabolic response and tolerability associated with long-term treatment. OBJECTIVE: The present study was conducted to provide long-term data on glycemic control, weight changes, and tolerability of exenatide 10 µg BID treatment in patients with type 2 diabetes mellitus who have failed to achieve glycemic targets with oral antihyperglycemic medication. METHODS: In this uncontrolled, open-label trial with treatment up to 156 weeks, patients received exenatide 10 µg BID while continuing treatment with metformin and/or a sulfonylurea (SFU). Intent-to-treat (ITT), 52-, 100-, and 132-week completer populations were defined. Metabolic changes were analyzed in the completer and ITT populations; adverse events (AEs) were summarized in the ITT population. Descriptive statistics were used for absolute and change-from-baseline data. Within-treatment comparisons were conducted using the paired t test. RESULTS: Of 155 patients in the ITT population (mean [SD]: age, 59 [9] years; 56% female; duration of diabetes, 9.1 [5.9] years; weight, 88.8 [16.5] kg; body mass index, 31.9 [4.7] kg/m(2); hemoglobin [Hb] A(1c), 8.7% [1.2%]), 133, 111, and 103 patients completed 52, 100, and 132 weeks of treatment, respectively. In the ITT population, the mean (SE) change in HbA(1c) from baseline to week 132 was -1.0% (0.10%) (P < 0.0001). In patients completing 52, 100, and 132 weeks, HbA(1c) changes from baseline to end point were -1.3% (0.10%), -1.0% (0.12%), and -1.0 (0.13%) (P < 0.0001), with 40% of patients achieving HbA(1c) <7% at 132 weeks. Patients in the ITT and completer populations experienced mean (SE) weight changes of -3.7 (0.39) kg and -3.9 (0.51) kg (P < 0.0001) at week 132. Improved glycemic control and weight loss occurred in 63% of patients in the completer population at week 132. In addition, 38% of completers at week 132 achieved HbA(1c) <7% without weight gain. No relationship was found between the development of antiexenatide antibodies and change in HbA(1c). The most common AEs were gastrointestinal in nature, reported in 46% of patients and leading to discontinuation in 7 cases. Serious AEs were reported in 26% of patients, and 18% withdrew due to a treatment-emergent AE. Of 24% of patients in whom hypoglycemia was reported, 22% were on SFU or metformin + SFU combination, and 2% were on metformin. CONCLUSIONS: The findings from this open-label, single-arm study characterized the response to exenatide 10 µg BID for up to 132 weeks. Significant, persistent improvements in HbA(1c) and weight were observed in patients receiving exenatide BID, with reported AEs consistent with those from studies of shorter duration. ClinicalTrials.gov identifier: NCT00044668.