Characteristics of long-term randomised controlled trials of thiazolidinedione use included in the analysis of pneumonia and lower respiratory tract infection adverse events
| Source | Location | Participants | Inclusions | Exclusions | Duration (years) | Drug and daily dose | Male (%) | Age, mean (SD) (years) | Median HbA1C, (SD) |
| Rosiglitazone | |||||||||
| Kahn et al (2006)17 GSK 49653/04818 | Multicentre, North America and Europe | Type 2 diabetes | Diagnosed in last 3 years and treated with diet and exercise | Hepatic disease, renal impairment, anaemia, lactic acidosis or UA or CHF, uncontrolled HTN, requiring steroid | 4 | Rosiglitazone 8 mg | 55.7 | 56.3 (10) | 7.36 (0.92) |
| Glibenclamide 15 mg | 58.0 | 56.4 (10.2) | 7.36 (0.93) | ||||||
| Metformin 2000 mg | 59.4 | 56.9 (9.9) | 7.35 (0.93) | ||||||
| Gerstein et al (2010)19 GSK AVD 10052120 | Multicentre, Europe, Asia and America | Type 2 diabetes | >1 atherosclerotic plaque with 1–2 OHAs | MI, CABG, CHF, renal and liver disease | 1.5 | Rosiglitazone 4 mg | 70.4 | 61.8 (8.38) | 7.10 (0.84) |
| Glipizide 5 mg | 65.6 | 60.2 (9.05) | 7.20 (0.91) | ||||||
| GSK 049653/020 (2004)21 | Multicentre, Europe | Type 2 diabetes | C- peptide level>0.80 ng/ml and FPG>126 mg/dl and <270 mg/dl | Diabetic complications, serious renal, hepatic or haematological impairment | 1 | Rosiglitazone 4 mg | 68.2 | 60.4 (8.23) | 8.07 (1.29) |
| Rosiglitazone 8 mg | 57.7 | 60.6 (9.27) | 8.21 (1.44) | ||||||
| Glibenclamide | 70.4 | 60.1 (8.34) | 8.15 (1.26) | ||||||
| Dargie et al (2007)22 GSK 49653/21123 | Multicentre, Europe | Type 2 diabetes | Symptomatic CHF and FPG>126 mg/dl or <216 mg/dl | BMI>35 kg/m2, significant hepatic, renal disease or anaemia | 1 | Rosiglitazone 4 mg | 84.3 | 64.3 (8.8) | 7.7 (1.3) |
| Placebo | 79 | 63.9 (8.6) | 7.8 (1.3) | ||||||
| Hedblad et al (2007)24 GSK 49653/33425 | Single centre, Sweden | Type2 diabetes insulin resistance | HOMA IR>1.80 for women and >2.12 for men | UA, CHF, required insulin, history of ketoacidosis, 2 or more OHAs | 1 | Rosiglitazone 4 mg | 44.8 | 67.7 (5.3) | 6.31 (0.76) |
| Placebo | 47.6 | 67.3 (6.3) | 6.28 (0.78) | ||||||
| GSK 049653/35126 | Single centre, UK | Type 2 diabetes | HBAIC <10%, treated with OHA, vascular disease | 2 or more OHAs or required insulin | 1 | Rosiglitazone 8 mg | 77.8 | 62.2 (8.2) | NA |
| Placebo | 79.3 | 65.6 (6.1) | NA | ||||||
| GSK AVM 100264 (2006)27 | Multicentre, Europe, Mexico | Type 2 diabetes | HBAIC >7 and <10 on Met | OHAs other than metformin, renal, hepatic disease or CHF NYHA I–IV | 1 | Rosiglitazone 4–8 mg | 52.7 | 58.5 (9.6) | 8.04 (0.89) |
| Sulfonylurea | 52.5 | 59.3 (9.2) | 7.99 (0.96) | ||||||
| Home et al (2009)6 | 364 centres in Europe and Australasia | Type 2 diabetes | BMI>25 kg/m2 on Met or SU with HBAIC 7–9% | Hospitalisation for major CV event 3 months prior, planned intervention, CHF | 5.5 | Rosiglitazone 4–8 mg (+Met) | 53.8 | 57.0 (8.0) | 7.8 (0.7) |
