A comparison of all-cause mortality with pioglitazone and insulin in type 2 diabetes: an expanded analysis from a retrospective cohort study

Jiao, Yang; Vallarino, Carlos; Bron, Morgan; Pérez, Alfonso; Liang, Huifang; Joseph, Guiandre; Yu, Su

doi:10.1185/03007995.2014.941054

Cited by 22 publications

(18 citation statements)

References 25 publications

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“…There were 597 deaths in the study cohort over an average 4.5 years of follow-up time. Yang et al ’s observational study17 comparing first time users of insulin or pioglitazone in a US claims database also found a statistically significant decrease in risk of all-cause mortality in the pioglitazone cohort compared with the insulin cohort.…”

Section: Discussionmentioning

confidence: 94%

“…Fewer deaths contributed to the primary and secondary endpoint in the pioglitazone arm than the placebo arm. An observational study using US claims data found a significantly lower risk of all-cause mortality in patients with T2DM prescribed pioglitazone compared with insulin (HR 0.33, 95% CI 0.31 to 0.36) 17. More recently, a cohort study using data from a UK primary care database showed a decreased risk of all-cause mortality (HR 0.82, 95% CI 0.77 to 0.88), heart failure (HR 0.86, 95% CI 0.78 to 0.95) and cardiovascular (CV) disease (HR 0.94, 95% CI 0.88 to 1.00) with use of glitazones in T2DM compared with non-use of these agents 18.…”

Section: Introductionmentioning

confidence: 99%

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Pioglitazone and risk of mortality in patients with type 2 diabetes: results from a European multidatabase cohort study

Strongman

Korhonen²,

Williams

et al. 2017

BMJ Open Diab Res Care

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ObjectivesEstimate and compare the risk of mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression.DesignRetrospective cohort study.SettingPooled analysis of clinical data collected from primary and/or secondary care settings in four European countries: Finland, The Netherlands, Sweden and the UK .Participants56 337 patients with type 2 diabetes mellitus first prescribed pioglitazone between 2000 and 2011, and 56 337 patients never prescribed pioglitazone matched by treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry using exact and propensity score matching. Patients were followed-up for a mean of 2.90 (SD 2.21) and 2.83 (SD 2.37) years in the pioglitazone-exposed and non-pioglitazone-exposed groups, respectively.OutcomesAll-cause mortality ascertained from clinical or registry data. Mortality was a planned secondary outcome in a study primarily studying the association of pioglitazone use with bladder cancer risk.ResultsThe crude overall mortality rate per 10 000 patient years was 206 (95% CI 199 to 213) in the pioglitazone-exposed group and 448 (95% CI 438 to 458) in the non-pioglitazone-exposed group. The crude HR comparing pioglitazone to alternative antidiabetic exposure was 0.46 (95% CI 0.45 to 0.48). This reduced in magnitude to 0.67 (95% CI 0.64 to 0.70) following further adjustment for matching variables, propensity scores, age, gender and time-dependent variables representing use of alternative antidiabetic drugs.ConclusionsIn this large observational cohort study of patients with type 2 diabetes, pioglitazone exposure was associated with a statistically significant decrease in the risk of all-cause mortality across four European countries. Results should be interpreted with caution due to the potential for residual confounding.Protocol registrationEuropean Network of Centres for Pharmacoepidemiology and Pharmacovigilance.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Pioglitazone and risk of mortality in patients with type 2 diabetes: results from a European multidatabase cohort study

Strongman

Korhonen²,

Williams

et al. 2017

BMJ Open Diab Res Care

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“…Note that patients receiving any other anti-diabetic medications, including TZDs, were excluded from the study, and thus the likely effect of TZDs to reduce insulin requirements was not evaluated. Another very recent industry-funded retrospective cohort study did compare TZD to insulin and found that patients started on pioglitazone from 2000–2010 had a remarkably significant 67% lower all-cause mortality than those started on insulin (Yang et al, 2014), though this study was unable to adjust for glycemic control.…”

Section: Why Does It Matter? the Case For Reducing Insulin Levelsmentioning

confidence: 90%

Thiazolidinediones and the Promise of Insulin Sensitization in Type 2 Diabetes

2014

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Type 2 diabetes is caused by insulin resistance coupled with an inability to produce enough insulin to control blood glucose, and thiazolidinediones (TZDs) are the only current antidiabetic agents that function primarily by increasing insulin sensitivity. However, despite clear benefits in glycemic control, this class of drugs has recently fallen into disuse due to concerns over side effects and adverse events. Here we review the clinical data and attempt to balance the benefits and risks of TZD therapy. We also examine potential mechanisms of action for the beneficial and harmful effects of TZDs, mainly via agonism of the nuclear receptor PPARγ. Based on critical appraisal of both preclinical and clinical studies, we discuss the prospect of harnessing the insulin sensitizing effects of PPARγ for more effective, safe, and potentially personalized treatments of type 2 diabetes.

