OBJECTIVE: To evaluate the efficacy of pioglitazone for the prevention of macrovascular outcomes in Japanese patients with type 2 diabetes, without a recent history of macrovascular morbidity. RESEARCH DESIGN AND METHODS: This 2.5-4 year, prospective, randomized, open-label, blinded-endpoint study was conducted in 20 Japanese centers. Patients received pioglitazone +/- other oral glucose-lowering drugs (excluding another thiazolidinedione) [n = 293] or oral glucose-lowering drugs excluding thiazolidinediones (n = 294). Treatment was adjusted to achieve HbA(1c) < 6.5%. The primary endpoint was the time to onset of a macrovascular event. RESULTS: Pioglitazone delayed the time to onset of macrovascular events and was associated with a lower cumulative incidence of such events (3.56% vs. 4.49% for controls). Neither finding achieved statistical significance. This was likely because of the type of patient included in the study (i.e. no recent history of cardiovascular events) and the high use of concomitant anti-diabetic agents. Reductions in HbA(1c), fasting blood glucose and fasting blood insulin levels, and an increase in HDL-C were significantly greater with pioglitazone throughout most of the study (p < 0.05). Fewer patients in the pioglitazone group commenced permanent treatment with insulin (3.3% vs. 13.7% in the control group). Adverse events were reported by 97.6% of the pioglitazone group and 96.9% of the control group (serious adverse events, including deaths, were 20.1 vs. 22.2%, respectively). The only notable difference between the two groups was a higher incidence of edema in the pioglitazone group. The main limitation of this study was that too few patients were included to identify statistically significant differences in the primary endpoint. CONCLUSIONS: Pioglitazone produced good glycemic control in Japanese patients with type 2 diabetes, and significantly fewer patients treated with pioglitazone needed long-term insulin therapy. These changes were associated with a trend towards delayed onset of macrovascular events. CLINICAL TRIAL REGISTRATION: UMIN000001363.
RCT Entities:
OBJECTIVE: To evaluate the efficacy of pioglitazone for the prevention of macrovascular outcomes in Japanese patients with type 2 diabetes, without a recent history of macrovascular morbidity. RESEARCH DESIGN AND METHODS: This 2.5-4 year, prospective, randomized, open-label, blinded-endpoint study was conducted in 20 Japanese centers. Patients received pioglitazone +/- other oral glucose-lowering drugs (excluding another thiazolidinedione) [n = 293] or oral glucose-lowering drugs excluding thiazolidinediones (n = 294). Treatment was adjusted to achieve HbA(1c) < 6.5%. The primary endpoint was the time to onset of a macrovascular event. RESULTS:Pioglitazone delayed the time to onset of macrovascular events and was associated with a lower cumulative incidence of such events (3.56% vs. 4.49% for controls). Neither finding achieved statistical significance. This was likely because of the type of patient included in the study (i.e. no recent history of cardiovascular events) and the high use of concomitant anti-diabetic agents. Reductions in HbA(1c), fasting blood glucose and fasting blood insulin levels, and an increase in HDL-C were significantly greater with pioglitazone throughout most of the study (p < 0.05). Fewer patients in the pioglitazone group commenced permanent treatment with insulin (3.3% vs. 13.7% in the control group). Adverse events were reported by 97.6% of the pioglitazone group and 96.9% of the control group (serious adverse events, including deaths, were 20.1 vs. 22.2%, respectively). The only notable difference between the two groups was a higher incidence of edema in the pioglitazone group. The main limitation of this study was that too few patients were included to identify statistically significant differences in the primary endpoint. CONCLUSIONS:Pioglitazone produced good glycemic control in Japanese patients with type 2 diabetes, and significantly fewer patients treated with pioglitazone needed long-term insulin therapy. These changes were associated with a trend towards delayed onset of macrovascular events. CLINICAL TRIAL REGISTRATION: UMIN000001363.
Authors: Peter Willeit; Lena Tschiderer; Michael J Sweeting; Simon G Thompson; Matthias W Lorenz; Elias Allara; Kathrin Reuber; Lisa Seekircher; Lu Gao; Ximing Liao; Eva Lonn; Hertzel C Gerstein; Salim Yusuf; Frank P Brouwers; Folkert W Asselbergs; Wiek van Gilst; Sigmund A Anderssen; Diederick E Grobbee; John J P Kastelein; Frank L J Visseren; George Ntaios; Apostolos I Hatzitolios; Christos Savopoulos; Pythia T Nieuwkerk; Erik Stroes; Matthew Walters; Peter Higgins; Jesse Dawson; Paolo Gresele; Giuseppe Guglielmini; Rino Migliacci; Marat Ezhov; Maya Safarova; Tatyana Balakhonova; Eiichi Sato; Mayuko Amaha; Tsukasa Nakamura; Kostas Kapellas; Lisa M Jamieson; Michael Skilton; James A Blumenthal; Alan Hinderliter; Andrew Sherwood; Patrick J Smith; Michiel A van Agtmael; Peter Reiss; Marit G A van Vonderen; Stefan Kiechl; Gerhard Klingenschmid; Matthias Sitzer; Coen D A Stehouwer; Heiko Uthoff; Zhi-Yong Zou; Ana R Cunha; Mario F Neves; Miles D Witham; Hyun-Woong Park; Moo-Sik Lee; Jang-Ho Bae; Enrique Bernal; Kristian Wachtell; Sverre E Kjeldsen; Michael H Olsen; David Preiss; Naveed Sattar; Edith Beishuizen; Menno V Huisman; Mark A Espeland; Caroline Schmidt; Stefan Agewall; Ercan Ok; Gülay Aşçi; Eric de Groot; Muriel P C Grooteman; Peter J Blankestijn; Michiel L Bots Journal: Circulation Date: 2020-06-17 Impact factor: 29.690
Authors: Suetonia C Palmer; Britta Tendal; Reem A Mustafa; Per Olav Vandvik; Sheyu Li; Qiukui Hao; David Tunnicliffe; Marinella Ruospo; Patrizia Natale; Valeria Saglimbene; Antonio Nicolucci; David W Johnson; Marcello Tonelli; Maria Chiara Rossi; Sunil V Badve; Yeoungjee Cho; Annie-Claire Nadeau-Fredette; Michael Burke; Labib I Faruque; Anita Lloyd; Nasreen Ahmad; Yuanchen Liu; Sophanny Tiv; Tanya Millard; Lucia Gagliardi; Nithin Kolanu; Rahul D Barmanray; Rita McMorrow; Ana Karina Raygoza Cortez; Heath White; Xiangyang Chen; Xu Zhou; Jiali Liu; Andrea Flores Rodríguez; Alejandro Díaz González-Colmenero; Yang Wang; Ling Li; Surya Sutanto; Ricardo Cesar Solis; Fernando Díaz González-Colmenero; René Rodriguez-Gutierrez; Michael Walsh; Gordon Guyatt; Giovanni F M Strippoli Journal: BMJ Date: 2021-01-13