Managing weight and glycaemic targets in people with type 2 diabetes—How far have we come?

Introduction: As the vast majority of people with type 2 diabetes (T2D) are also overweight or obese, healthcare professionals (HCP) are faced with the task of addressing both weight management and glucose control. In this narrative review, we aim to identify the challenges of reaching and maintaining body weight targets in people with T2D and highlight current and future treatment interventions. Methods: A search of the PubMed database was conducted using the search terms “diabetes” and “weight loss.”. Results: According to emerging evidence, treating obesity may be antecedent to the development and progression of T2D. While clinical benefits typically set in upon achieving a weight loss of 3–5%, these benefits are progressive leading to further health improvements, and weight loss of >15% can have a disease-modifying effect in people with T2D, an outcome that up to recently could not be achieved with any blood glucose-lowering pharmacotherapy. However, advanced treatment options with weight-loss effects currently in development including the dual GIP/GLP-1 receptor agonists may enable simultaneous achievement of individual glycemic and weight goals. Conclusion: Despite considerable therapeutic progress, there is still a large unmet medical need in patients with T2D who miss their individualized glycemic and weight-loss targets. Nonetheless, it is to be expected that development of future therapies and their use will favourably change the scenario of weight and glucose control in T2D

Benefits of combination of insulin degludec and liraglutide are independent of baseline glycated haemoglobin level and duration of type 2 diabetes

AIM: To evaluate, using post hoc analyses, whether the novel combination of a basal insulin, insulin degludec, and a glucagon‐like peptide‐1 receptor agonist, liraglutide (IDegLira), was consistently effective in patients with type 2 diabetes (T2D), regardless of the stage of T2D progression. METHODS: Using data from the DUAL I extension [insulin‐naïve patients uncontrolled on oral antidiabetic drugs (OADs), n = 1660, 52 weeks] and DUAL II (patients uncontrolled on basal insulin plus OADs, n = 398, 26 weeks) randomized trials, the efficacy of IDegLira was investigated with regard to measures of disease progression stage including baseline glycated haemoglobin (HbA1c), disease duration and previous insulin dose. RESULTS: Across four categories of baseline HbA1c (≤7.5–9.0%), HbA1c reductions were significantly greater with IDegLira (1.1–2.5%) compared with IDeg or liraglutide alone in DUAL I. In DUAL II, HbA1c reductions were significantly greater with IDegLira (0.9–2.5%) than with IDeg in all but the lowest HbA1c category. In DUAL I, insulin dose and hypoglycaemia rate were lower across all baseline HbA1c categories for IDegLira versus IDeg, while hypoglycaemia was higher with IDegLira than liraglutide, irrespective of baseline HbA1c. In DUAL II, insulin dose and hypoglycaemia rate were similar with IDegLira and IDeg (maximum dose limited to 50 U) independent of baseline HbA1c. The reduction in HbA1c with IDegLira was independent of disease duration and previous insulin dose but varied depending on pre‐trial OAD treatment. CONCLUSIONS: IDegLira effectively lowered HbA1c across a range of measures, implying suitability for patients with either early or advanced T2D

Effect of sotagliflozin as an adjunct to insulin therapy on blood pressure and arterial stiffness in adults with type 1 diabetes: A post hoc pooled analysis of inTandem1 and inTandem2

Objective: Evaluate the effect of sotagliflozin, a dual inhibitor of sodium glucose cotransporter (SGLT) 1 and 2, on arterial stiffness in patients with type 1 diabetes (T1D) treated with sotagliflozin as adjunct to optimized insulin therapy. Methods: In this post hoc analysis, indirect markers of arterial stiffness, including pulse pressure, mean arterial pressure (MAP), and double product, were calculated using observed systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse rate at 24 weeks using data from a pooled patient population from the inTandem1 and inTandem2 randomized controlled trials (n = 1575). Results: Baseline characteristics were similar among groups. Relative to placebo at Week 24, sotagliflozin 200 mg and 400 mg reduced SBP by 2.03 mm Hg (95% CI −3.30 to −0.75; p = 0.0019) and 2.85 mm Hg (−4.12 to −1.57; p < 0.0001), respectively. DBP decreased by 1.1 and 0.9 mm Hg, MAP by 1.4 and 1.6 mm Hg, and double product by 202.5 and 221.1 bpm × mm Hg, respectively (p < 0.05 for all). No increases in heart rate were observed. Conclusion: In adults with T1D, adding sotagliflozin to insulin significantly reduced blood pressure and other markers of arterial stiffness and vascular resistance

The DURAbility of Basal versus Lispro mix 75/25 insulin Efficacy (DURABLE) Trial: Comparing the durability of lispro mix 75/25 and glargine

OBJECTIVE This study compared the durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25: 75% insulin lispro protamine suspension/25% lispro) and once-daily insulin glargine, added to oral antihyperglycemic drugs in type 2 diabetes patients

Use of Dipeptidyl Peptidase-4 Inhibitors and the Reporting of Infections: A Disproportionality Analysis in the World Health Organization VigiBase