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“…The combination of metformin and the peroxisome proliferator-activated receptor (PPAR) γ agonist pioglitazone, a drug from the thiazolidinedione family, provided superior clinical outcomes to metformin alone [ 5 ]. In spite of the beneficial effects of thiazolidinediones on glycemic control, insulin sensitivity, inflammation and oxidative stress [ 2 , 4 , 5 ], as well as their triacylglycerol-lowering effect in both humans [ 5 ] and mice [ 6 , 7 ], clinical use of pioglitazone has declined recently due to the risk of its side-effects (reviewed in [ 1 , 8 ]). However, this risk could be outweighed by the benefits of pioglitazone in prevention of cardiovascular disease [ 9 ], the leading cause of death in patients with T2D [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, this risk could be outweighed by the benefits of pioglitazone in prevention of cardiovascular disease [ 9 ], the leading cause of death in patients with T2D [ 10 ]. Indeed, pioglitazone is associated with a relatively low risk of all-cause mortality (reviewed in [ 8 ]).…”

Section: Introductionmentioning

confidence: 99%

Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism

et al. 2015

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BackgroundThe marine n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to improve treatment of type 2 diabetic (T2D) patients remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA + DHA and the insulin-sensitizing drug pioglitazone in overweight/obese T2D patients already treated with metformin.MethodsIn a parallel-group, four-arm, randomized trial, 69 patients (66 % men) were assigned to 24-week-intervention using: (i) corn oil (5 g/day; Placebo), (ii) pioglitazone (15 mg/day; Pio), (iii) EPA + DHA concentrate (5 g/day, containing ~2.8 g EPA + DHA; Omega-3), or (iv) pioglitazone and EPA + DHA concentrate (Pio& Omega-3). Data from 60 patients were used for the final evaluation. At baseline and after intervention, various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures, EPA + DHA content in serum phospholipids was evaluated using shotgun lipidomics and mass spectrometry, and hyperinsulinemic-euglycemic clamp and meal test were also performed. Indirect calorimetry was conducted after the intervention. Primary endpoints were changes from baseline in insulin sensitivity evaluated using hyperinsulinemic-euglycemic clamp and in serum triacylglycerol concentrations in fasting state. Secondary endpoints included changes in fasting glycemia and glycated hemoglobin (HbA1c), changes in postprandial glucose, free fatty acid and triacylglycerol concentrations, metabolic flexibility assessed by indirect calorimetry, and inflammatory markers.ResultsOmega-3 and Pio& Omega-3 increased EPA + DHA content in serum phospholipids. Pio and Pio& Omega-3 increased body weight and adiponectin levels. Both fasting glycemia and HbA1c were increased by Omega-3, but were unchanged by Pio& Omega-3. Insulin sensitivity was not affected by Omega-3, while it was improved by Pio& Omega-3. Fasting triacylglycerol concentrations and inflammatory markers were not significantly affected by any of the interventions. Lipid metabolism in the meal test and metabolic flexibility were additively improved by Pio& Omega-3.ConclusionBesides preventing a modest negative effect of n-3 fatty acids on glycemic control, the combination of pioglitazone and EPA + DHA can be used to improve lipid metabolism in T2D patients on stable metformin therapy.Trial registrationEudraCT number 2009-011106-42.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-015-0047-9) contains supplementary material, which is available to authorized users.

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A comparison of all-cause mortality with pioglitazone and insulin in type 2 diabetes: an expanded analysis from a retrospective cohort study

Abstract: PIO was associated with a lower risk of all-cause mortality than INS.

Cited by 22 publications

References 25 publications

Pioglitazone and risk of mortality in patients with type 2 diabetes: results from a European multidatabase cohort study

Pioglitazone and risk of mortality in patients with type 2 diabetes: results from a European multidatabase cohort study

Thiazolidinediones and the Promise of Insulin Sensitization in Type 2 Diabetes

Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism

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