In patients with uncontrolled type 2 diabetes on IGlar U100 and metformin, IDegLira treatment elicited HbA reductions comparable to basal-bolus, with statistically superior lower hypoglycemia rates and weight loss versus weight gain.
AimsTo compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin‐naïve patients with type 2 diabetes.Research design and methodsThis 32‐week, open‐label, non‐inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre‐breakfast plasma glucose (PG) readings (n = 210), or twice weekly, based on the mean of 3 pre‐breakfast PG readings (n = 210).ResultsMean HbA1c decreased from 8.2% (65 mmol/mol) to 6.1% (43 mmol/mol) with once‐weekly titration and from 8.1% (65 mmol/mol) to 6.0% (42 mmol/mol) with twice‐weekly titration; non‐inferiority was confirmed (estimated treatment difference: 0.12% [−0.04; 0.28]95%
CI, 1.30 mmol/mol [−0.41; 3.01]95%
CI). Approximately 90% of patients achieved HbA1c < 7% in each arm. Mean fasting PG was similar after 32 weeks. Weight change was −1.0 kg vs −2.0 kg for once‐weekly vs twice‐weekly titration. Rates of severe or blood glucose‐confirmed symptomatic hypoglycaemia were low in both arms: 0.16 events/patient‐year of exposure (PYE) for once‐weekly, 0.76 events/PYE for twice‐weekly titration. Mean IDegLira dose at 32 weeks was 41 dose steps (41 U IDeg/1.48 mg Lira) for both arms. Overall adverse event rates were 207.8 and 241.3 events/100 PYE with once‐weekly and twice‐weekly titration, respectively.ConclusionA pragmatic titration algorithm with once‐weekly adjustments based on 2 PG readings resulted in a safety and glycaemic efficacy profile similar to that with twice‐weekly adjustments based on 3 preceding PG values in insulin‐naïve patients.
Aim
To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine 100 units/mL (IGlar U100) as add‐on to sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor therapy.
Materials and methods
In this 26‐week, phase IIIb, open‐label, parallel‐group, treat‐to‐target trial, conducted at 74 sites in 11 countries, insulin‐naïve people aged ≥18 years with glycated haemoglobin (HbA1c) 53–97 mmol/mol (7.0–11.0%), body mass index 20–40 kg/m2 and inadequately controlled type 2 diabetes (T2D) on SGLT2 inhibitor ± oral antidiabetic drugs were randomized 1:1 to once‐daily IDegLira or IGlar U100, both as add‐on to existing therapy. The primary endpoint was change in HbA1c from baseline to week 26.
Results
A total of 210 participants were randomized to each treatment arm. Mean HbA1c reductions were 21 mmol/mol (1.9%‐points) with IDegLira and 18 mmol/mol (1.7%‐points) with IGlar U100; confirming non‐inferiority (P < 0.0001) and superiority of IDegLira (difference in HbA1c change –3.90 mmol/mol; 95% confidence interval [CI] –5.45; –2.35 (−0.36%‐points; 95% CI –0.50, –0.21)). Superiority for IDegLira over IGlar U100 was also confirmed for: body weight (difference −1.92 kg; 95% CI –2.64, –1.19); severe or blood‐glucose‐confirmed symptomatic hypoglycaemia (rate ratio 0.42; 95% CI 0.23, 0.75); total daily insulin dose (difference −15.37 U; 95% CI –19.60, −11.13). The overall treatment‐emergent adverse event rate was higher with IDegLira as a result of higher increased lipase and nausea rates.
Conclusions
The favourable safety and efficacy profile of IDegLira in people with uncontrolled T2D on SGLT2 inhibitors, and lower weight gain and hypoglycaemia risk versus IGlar U100, suggest that clinicians should consider IDegLira initiation in this population.
BackgroundAnxiety in relation to surgery is a well-known problem. Melatonin offers an atoxic alternative to benzodiazepines in ameliorating this condition in the pre-and postoperative period.
ObjectivesTo assess the effect of melatonin on pre-and postoperative anxiety in adults when comparing melatonin with placebo or when comparing melatonin with benzodiazepines.
Search methodsThe following databases were searched on 19 April 2013: CENTRAL, MEDLINE, EMBASE, CINAHL and Web of Science. For ongoing trials and protocols we searched clinicaltrials.gov, Current Controlled Trials and the World Health Organization (WHO) International Clinical Trials Registry Platform. We reran the search in October 2014. We will deal with any studies of interest when we update the review.
Selection criteriaRandomized, placebo-controlled or standard treatment-controlled, or both, studies that evaluated the effect of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both genders (15 to 90 years of age) undergoing any kind of surgical procedure in which it was necessary to use general, regional or topical anaesthesia.
Data collection and analysisData were extracted independently by two review authors. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimen, preoperative anxiety outcome measures and postoperative anxiety outcome measures.
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