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Background: Hymenoptera venom allergy is a potentially severe allergic reaction in the general population. The only preventative approach in these cases is venom immunotherapy (VIT), which follows different protocols. The recommended initial dose is 0.001–0.1 mcg of venom extract. However, few reports have declared the safety of 1 mcg venom as the starting dose. Methods: The study was conducted on Iranian patients with a history of anaphylaxis to venom. Skin tests confirmed hypersensitivity to honeybee, yellow jacket, and/or paper wasp from subfamily Polistes using Apis melifera, Vespula spp, and Polistes spp venom extracts, respectively. Subsequently, the patients were treated with the cluster protocol. Results: Twenty-two patients (17 males and 5 females, aged 28.3±11.8 years) were enrolled in the study. Skin prick tests and intradermal tests showed positive results for yellow jacket in 17 (77.3%) and 21 (95.4%) patients, honeybee in 14 (63.6%) and 17 (77.3%) patients, and wasp in 14 (63.6%) and 17 (77.3%) patients, respectively. Upon administering the initial dose of 1 mcg/mL, 40.9% (9 cases) of patients presented mild local reactions, including 7 with yellow jacket allergy, 5 with honeybee allergy, and 3 with wasp allergy. One patient with yellow jacket allergy had a mild systemic reaction. Patients with a positive skin test for wasp had significantly lower rate of reactions after the first dose of venom (p=0.026). Throughout the entire build-up phase, more than 90% (20 of 22) of patients experienced mild local reactions, followed by large local reactions (3 cases, 13.6%), mild systemic reactions (1 case at 1 mcg/mL dose), and moderate-to-severe systemic reactions (3 cases, 13.6%). Large local and moderate-to-severe systemic reactions were detected after injecting 50 mcg (each one case) and 100 mcg (each 2 cases) of venom extracts. Conclusion: This study recommends 1 mcg/mL of the venom extract as a safe starting dose for VIT. This accelerated protocol could successfully reduce the time and costs of therapy for patients undergoing out-patient cluster VIT.

This trial, which compared once-weekly exenatide plus usual care with usual care alone in patients with type 2 diabetes with or without previous cardiovascular disease, showed no significant between-group difference in the rates of major adverse cardiovascular events.

BACKGROUND. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration. METHODS. As a proof of concept, using a single-blind trial design, we evaluated the progress of 45 patients with moderate Parkinson's disease (PD), randomly assigned to receive subcutaneous exenatide injection for 12 months or to act as controls. Their PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), together with several nonmotor tests, at baseline, 6 months, and 12 months and after a further 2-month washout period (14 months). RESULTS. Exenatide was well tolerated, although weight loss was common and l-dopa dose failures occurred in a single patient. Single-blinded rating of the exenatide group suggested clinically relevant improvements in PD across motor and cognitive measures compared with the control group. Exenatide-treated patients had a mean improvement at 12 months on the MDS-UPDRS of 2.7 points, compared with mean decline of 2.2 points in control patients (P = 0.037). CONCLUSION. These results demonstrate a potential cost-efficient approach through which preliminary clinical data of possible biological effects are obtainable, prior to undertaking the major investment required for double-blind trials of a potential disease-modifying drug in PD. Clinicaltrials.gov NCT01174810. Cure Parkinson's Trust.

Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist. Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1·8 mg once a day (n=233) or exenatide 10 μg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA 1c). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882. Mean baseline HbA 1c for the study population was 8·2%. Liraglutide reduced mean HbA 1c significantly more than did exenatide (−1·12% [SE 0·08] vs −0·79% [0·08]; estimated treatment difference −0·33; 95% CI −0·47 to −0·18; p<0·0001) and more patients achieved a HbA 1c value of less than 7% (54% vs 43%, respectively; odds ratio 2·02; 95% CI 1·31 to 3·11; p=0·0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (−1·61 mmol/L [SE 0·20] vs −0·60 mmol/L [0·20]; estimated treatment difference −1·01 mmol/L; 95% CI −1·37 to −0·65; p<0·0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide −3·24 kg vs exenatide −2·87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0·448, p<0·0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1·93 vs 2·60 events per patient per year; rate ratio 0·55; 95% CI 0·34 to 0·88; p=0·0131; 25·5% vs 33·6% had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode. Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations. Novo Nordisk A/S.

Exenatide is an incretin mimetic that shares glucoregulatory properties with glucagon-like peptide 1 (GLP-1), and improves glycaemic control, with progressive bodyweight reductions, when administered twice a day in patients with type 2 diabetes. We compared the efficacy of a once-weekly formulation of exenatide to that of a twice daily dose. A 30-week, randomised, non-inferiority study compared a long-acting release formulation of exenatide 2 mg administered once weekly to 10 μg exenatide administered twice a day, in 295 patients with type 2 diabetes (haemoglobin A 1c [HbA 1c] 8·3% [SD 1·0], mean fasting plasma glucose 9 [SD 2] mmol/L, weight 102 [SD 20] kg, diabetes duration 6·7 [SD 5·0] years). The patients were naive to drug therapy, or on one or more oral antidiabetic agents. The primary endpoint was the change in HbA 1c at 30 weeks. This study is registered with ClinicalTrials.gov, number NCT00308139. At 30 weeks, the patients given exenatide once a week had significantly greater changes in HbA 1c than those given exenatide twice a day (−1·9 [SE 0·1%] vs −1·5 [0·1%], 95% CI −0·54% to −0·12%; p=0·0023). A significantly greater proportion of patients receiving treatment once a week versus twice a day achieved target HbA 1c levels of 7·0% or less (77% vs 61% of evaluable patients, p=0·0039). Exenatide once weekly resulted in significantly greater improvements in glycaemic control than exenatide given twice a day, with no increased risk of hypoglycaemia and similar reductions in bodyweight. Amylin Pharmaceuticals Inc and Eli Lilly and Company.

