Efficacy and Safety of Taspoglutide Versus Sitagliptin for Type 2 Diabetes Mellitus (T-Emerge 4 Trial)

INTRODUCTION: The efficacy and safety of taspoglutide, a long-acting human glucagon-like peptide-1 analog, were compared with sitagliptin or placebo, as adjunct to metformin, in patients with inadequately controlled type 2 diabetes. METHODS: In this randomized, double-blind, double-dummy, parallel-group trial, patients were randomized to taspoglutide 10 mg once weekly (QW), 20 mg QW, 100 mg sitagliptin once daily (QD), or placebo for 24 weeks, followed by 28-week short-term and 104-week long-term extension periods. The primary endpoint was change in glycosylated hemoglobin (HbA(1c)) after 24 weeks. RESULTS: In this study, 666 patients (baseline HbA(1c), 7.96% [SD, 0.87]; fasting plasma glucose, 9.61 mmol/L [2.56]; body weight, 92.4 kg [19.3]) were randomized to taspoglutide 10 mg QW (n = 190), 20 mg QW (n = 198), 100 mg sitagliptin QD (n = 185), or placebo (n = 93) for 24 weeks. After 24 weeks, least squares mean (SE) HbA(1c) reductions were greater with taspoglutide 10 mg (−1.23% [0.06]) and 20 mg (−1.30% [0.06]) versus sitagliptin (−0.89% [0.06]) or placebo (−0.10% [0.08]). Mean treatment differences with taspoglutide 10 mg and 20 mg were −0.34 (95% confidence intervals [CI]: −0.49, −0.19) and −0.41 (−0.56, −0.26) versus sitagliptin; and −1.13 (−1.31, −0.95) and −1.20 (−1.38, −1.02) versus placebo. Weight loss was greater with taspoglutide 10 mg (−1.8 kg [0.3]) and 20 mg (−2.6 kg [0.3]) than sitagliptin (−0.9 kg [0.3]) or placebo (−0.5 kg [0.4]). Effects on HbA(1c) and weight loss continued through 52 weeks of treatment. No cases of severe hypoglycemia occurred with any active treatment. Gastrointestinal adverse events, and allergic and injection-site reactions were higher in the taspoglutide groups, causing higher discontinuation rates. Anti-taspoglutide antibodies were confirmed in 46% of patients. CONCLUSION: Taspoglutide demonstrated better efficacy on glycemic control and weight loss than sitagliptin, but a high incidence of adverse events led to high discontinuation rates. The safety profile of taspoglutide in this trial was similar to other trials in the clinical program, and led to the discontinuation of dosing

Zastosowanie leku XENical w zapobieganiu cukrzycy u osób z otyłością — badanie XENDOS. Badanie randomizowane z zastosowaniem orlistatu jako dodatkowego, oprócz zmian stylu życia, czynnika zapobiegania cukrzycy typu 2 u pacjentów z otyłością