| Rosiglitazone 4–8 mg (+SU) | 49 | 59.8 (8.3) | 8.0(0.7) | ||||||
| Metformin 2550 mg (+SU) | 52.9 | 57.2 (8.1) | 7.8 (0.7) | ||||||
| Glibenclamide 15 mg (+Met) | 50.6 | 59.7 (8.2) | 8.0 (0.7) | ||||||
| Pioglitazone | |||||||||
| Dormandy et al (2005)11 | Multicentre | Type 2 diabetes | HBAIC>6.5% treated with diet or oral agents and extensive macrovascular disease | Type 1 diabetes, coronary or peripheral revascularisation, NHYA II and above CHF, haemodialysis or elevated liver enzymes | 3.5 | Pioglitazone15–45 mg | 67 | 61.9 (7.6) | 7.8 (NA) |
| Placebo | 66 | 61.6 (7.8) | 7.9 (NA) | ||||||
| Schernthaner et al (2004)29 * | 167 centres in 12 European countries | Type 2 diabetes | Poorly controlled type 2 diabetes with HBAIC between 7.5% and 11%, age >65 | Type 1 diabetes, ketoacidosis, MI, TIA or stroke in last 6 months, NYHA I–IV CHF, cancer or substance abuse | 1 | Pioglitazone 30–45 mg | 52.1 | 69.5 (2.93) | 8.58 (0.93) |
| Metformin 850 mg once a day to three times a day | 44.7 | 69.1 (2.92) | 8.83 (1.01) | ||||||
| Charbonnel et al (2005)30 * | 206 centres in Europe | Type 2 diabetes | Poorly controlled type 2 diabetes with HBAIC between 7.5% and 11%, age >65 | Type 1 diabetes, ketoacidosis, MI, TIA or stroke in last 6 months, NYHA I–IV CHF, cancer or substance abuse | 1 | Pioglitazone 30–45 mg | 52.1 | 69.5 (2.93) | 8.58 (0.95) |
| Gliclazide 80–160 mg twice a day | 56.3 | 69.5 (2.85) | 8.58 (0.95) | ||||||
| Hanefeld et al (2004)31 * | 91 centres in Europe and Canada | Type 2 diabetes | Poorly controlled type 2 diabetes with HBAIC between 7.5% and 11%, age >65 | Type 1 diabetes, ketoacidosis, MI, TIA or stroke in last 6 months, NYHA I–IV CHF cancer or substance abuse | 1 | Pioglitazone 14–45 mg | 53.3 | 69.8 (2.7) | 8.79 (0.79) |
| Metformin 850 mg once a day to three times a day | 49.5 | 69.3 (3.12) | 8.75 (1.01) | ||||||
| Matthews et al (2005)32 * | 75 centres in Europe and Australia | Type 2 diabetes | Poorly controlled type 2 diabetes with glycated haemoglobin between 7.5% and 11%, age >65 | Type 1 diabetes, ketoacidosis, MI, TIA or stroke in last 6 months, NYHA I–IV CHF, cancer or substance abuse | 1 | Pioglitazone 15–45 mg | 50.8 | 69.5 (2.79) | 8.58 (0.97) |
| Gliclazide 80–160 mg twice a day | 33.3 | 69.3 (2.75) | 8.50 (0.82) | ||||||
↵* Post hoc pooled safety analysis on a subgroup of older participants from four randomised controlled trials (Rajagopalan et al 2006).28
BMI, body mass index; CABG, coronary artery bypass graft; CHF, congestive heart failure; CV, cardiovascular; FPG, fasting plasma glucose; GSK, GlaxoSmithKline; HOMA IR, homeostatic model assessment insulin resistance; HBAIC, glycated haemoglobin; HTN, hypertension; Met, metformin; MI, myocardial infarction; NA, not available; NYHA, New York Heart Association; OHA, oral hypoglycemic agents; TIA, transient ischaemic attack; UA, unstable angina; SU, sulfonylurea.