Background: It is thought that a reduction in the frequency of basal insulin injections might facilitate treatment acceptance and adherence among patients with type 2 diabetes. Insulin icodec is a basal insulin analogue designed for once-weekly administration that is in development for the treatment of diabetes. Methods: We conducted a 26-week, randomized, double-blind, double-dummy, phase 2 trial to investigate the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100 in patients who had not previously received long-term insulin treatment and whose type 2 diabetes was inadequately controlled (glycated hemoglobin level, 7.0 to 9.5%) while taking metformin with or without a dipeptidyl peptidase 4 inhibitor. The primary end point was the change in glycated hemoglobin level from baseline to week 26. Safety end points, including episodes of hypoglycemia and insulin-related adverse events, were also evaluated. Results: A total of 247 participants were randomly assigned (1:1) to receive icodec or glargine. Baseline characteristics were similar in the two groups; the mean baseline glycated hemoglobin level was 8.09% in the icodec group and 7.96% in the glargine group. The estimated mean change from baseline in the glycated hemoglobin level was -1.33 percentage points in the icodec group and -1.15 percentage points in the glargine group, to estimated means of 6.69% and 6.87%, respectively, at week 26; the estimated between-group difference in the change from baseline was -0.18 percentage points (95% CI, -0.38 to 0.02, P = 0.08). The observed rates of hypoglycemia with severity of level 2 (blood glucose level, (54 mg per deciliter) or level 3 (severe cognitive impairment) were low (icodec group, 0.53 events per patient-year; glargine group, 0.46 events per patient-year; estimated rate ratio, 1.09; 95% CI, 0.45 to 2.65). There was no between-group difference in insulin-related key adverse events, and rates of hypersensitivity and injection-site reactions were low. Most adverse events were mild, and no serious events were deemed to be related to the trial medications. Conclusions: Once-weekly treatment with insulin icodec had glucose-lowering efficacy and a safety profile similar to those of once-daily insulin glargine U100 in patients with type 2 diabetes. (Funded by Novo Nordisk; NN1436-4383 ClinicalTrials.gov number, NCT03751657.).
COBISS.SI-ID: 29374467
Background Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) have become firmly established in the treatment of type 2 diabetes and obesity, disorders frequently associated with diminished reproductive health. Understanding of the role of GLP-1 and GLP-1 RAs in reproduction is currently limited and largely unaddressed in clinical studies. Objective and rationale The purpose of this narrative review is to provide a comprehensive overview of the role of GLP-1 in reproduction and to address a therapeutic perspective that can be derived from these findings. Search methods We performed a series of PubMed database systemic searches, last updated on 1 February 2019, supplemented by the authors- knowledge and research experience in the field. A search algorithm was developed incorporating the terms glucagon-like peptide-1, GLP-1, glucagon-like peptide-1 receptor, GLP-1R, or incretins, and this was combined with terms related to reproductive health. The PICO (Population, Intervention, Comparison, Outcome) framework was used to identify interventional studies including GLP-1 RAs and dipeptidyl peptidase-4 (DPP-4) inhibitors, which prevent the degradation of endogenously released GLP-1. We identified 983 potentially relevant references. At the end of the screening process, we included 6 observational (3 preclinical and 3 human) studies, 24 interventional (9 preclinical and 15 human) studies, 4 case reports, and 1 systematic and 2 narrative reviews. Outcomes The anatomical...
COBISS.SI-ID: 34390233
OBJECTIVE It is well established that diabetic nephropathy increases the risk of cardiovascular disease (CVD), but how severe diabetic retinopathy (SDR) impacts this risk has yet to be determined. RESEARCH DESIGN AND METHODS The cumulative incidence of various CVD events, including coronary heart disease (CHD), peripheral artery disease (PAD), and stroke, retrieved from registries, was evaluated in 1,683 individuals with at least a 30-year duration of type 1 diabetes drawn from the Finnish Diabetic Nephropathy Study (FinnDiane). The individuals were divided into four groups according to the presence of diabetic kidney disease (DKD) and/or SDR (+DKD/+SDR, +DKD/-SDR, -DKD/+SDR, and -DKD/-SDR) at baseline visit. Furthermore, age-specific incidences were compared with 4,016 control subjects without diabetes. SDR was defined as laser photocoagulation and DKD as estimated glomerular filtration rate (60 mL/min/1.73 m2. RESULTS During 12,872 person-years of follow-up, 416 incident CVD events occurred. Even in the absence of DKD, SDR increased the risk of any CVD (hazard ratio 1.46 [95% CI 1.11–1.92]; P ( 0.01), after adjustment for diabetes duration, age at diabetes onset, sex, smoking, blood pressure, waist-to-hip ratio, history of hypoglycemia, and serum lipids. In particular, SDR alone was associated with the risk of PAD (1.90 [1.13–3.17]; P ( 0.05) and CHD (1.50 [1.09–2.07; P ( 0.05) but not with any stroke. Moreover, DKD increased the CVD risk further (2.85 [2.13–3.81]; P ( 0.001). However, the risk was above that of the control subjects without diabetes also in patients without microvascular complications, until the patients reached their seventies. CONCLUSIONS SDR alone, even without DKD, increases cardiovascular risk, particularly for PAD, independently of common cardiovascular risk factors in long-standing type 1 diabetes. More remains to be done to fully understand the link between SDR and CVD. This knowledge could help combat the enhanced cardiovascular risk beyond currently available regimens.
COBISS.SI-ID: 5365932
Aims: This post hoc analysis of the DUAL II and DUAL IX trials, investigated the efficacy and safety of initiating insulin degludec/liraglutide (IDegLira) in patients with type 2 diabetes (T2D) that had discontinued pre-trial sulphonylurea (SU) or dipeptidyl peptidase-4 inhibitors (DPP4is) vs patients not previously treated with these regimens. This analysis provides guidance to clinicians considering IDegLira treatment for patients currently using SUs or DPP4is. Materials and methods:In DUAL II, patients with T2D uncontrolled on basal insulin and metformin +- SU/glinides were randomized to insulin degludec or IDegLira (both capped at 50 U). In DUAL IX, patients were randomized to insulin glargine U100 (no maximum dose) or IDegLira, as add-on to sodium-glucose co-transporter-2 inhibitors +- oral antidiabetic drugs. In this post hoc analysis, patients were grouped according to pre-trial use of SU (DUAL II) or DPP4i (DUAL IX). Results: Regardless of pre-trial SU/DPP4i use, IDegLira was favourable vs insulin comparators with respect to change in HbA1c and body weight. Lower hypoglycaemia ratesand comparable end-of-trial daily insulin dose were achieved with IDegLira, regardless of pre-trial regimen. There was no clinically relevant increase in mean self-measured blood glucose in the early weeks after IDegLira initiation. There was no statistically significant interaction between the randomized treatments and previous SU/DPP4i use. Conclusions: IDegLira was more favourable...
COBISS.SI-ID: 34629337