INTRODUCTION. It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients. MATERIAL AND METHODS. In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI &#8805; 30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. RESULTS. Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years&#8217; treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001). CONCLUSIONS. Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT and or NGT.WSTĘP. Ryzyko rozwoju cukrzycy typu 2 wiąże się ściśle z obecnością i czasem trwania nadwagi oraz otyłości. Wpływ wprowadzenia zmian stylu życia na zmniejszenie częstości cukrzycy typu 2 potwierdzono we wcześniejszych badaniach. Wysunięto hipotezę, według której zastosowanie dodatkowego czynnika powodującego zmniejszenie masy ciała u chorych, którym udało się ten cel częściowo osiągnąć pod wpływem zmiany stylu życia, pozwala uzyskać jeszcze lepsze efekty, a w konsekwencji prowadzi do dalszej redukcji częstości cukrzycy typu 2 u pacjentów z otyłością. MATERIAŁ I METODY. Do trwającego 4 lata, prospektywnego, randomizowanego badania, przeprowadzonego metodą podwójnie ślepej próby zakwalifikowano 3305 pacjentów, których losowo podzielono na dwie grupy. W pierwszej grupie, obok wprowadzenia zmian stylu życia, pacjentom podawano 3 razy na dobę orlistat w dawce 120 mg, a w drugiej &#8212; placebo. Wskaźnik masy ciała (BMI, body mass index) uczestników badania był większy lub równy 30 kg/m2, stężenie glukozy było prawidłowe (79%) lub rozpoznawano upośledzoną tolerancję glukozy (IGT, impaired glucose tolerance) (21%). Jako główne kryterium oceny badania przyjęto czas do wystąpienia cukrzycy typu 2 oraz zmianę masy ciała. Przeprowadzono analizę według pierwotnej intencji leczenia (intention to treat). WYNIKI. Leczenie ukończyło 52% badanych otrzymujących orlistat i 34% przyjmujących placebo (p < 0,0001). Po 4 latach terapii skumulowane ryzyko wystąpienia cukrzycy w grupie otrzymującej placebo wyniosło 9%, natomiast w grupie przyjmującej orlistat &#8212; 6,2%, co oznacza redukcję ryzyka o 37,3% (p = 0,0032). Na podstawie analizy uzyskanych danych stwierdzono, że efekt prewencyjny wynikał z różnic wśród pacjentów z upośledzoną tolerancją glukozy. Średnia redukcja masy ciała po 4 latach obserwacji była znacząco wyższa w grupie leczonej orlistatem (5,8 vs. 3,0 kg w grupie otrzymującej placebo; p < 0,001) oraz podobna u pacjentów otrzymujących orlistat z wyjściową upośledzoną (5,7 kg) lub prawidłową tolerancją glukozy (NGT, normal glucose tolerance) (5,8 kg). W drugiej analizie, w której uwzględniono zmiany masy ciała u osób wyłączonych z badania, również wykazano większą redukcję masy ciała w grupie leczonej orlistatem (3,6 vs. 1,4 kg; p < 0,001). WNIOSKI. W badaniu przeprowadzonym w reprezentatywnej populacji osób z otyłością wykazano, że w porównaniu z postępowaniem opartym wyłącznie na zmianie stylu życia, dodanie orlistatu spowodowało większy spadek częstości cukrzycy typu 2 oraz większą redukcję masy ciała w okresie 4 lat. Różnica w częstości cukrzycy była widoczna tylko w podgrupie z IGT, zmniejszenie masy ciała było podobne zarówno w podgrupie z IGT, jak i z NGT

Why are aggregate equity payouts pro-cyclical?

We use two general equilibrium models to explain why changes in the external economic environment result in pro-cyclical aggregate dividend payout behavior. Both models that we consider endogenize low elasticity of investment. The first model incorporates capital adjustment costs, while the second one assumes that risk-averse managers maximize their own objective function rather than shareholder wealth. We show that, while both models generate pro-cyclical aggregate dividends, a feature consistent with the observed business-cycle pattern of payouts from well-diversified portfolios, the second model provides a more likely explanation for this effect. Our findings emphasize the importance of incorporating agency conflicts when considering the relationship between the external economic environment and the financial behavior of businesses

Does patenting help high-tech start-ups?

Abstract: Using data on all high- and medium-tech start-ups in the UK in 2000, this paper assesses the effect associated with a firm's decision to patent on a firm's subsequent growth between 2001 and 2005. We propose a new approach to addressing well known issues challenging identification of any patent effect: firm heterogeneity, simultaneity between firm performance and patenting, and sample selection. Our findings suggest that patentees have higher asset growth than non-patentees of between 8% and 27% per annum. © 2011 Elsevier B.V. All rights reserved

Aggregate dividends and consumption smoothing

We show that net equity payouts from the corporate sector play a crucial role in helping individuals manage their consumption path across the business cycle. In particular, we show that, as investors' desire to smooth consumption increases, optimal aggregate dividends become both more volatile and more counter-cyclical to help counterbalance pro-cyclical labor income. These findings are robust to whether or not agency conflicts exist in the economy

The L&E of Intellectual Property – Do we get maximum innovation with the current regime?

Innovation is crucial to economic growth – the essential path for lifting much of the world population out of dire poverty and for maintaining the living standard of those who already have. To stimulate innovation, the legal system has to support the means through which innovators seek to get rewarded for their efforts. Amongst these means, some, such as the first mover advantage or 'lead time,' are not directly legal; but secrets and intellectual property rights are legal institutions supported for the specific purpose of stimulating innovation. Whilst the protection of secrets has not changed very much over recent years, intellectual property (or IP) has. IP borrows some features from ordinary property rights, but is also distinct, in that, unlike physical goods, information, the object of IP, is not inherently scarce; indeed as information and communication technologies expand, the creation and distribution of information is becoming ever cheaper and in many circumstances abundant, so that selection is of the essence ('on the internet, point of view is everything'). Where rights on information extend too far, their monopolising effect may hamper innovation. The paper investigates the underlying structure of IP rights and surveys what we know empirically about the incentive effects of IP as about industries that flourish without formal IP