Insulin glulisine (glulisine), a human insulin analogue with a rapid-acting time-action profile, has been developed to fulfil the mealtime (bolus) insulin requirement in patients with diabetes. The aim of this multinational, multi-centre, controlled, open-label, randomized, parallel-group study was to compare the efficacy and safety of insulin glulisine (glulisine) to that of insulin lispro (lispro) in adults diagnosed with Type 1 diabetes. Of the 683 patients randomized, 672 received treatment (339 patients received glulisine, 333 patients received lispro). Over the 26-week study, a similar reduction in mean HbA1c occurred in both groups (adjusted mean change from baseline -0.14% in both groups). The basal insulin dose was relatively unchanged from baseline in the glulisine group but increased in the lispro group (glulisine: 0.12 IU vs. lispro: 1.82 IU; p = 0.0001). As a consequence, total daily insulin dose decreased in the glulisine group but increased in the lispro group (glulisine: -0.86 IU vs. lispro: 1.01 IU; p = 0.0123). There was no relevant difference between the two groups in the reporting of symptomatic hypoglycaemia (overall, nocturnal and severe). This study demonstrates that glulisine provides equivalent glycaemic control to lispro. The clinical relevance of any difference in total daily insulin dose remains to be established.
Aims: The primary objective was to demonstrate that basal insulin peglispro (BIL) was noninferior compared with insulin glargine (GL) for haemoglobin A1c (HbA1c) at 26 weeks with a non-inferiority margin of 0.4%. Results: At 26 weeks, mean HbA1c was 7.06% AE 0.04% and 7.43% AE 0.06% for patients assigned to BIL (N = 295) and GL (N = 160), respectively (difference -0.37% [95% CI: −0.50 to −0.23], P < .001); more patients on BIL achieved HbA1c <7% (44.9% vs 27.5%, P < .001). Compared with GL, patients using BIL lost weight, with lower fasting serum glucose and betweenday fasting blood glucose variability, and 36% less nocturnal hypoglycemia, 29% more total hypoglycemia and more severe hypoglycemia. Total and prandial insulin doses were lower with BIL; basal insulin doses were higher. Alanine aminotransferase increased with BIL, with more patients having elevations ≥3 × ULN. BIL treatment was associated with more frequent injection site reactions and an increase from baseline in serum triglycerides. Conclusions:In patients with type 1 diabetes, treatment with BIL compared to GL for 26 weeks was associated with lower HbA1c, less nocturnal hypoglycemia, lower glucose variability and weight loss. Increases in total and severe hypoglycemia, triglycerides, aminotransferases and injection site reactions were also noted. K E Y W O R D Sbasal insulin, glycaemic control, hypoglycaemia, randomised trial, type 1 diabetes
OBJECTIVE -To compare the efficacy and safety profile of adding inhaled human insulin (INH) (Exubera) or glibenclamide to metformin monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS -We conducted an open-label, parallel, 24-week multicenter trial. Patients uncontrolled on metformin were randomized to adjunctive INH (n ϭ 243) or glibenclamide (n ϭ 233). Before randomization, patients were divided into two HbA 1c (A1C) arms: Ն8 to Յ9.5% (moderately high) and Ͼ9.5 to Յ12% (very high). The primary efficacy end point was A1C change from baseline.RESULTS -Mean adjusted A1C changes from baseline were Ϫ2.03 and Ϫ1.88% in the INH and glibenclamide groups, respectively; between-treatment difference Ϫ0.17% (95% CI Ϫ0.34 to 0.01; P ϭ 0.058), consistent with the noninferiority criterion. In the A1C Ͼ9.5% arm, inhaled insulin demonstrated a significantly greater reduction in A1C than glibenclamide, between-treatment difference Ϫ0.37% (Ϫ0.62 to Ϫ0.12; P ϭ 0.004). In the A1C Յ9.5% arm, between-treatment difference was 0.04% (Ϫ0.19 to 0.27; P ϭ 0.733). Hypoglycemia (events per subject-month) was greater with INH (0.18) than glibenclamide (0.08), risk ratio 2.24 (1.58 -3.16), but there were no associated discontinuations. Other adverse events, except increased cough in the INH group, were similar. At week 24, changes from baseline in pulmonary function parameters were small. Insulin antibody binding increased more with INH but did not have any associated