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.

Diabetes mellitus is a chronic disease characterized by high social, economic and health burden, mostly due to the high incidence and morbidity of diabetes complications. Numerous studies have shown that optimizing metabolic control may reduce the risk of micro and macrovascular complications related to the disease, and the algorithms suggest that an appropriate and timely step of care intensification should be proposed after 3 months from the failure to achieve metabolic goals. Nonetheless, many population studies show that glycemic control in diabetic patients is often inadequate. The phenomenon of clinical inertia in diabetology, defined as the failure to start a therapy or its intensification/de-intensification when appropriate, has been studied for almost 20 years, and it is not limited to diabetes care, but also affects other specialties. In the present manuscript, we have documented the issue of inertia in its complexity, assessing its dimensions, its epidemiological weight, and its burden over the effectiveness of care. Our main goal is the identification of the causes of clinical inertia in diabetology, and the quantification of its social and health-related consequences through the adoption of appropriate indicators, in an effort to advance possible solutions and proposals to fight and possibly overcome clinical inertia, thus improving health outcomes and quality of care.

IntroductionThe aim of the study was to evaluate whether the reduction in glycated hemoglobin (HbA1c) observed in clinical trials with liraglutide in type 2 diabetes (T2D) could be attained in routine clinical practice.MethodsReaL was a multicenter, non-interventional, observational, retrospective, longitudinal study on the effectiveness of liraglutide, a human glucagon-like peptide-1 analog, in individuals with T2D treated in daily practice in Italy. Between 26 March and 16 November 2015, data were taken from clinical records of patients aged ≥ 18 years with treatment follow-up data of up to 24 months and who received their first prescription of liraglutide in 2011.ResultsA total of 1723 patients were included in the analysis. At baseline, mean age was 58.9 years, duration of diabetes was 9.6 years, and HbA1c was 8.3%. At 12 months, 36.1% of patients were prescribed the maximum 1.8 mg dose; 43.5% [95% confidence interval (CI): 40.9; 46.2] of patients attained the primary outcome of a reduction in HbA1c of ≥ 1% point at 12 months. At 24 months, 40.9% (95% CI 38.1; 43.7) of patients had attained the HbA1c target of ≤ 7%. Additionally, body weight significantly decreased by 3.4 kg (95% CI − 3.6; − 3.1, p < 0.0001).ConclusionIn this observational study conducted in routine clinical practice for up to 2 years, treatment with liraglutide improved HbA1c and reduced body weight in a similar fashion to that observed under randomized clinical trial conditions. The data support the use of liraglutide as an effective treatment for T2D in clinical practice.FundingNovo Nordisk S.p.A.Trial RegistrationClinicalTrials.gov identifier, NCT02255266.Electronic supplementary materialThe online version of this article (10.1007/s12325-017-0652-2) contains supplementary material, which is available to authorized users.

As GH therapy has been reported to increase growth velocity in children with Down's syndrome (DS), we studied the GH-IGF-I axis in some DS patients affected by growth retardation without serious congenital malformation, malnutrition or pathological thyroid or adrenal function. IGF-I and IGF-II were evaluated in 39 patients in basal conditions. The patients were subsequently divided into two groups with respect to the IGF-I basal value: Group 1 (GR 1) consisting of patients with abnormally low basal IGF-I concentration as compared to age matched control subjects, group 2 (GR 2) consisting of patients with IGF-I in the normal range. In 6 GR 1 patients and 12 GR 2 patients we evaluated GH and IGF-I concentrations after stimulation with arginine (0.5 g/kg bw), and recombinant GH (4 IU im). In the same patients, GH radioreceptor assay and serum GH-binding protein were evaluated. In all patients IGF-II proved normal (534 +/- 23 ng/ml; mean +/- SE), while IGF-I was pathological in 36% of subjects. The cause of the defective IGF-I secretion in these patients does not seem to depend on an impaired GH axis, as no significant difference in arginine-stimulated GH peak values was seen between GR 1 (29.6 +/- 5.3 ng/ml) and GR 2 (15.1 +/- 2.24 ng/ml). IGF-I concentration evaluated 12, 24, and 48 h after arginine stimulation was significantly increased only in GR 2 patients (peak value: 0.95 +/- 0.1, p = 0.0003 vs baseline; GR 1: 0.34 +/- 0.05 U/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

AimsThere is an unmet need among healthcare providers to identify subgroups of patients with type 2 diabetes who are most likely to respond to treatment.MethodsData were taken from electronic medical records of participants of an observational, retrospective study in Italy. We used logistic regression models to assess the odds of achieving glycated haemoglobin (HbA1c) reduction ≥ 1.0% point after 12-month treatment with liraglutide (primary endpoint), according to various patient-related factors. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify distinct homogeneous patient subgroups with different odds of achieving the primary endpoint. ResultsData from 1325 patients were included, of which 577 (43.5%) achieved HbA1c reduction ≥ 1.0% point (10.9 mmol/mol) after 12 months. Logistic regression showed that for each additional 1% HbA1c at baseline, the odds of reaching this endpoint were increased 3.5 times (95% CI: 2.90–4.32). By use of RECPAM analysis, five distinct responder subgroups were identified, with baseline HbA1c and diabetes duration as the two splitting variables. Patients in the most poorly controlled subgroup (RECPAM Class 1, mean baseline HbA1c > 9.1% [76 mmol/mol]) had a 28-fold higher odds of reaching the endpoint versus patients in the best-controlled group (mean baseline HbA1c ≤ 7.5% [58 mmol/mol]). Mean HbA1c reduction from baseline was as large as − 2.2% (24 mol/mol) in the former versus − 0.1% (1.1 mmol/mol) in the latter. Mean weight reduction ranged from 2.5 to 4.3 kg across RECPAM subgroups. ConclusionsGlycaemic response to liraglutide is largely driven by baseline HbA1c levels and, to a lesser extent, by diabetes duration.