OBJECTIVE - Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. They inactivate incretin hormones but also have many other effects throughout the body, among which are effects on the immune system. This might result in an increased infection risk. This study assessed the association between use of DPP-4 inhibitors and the reporting of infections. RESEARCH DESIGN AND METHODS - A nested case-control was conducted using VigiBase, the World Health Organization-Adverse Drug Reactions (WHO-ADR) database. The base cohort consisted of ADRs for antidiabetic drugs (Anatomical Therapeutic Chemical code A10). Cases were defined as ADRs of infection according to the Medical Dictionary for Regulatory Activities (MedDRA) classification system. All other ADRs were considered controls. Reporting odds ratios (RORs) were calculated to estimate the strength of the association between different classes of antidiabetic drugs and the reporting of infections. RESULTS - We identified 305,415 suspected ADRs involving antidiabetic drugs in 106,469 case reports, of which 8,083 involved DPP-4 inhibitors monotherapy. Overall, the reporting of infections was higher for patients using DPP-4 inhibitors compared with users of biguanides (ROR 2.3 [95% CI 1.9-2.7]). Reporting of upper respiratory tract infections (ROR 12.3 [95% CI 8.6-17.5]) was significantly associated with use of DPP-4 inhibitors. CONCLUSIONS - This study indicates an increased reporting of infections, in particular upper respiratory tract infections, for users of DPP-4 inhibitors compared with users of other antidiabetic drugs. However, the limitations of spontaneous reporting systems (e.g., underreporting, the Weber-effect, reporting bias) should be taken into account. Therefore, further research is needed to evaluate this suspicion and the underlying mechanism

A pilot study evaluating the use of ABCD2 score in pre-hospital assessment of patients with suspected transient ischaemic attack: experience and lessons learned

Background: Suspected transient ischaemic attack (TIA) is a common presentation to emergency medical services (EMS) in the United Kingdom (UK). Several EMS systems have adopted the ABCD2 score to aid pre-hospital risk stratification and decision-making on patient disposition, such as direct referral to an Emergency Department or specialist TIA clinic. However, the ABCD2 score, developed for hospital use, has not been validated for use in the pre-hospital context of EMS care. Methods: We conducted a pilot study to assess eligibility criteria, recruitment rates, protocol compliance, consent and follow-up procedures to inform the development of a definitive study to validate the ABCD2 tool in pre-hospital evaluation of patients with suspected TIA. Results: From 1st May–1st September 2013, nine patients with an EMS suspected diagnosis of TIA had the TIA diagnosis later confirmed by a specialist from five participating sites. This recruitment rate is comparable to stroke trials in the EMS setting. Bureaucratic obstacles and duplication of approval processes across participating sites took 13 months to resolve before recruitment commenced. Due to the initial difficulty in recruitment, a substantial amendment was approved to modify inclusion criteria, allowing patients with atrial fibrillation and/or taking anticoagulant therapy to participate in the study. Conclusions: It is possible to identify, recruit and follow up patients with suspected TIA in the EMS setting. Training large numbers of EMS staff is required as exposure to TIA patients is infrequent. Significant insight was gained into the complexity of NHS research governance mechanisms in the UK. This knowledge will facilitate the planning of a future adequately powered study to validate the ABCD2 tool in a pre-hospital setting

One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial

AimsTo confirm, in a 26‐week extension study, the sustained efficacy and safety of a fixed combination of insulin degludec and liraglutide (IDegLira) compared with either insulin degludec or liraglutide alone, in patients with type 2 diabetes.MethodsInsulin‐naïve adults with type 2 diabetes randomized to once‐daily IDegLira, insulin degludec or liraglutide, in addition to metformin ± pioglitazone, continued their allocated treatment in this preplanned 26‐week extension of the DUAL I trial.ResultsA total of 78.8% of patients (1311/1663) continued into the extension phase. The mean glycated haemoglobin (HbA1c) concentration at 52 weeks was reduced from baseline by 1.84% (20.2 mmol/mol) for the IDegLira group, 1.40% (15.3 mmol/mol) for the insulin degludec group and 1.21% (13.2 mmol/mol) for the liraglutide group. Of the patients on IDegLira, 78% achieved an HbA1c of <7% (53 mmol/mol) versus 63% of the patients on insulin degludec and 57% of those on liraglutide. The mean fasting plasma glucose concentration at the end of the trial was similar for IDegLira (5.7 mmol/l) and insulin degludec (6.0 mmol/l), but higher for liraglutide (7.3 mmol/l). At 52 weeks, the daily insulin dose was 37% lower with IDegLira (39 units) than with insulin degludec (62 units). IDegLira was associated with a significantly greater decrease in body weight (estimated treatment difference, −2.80 kg, p < 0.0001) and a 37% lower rate of hypoglycaemia compared with insulin degludec. Overall, all treatments were well tolerated and no new adverse events or tolerability issues were observed for IDegLira.ConclusionsThese 12‐month data, derived from a 26‐week extension of the DUAL I trial, confirm the initial 26‐week main phase results and the sustainability of the benefits of IDegLira compared with its components in glycaemic efficacy, safety and tolerability

Measurement of the Bovine Pancreatic Trypsin Inhibitors by Radioimmunoassay

Bovine pancreas contains two polypeptide trypsin inhibitors that are not homologous and differ in their inhibitory activity towards chymotrypsin, kallikrein, elastase, and other serine proteinases. The Kunitz inhibitor and the Kazal inhibitor are present in approximately equimolar concentrations in bovine pancreatic tissue, yet only the Kazal inhibitor is detectable in the pancreatic juice. The Kazal inhibitor has been named the pancreatic secretory trypsin inhibitor, PSTI because its concentration in the pancreatic juice parallels that of the exocrine secretory proteins. The Kunitz inhibitor is considered the intracellular inhibitor, however, no direct information is available concerning the intracellular localization of these inhibitors in the pancreas. The preparation of /sup 125/I-labeled derivatives of Kazal and Kunitz inhibitors by the lactoperoxidase method and a radioimmunoassay for each inhibitor are described. (auth