Predictors of treatment response to liraglutide in type 2 diabetes in a real-world setting.

AIMS: There is an unmet need among healthcare providers to identify subgroups of patients with type 2 diabetes who are most likely to respond to treatment. METHODS: Data 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. RESULTS: Data 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. CONCLUSIONS: Glycaemic response to liraglutide is largely driven by baseline HbA1c levels and, to a lesser extent, by diabetes duration.

Efficacy, safety and acceptability of the new pen needle 33G × 4 mm. AGO 01 study.

OBJECTIVES: Adherence to insulin therapy can be threatened by pain and needle fear. This cross-over randomized non-inferiority trial evaluated a new Pic Insupen 33G × 4 mm needle vs. a 32G × 4 mm needle in terms of metabolic control, safety and acceptability in patients with diabetes treated with insulin. RESEARCH DESIGN AND METHODS: We used a centralized, permuted block randomization, stratified by center and maximum insulin dose per single injection. Subjects used the two needles in two 3 week treatment periods. The primary endpoint was the absolute percentage variation of the blood fructosamine between the two treatments (% |ΔFru|). Additional endpoints were: glycemic variability, total insulin doses, body weight, severe hypoglycemic episodes, leakage at injection sites and pain measured by visual analogue scale. Equivalent glycemic control was defined a priori as % |ΔFru| (including 95% CI) within 20%. RESULTS: Of 87 subjects randomized, 77 completed the study (median age 53.1 [IR 42.3-61.2], median BMI 24.3 Kg/m(2) [IR 21.3-28.5], median duration of insulin therapy [in months] 141.4 (IR 56.3-256.9), median baseline HbA1c 7.9% [IR 7.2-8.8]). The % |ΔFru| was 7.93% (95% CI 6.23-9.63), meeting the non-inferiority criterion. The fasting blood glucose standard deviation was 46.2 (mean 154.6) with the 33G needle and 42.8 (mean 157.3) with the 32G needle (p=0.42). Insulin daily dose and patients' weight did not show any statistically significant variation. We observed 95 episodes of symptomatic hypoglycemia with the 33G needle and 96 with the 32G needle. One episode of severe hypoglycemia was documented in the latter group. As for insulin leakage we observed 37.55 episodes per 100 patient-days with the 33G needle and 32.21 episodes per 100 patient-days with the 32G needle (p=0.31). Patients reported less pain with the 33G × 4 mm needle (p=0.05). STUDY LIMITATIONS: Study sample was mainly composed of adults with type 1 diabetes and study was not blinded. CONCLUSIONS: The 33G needle is not inferior to the 32G needle in terms of efficacy and safety, with reduced pain and no difference in insulin leakage. CLINICAL TRIAL REGISTRATION: NCT01745549.

ROSES: role of self-monitoring of blood glucose and intensive education in patients with Type 2 diabetes not receiving insulin. A pilot randomized clinical trial.

AIMS: To estimate the efficacy of a self-monitoring-based disease management strategy in patients with Type 2 diabetes treated with oral agent monotherapy. METHODS: This was an open-label, randomized, pilot study, primarily led by diabetes nurses. Patients were randomly allocated to either a self-monitoring-based disease management strategy or usual care (ratio 3:1) and followed up for 6 months. Education was centred on how to modify lifestyle according self-monitoring readings. Self-monitoring of blood glucose results were discussed during monthly telephone contact. The primary endpoint was mean change in HbA(1c) levels, estimated with an ANOVA for repeated measures. All analyses were intention to treat. RESULTS: Three diabetic clinics recruited 62 patients, of whom five were lost to follow-up. At baseline, both groups had a mean HbA(1c) value of 7.9% ± 0.6% (63 ± 6 mmol/mol). After 6 months, mean HbA(1c) reduction was 1.2 ± 0.1% (-13 ± 1 mmol/mol) in the intervention group and 0.7 ± 0.2 (-8 ± 2 mmol/mol) in the control group, with an absolute mean difference between groups of -0.5% (95% CI -0.9 to -0.0%; P = 0.04) (-5 mmol/mol, 95% CI -10 to 0). At study end, 61.9% of patients in the intervention group and 20.0% in the control group reached the target level of HbA(1c) < 7.0% (< 53 mmol/mol) (P = 0.005). Body weight reduction was significantly greater in the intervention group than in the control group (between-group absolute mean difference: -3.99 kg; 95% CI -7.26 to -0.73; P = 0.02). Therapy changes were more frequent in the control group. CONCLUSIONS: A self-monitoring disease management strategy, primarily led by diabetes nurses and allowing a timely and efficient use of self-monitoring readings, is able to improve metabolic control, primarily through lifestyle modifications leading to weight loss.

Extensive use of peripheral angioplasty, particularly infrapopliteal, in the treatment of ischaemic diabetic foot ulcers: clinical results of a multicentric study of 221 consecutive diabetic subjects.

OBJECTIVE: To evaluate the feasibility, technical effectiveness and limb salvage potential of percutaneous transluminal angioplasty (PTA), particularly infrapopliteal, in diabetic subjects with ischaemic foot ulcer. DESIGN: Intervention study with PTA in consecutive series. SETTING: Six Diabetology Foot Centres and one Cardiovascular Catheterization Laboratory in Italy. SUBJECTS: Two hundred and twenty-one consecutive diabetic subjects hospitalized for ischaemic foot ulcer. INTERVENTION: Peripheral arterial occlusive disease (PAOD) was investigated by means of foot pulses assessment, ankle-brachial-index (ABI), transcutaneous oxygen tension (TcPO2) and duplex scanning. If non-invasive parameters suggested PAOD, angiography was performed and a PTA was carried out during the same session. MAIN OUTCOME MEASURES: PTA feasibility, improvement of ABI and TcPO2, limb salvage rate, clinical recurrence. RESULTS: On angiography, two patients had stenoses which were <50% of the vessel diameter. PTA was performed in 191 (85.3%) of the 219 subjects with stenoses >50%, even when longer than 10 cm and/or multiple/calcified. In 11 patients (5.8%) PTA was performed in the proximal axis exclusively, in 81 (42.4%) patients in the infrapopliteal axis exclusively and in 99 (51.8%) in both the femoropopliteal and infrapopliteal axis. Both ABI and TcPO2 improved significantly after PTA (P < 0.0001). Clinical recurrence occurred in 14 subjects: 10 of whom underwent a second successful PTA. Of the 191 patients who underwent PTA, 10 (5.2%) underwent an above-the-ankle amputation. CONCLUSIONS: PTA, including infrapopliteal, is feasible in most diabetic subjects with ischaemic foot ulcer and is effective for foot revascularization. Clinical recurrence was infrequent and the procedure could successfully be repeated in most cases. In subjects treated successfully with PTA the above-the-ankle amputation rate was low. PTA should be considered as the revascularization treatment of first choice in all diabetic subjects with foot ulcer and PAOD.