clinical manifestations.CONCLUSIONS -In patients with type 2 diabetes poorly controlled on metformin, adding INH or glibenclamide was similarly effective in improving glycemic control, and both were well tolerated. A predefined subgroup with very high A1C (Ͼ9.5%) was more effectively treated with the addition of INH. Diabetes Care 29:1818 -1825, 2006T he goal of therapy in type 2 diabetes management is to reach and sustain near-normal glycemic levels (HbA 1c [A1C] of Յ7%) (1,2). Since the American Diabetes Association (ADA) dropped the 8% "action threshold" in 2004 in favor of a general recommendation to treat most patients to A1C Ͻ7% (3), levels above this goal have signaled the need to intensify therapy. Oral antidiabetic agent monotherapy is associated with a high secondary failure rate (4,5). The usual next step is progression to oral agent combination therapy; the most extensively studied and widely used combination being a sulfonylurea plus metformin (6). Despite poor glycemic control on average in the general population of patients with type 2 diabetes (7), there is often a reluctance to initiate insulin therapy because of concerns from both physicians (8,9) and patients (10,11).Improvements in insulin formulation may overcome some of these concerns (12). Inhaled human insulin (INH; Exubera [insulin human {rDNA origin} Inhalation Powder]), which has recently been approved in both the U.S. and European Union for the treatment of type 1 and type 2 diabetes in adults, has proven effective in patients failing to obtain adequate glyce...
OBJECTIVE -To compare the efficacy and safety profile of adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS -We performed an open-label, parallel, 24-week, multicenter trial. At week Ϫ1, patients uncontrolled on sulfonylurea monotherapy were divided into two HbA 1c (A1C) arms: Ն8 to Յ9.5% (moderately high) and Ͼ9.5 to Յ12% (very high). Patients were randomized to adjunctive premeal INH (n ϭ 225) or metformin (n ϭ 202). The primary efficacy end point was change in A1C from baseline.RESULTS -In the A1C Ͼ9.5% arm, INH demonstrated a significantly greater reduction in A1C than metformin. Mean adjusted changes from baseline were Ϫ2.17 and Ϫ1.79%, respectively; between-treatment difference was Ϫ0.38% (95% CI Ϫ0.63 to Ϫ0.14, P ϭ 0.002). In the A1C Յ9.5% arm, mean adjusted A1C changes were Ϫ1.94 and Ϫ1.87%, respectively (Ϫ0.07% [Ϫ0.33 to 0.19], P ϭ 0.610), consistent with the noninferiority criterion. Hypoglycemia (events/ subject-month) was greater in the INH (0.33) than in the metformin (0.15) group (risk ratio 2.16 [95% CI 1.67-2.78]), but there were no associated discontinuations. Other adverse events, except increased cough in the INH group, were similar. At week 24, changes in pulmonary function parameters were small and comparable between groups. Insulin antibody binding increased more with INH but did not have any associated clinical manifestations.CONCLUSIONS -In patients with type 2 diabetes poorly controlled on a sulfonylurea (A1C Ͼ9.5%), the addition of premeal INH significantly improves glycemic control compared with adjunctive metformin and is well tolerated.
Genes of the major histocompatibility complex (MHC) have been shown to influence social signalling and mate preferences in many species, including humans. First observations suggest that MHC signalling may also affect female fertility. To test this hypothesis, we exposed 191 female horses () to either an MHC-similar or an MHC-dissimilar stimulus male around the time of ovulation and conception. A within-subject experimental design controlled for non-MHC-linked male characteristics, and instrumental insemination with semen of other males ( = 106) controlled for potential confounding effects of semen or embryo characteristics. We found that females were more likely to become pregnant if exposed to an MHC-dissimilar than to an MHC-similar male, while overall genetic distance to the stimulus males (based on microsatellite markers on 20 chromosomes) had no effect. Our results demonstrate that early pregnancy failures can be due to maternal life-history decisions (cryptic female choice) influenced by MHC-linked social signalling.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.