Most patients with type 2 diabetes begin pharmacotherapy with metformin, but eventually need additional treatment. We assessed the safety and efficacy of once weekly exenatide, a glucagon-like peptide 1 receptor agonist, versus maximum approved doses of the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the thiazolidinedione, pioglitazone, in patients treated with metformin. In this 26-week randomised, double-blind, double-dummy, superiority trial, patients with type 2 diabetes who had been treated with metformin, and at baseline had mean glycosylated haemoglobin (HbA 1c) of 8·5% (SD 1·1), fasting plasma glucose of 9·1 mmol/L (2·6), and weight of 88·0 kg (20·1), were enrolled and treated at 72 sites in the USA, India, and Mexico. Patients were randomly assigned to receive: 2 mg injected exenatide once weekly plus oral placebo once daily; 100 mg oral sitagliptin once daily plus injected placebo once weekly; or 45 mg oral pioglitazone once daily plus injected placebo once weekly. Primary endpoint was change in HbA 1c between baseline and week 26. Analysis was by intention to treat, for all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00637273. 170 patients were assigned to receive once weekly exenatide, 172 to receive sitagliptin, and 172 to receive pioglitazone. 491 patients received at least one dose of study drug and were included in the intention-to-treat analysis (160 on exenatide, 166 on sitagliptin, and 165 on pioglitazone). Treatment with exenatide reduced HbA 1c (least square mean −1·5%, 95% CI −1·7 to −1·4) significantly more than did sitagliptin (−0·9%, −1·1 to −0·7) or pioglitazone (−1·2%, −1·4 to −1·0). Treatment differences were −0·6% (95% CI −0·9 to −0·4, p<0·0001) for exenatide versus sitagliptin, and −0·3% (−0·6 to −0·1, p=0·0165) for exenatide versus pioglitazone. Weight loss with exenatide (−2·3 kg, 95% CI–2·9 to −1·7) was significantly greater than with sitagliptin (difference −1·5 kg, 95% CI −2·4 to −0·7, p=0·0002) or pioglitazone (difference −5·1 kg, −5·9 to −4·3, p<0·0001). No episodes of major hypoglycaemia occurred. The most frequent adverse events with exenatide and sitagliptin were nausea (n=38, 24%, and n=16, 10%, respectively) and diarrhoea (n=29, 18%, and n=16, 10%, respectively); upper-respiratory-tract infection (n=17, 10%) and peripheral oedema (n=13, 8%) were the most frequent events with pioglitazone. The goal of many clinicians who manage diabetes is to achieve optimum glucose control alongside weight loss and a minimum number of hypoglycaemic episodes. Addition of exenatide once weekly to metformin achieved this goal more often than did addition of maximum daily doses of either sitagliptin or pioglitazone. Amylin Pharmaceuticals and Eli Lilly.

In the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) study, the safety and efficacy of 30 weeks of treatment with the glucagon-like peptide-1 receptor agonist exenatide once weekly (exenatide QW; 2 mg) was compared with exenatide BID in 295 patients with type 2 diabetes. We now report the safety and efficacy of exenatide QW in 1) patients who continued treatment for an additional 22 weeks (52 weeks total) and 2) patients who switched from exenatide BID to exenatide QW after 30 weeks. In this randomized, multicenter, comparator-controlled, open-label trial, 258 patients entered the 22-week open-ended assessment phase (n = 128 QW-only; n = 130 BID-->QW). A1C, fasting plasma glucose (FPG), body weight, blood pressure, fasting lipids, safety, and tolerability were assessed. Patients continuing exenatide QW maintained A1C improvements through 52 weeks (least squares mean -2.0% [95% CI -2.1 to -1.8%]). Patients switching from exenatide BID to exenatide QW achieved further A1C improvements; both groups exhibited the same A1C reduction and mean A1C (6.6%) at week 52. At week 52, 71 and 54% of all patients achieved A1C <7.0% and 40 mg/dl, and body weight was reduced by >4 kg after 52 weeks. Nausea occurred less frequently in this assessment period and was predominantly mild. No major hypoglycemia was observed. Exenatide QW elicited sustained improvements in glycemic control and body weight through 52 weeks of treatment. Patients switching to exenatide QW experienced further improvements in A1C and FPG, with sustained weight loss.

OBJECTIVE:--This study evaluated the effects of exenatide, a novel incretin mimetic, in hyperglycemic patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy. RESEARCH DESIGN AND METHODS--A 30-week, double-blind, placebo-controlled study was performed in 733 subjects (aged 55 ± 10 years, BMI 33.6 ± 5.7 kg/m², A1C 8.5 ± 1.0%; means ± SD) randomized to 5 [micro]g subcutaneous exenatide b.i.d. (arms A and B) or placebo for 4 weeks. Thereafter, arm A remained at 5 [micro]g b.i.d. and arm B escalated to 10 [micro]g b.i.d. Subjects continued taking their dose of metformin and were randomized to either maximally effective (MAX) or minimum recommended (MIN) doses of sulfonylurea. RESULTS:--Week 30 A1C changes from baseline (±SE) were -0.8 ± 0.1% (10 [micro]g), -0.6 ± 0.1% (5 [micro]g), and +0.2 ± 0.1% (placebo; adjusted P < 0.0001 vs. placebo), yielding placebo-adjusted reductions of -1.0% (10 [micro]g) and -0.8% (5 [micro]g). In the evaluable population, exenatide-treated subjects were more likely to achieve A1C