Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

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These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.

Objective:This study investigated the efficacy and safety of insulin degludec (IDeg) once daily (OD), varying injection timing day to day in subjects with type 1 diabetes.Research Design and Methods:This 26-week, open-label, treat-to-target, noninferiority trial compared IDeg forced flexible (Forced-Flex) OD (given in a fixed schedule with a minimum 8 and maximum 40 hours between doses) with IDeg or insulin glargine (IGlar) given at the same time daily OD. In the 26-week extension, all IDeg subjects were transferred to a free-flexible (Free-Flex) regimen, which allowed any-time-of-day dosing, and compared with subjects continued on IGlar.Results:After 26 treatment weeks, mean glycosylated hemoglobin was reduced with IDeg Forced- Flex (−0.40%), IDeg (−0.41%), and IGlar (−0.58%). IDeg Forced-Flex noninferiority was achieved. Fasting plasma glucose reductions were similar with IDeg Forced-Flex and IGlar but greater with IDeg (−2.54 mmol/L) than IDeg Forced-Flex (−1.28 mmol/L) (P = .021). At week 52, IDeg Free-Flex subjects had similar glycosylated hemoglobin but greater fasting plasma glucose reductions than IGlar subjects (−1.07 mmol/L) (P = .005). Confirmed hypoglycemia rates (plasma glucose <3.1 mmol/L or severe hypoglycemia) were similar at weeks 26 and 52. Nocturnal confirmed hypoglycemia was lower with IDeg Forced-Flex vs IDeg (37%; P = .003) and IGlar (40%; P = .001) at week 26 and 25% lower with IDeg Free-Flex vs IGlar (P = .026) at week 52.Conclusions:IDeg can be administered OD at any time of day, with injection timing varied without compromising glycemic control or safety vs same-time-daily IDeg or IGlar. This may improve basal insulin adherence by allowing injection-time adjustment according to individual needs.

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Six-month preoperative octreotide treatment might improve surgical cure rate in newly diagnosed acromegalic patients with macroadenomas. These results have to be confirmed in future studies.

The results suggest that use of TM technology can be a relevant alternative and supplement to usual care, at least for patients with more superficial ulcers.

AimsTo evaluate the efficacy and safety of two insulin intensification strategies for patients with type 2 diabetes previously treated with basal insulin – insulin degludec (IDeg) and insulin aspart (IAsp) – administered as a co‐formulation (IDegAsp) or as a basal‐bolus regimen (IDeg and IAsp in separate injections).MethodsThis 26‐week, open‐label, treat‐to‐target, phase IIIb, non‐inferiority trial randomized patients (1 : 1) to IDegAsp twice daily with main meals (n = 138; IDegAsp group) or IDeg once daily and IAsp 2–4 times daily (n = 136; IDeg+IAsp group).ResultsAfter 26 weeks, the mean glycated haemoglobin (HbA1c) level was 7.0% (53 mmol/mol) for the IDegAsp group and 6.8% (51 mmol/mol) for the IDeg+IAsp group (Δ%HbA1c from baseline −1.31 and −1.50%, respectively). The non‐inferiority of IDegAsp versus IDeg+IAsp was not confirmed for mean change in HbA1c [estimated treatment difference (ETD) 0.18, 95% confidence interval (CI) −0.04, 0.41; p = non‐significant]. No significant differences were observed in the proportion of patients achieving HbA1c <7.0% (56.5 and 59.6%, respectively). IDegAsp treatment resulted in a significantly lower total daily insulin dose, a smaller change in body weight, numerically lower rates of confirmed hypoglycaemia (self‐reported plasma glucose <3.1 mmol/l; rate ratio 0.81; p = non‐significant), and nocturnal confirmed hypoglycaemic episodes (rate ratio 0.80; p = non‐significant) versus IDeg+IAsp. Patient‐reported outcome scores for social functioning were significantly higher for IDegAsp versus IDeg+IAsp (ETD 2.2; 95% CI 0.3, 4.1; p < 0.05).ConclusionsBoth intensification strategies effectively improved glycaemic control. Although non‐inferiority was not confirmed, there were no significant differences between the groups that could affect clinical utility.