The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study

Azoulay, Laurent; Yin, Hui; Filion, Kristian B.; Assayag, Jonathan; Majdan, Agnieszka; Pollak, Michael; Suissa, Samy

doi:10.1136/bmj.e3645

Cited by 245 publications

(247 citation statements)

References 35 publications

(49 reference statements)

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“…Third, we repeated the primary analysis with case subjects restricted to those in whom CHF was the primary diagnosis and censoring those with CHF recorded as a secondary diagnosis. Fourth, we repeated the analysis using an alternate reference group consisting of patients currently exposed to metformin-sulfonylurea combinations, the most common treatment combination in type 2 diabetes (18,19). Fifth, we also used a reference category of current exposure to $1 oral antidiabetic drug to examine the impact of requiring current use of (and thus adherence to) two drugs in the reference group of our primary analysis.…”

Section: Sensitivity Analysesmentioning

confidence: 99%

Incretin-Based Drugs and the Risk of Congestive Heart Failure

Filion

Azoulay

et al. 2014

Diabetes Care

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OBJECTIVETo determine whether the use of incretin-based drugs, including GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, is associated with an increased risk of congestive heart failure (CHF) among patients with type 2 diabetes. RESEARCH DESIGN AND METHODSThe U.K. Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database, was used to conduct a cohort study with a nested case-control analysis among patients newly prescribed antidiabetic drugs between 1 January 2007 and 31 March 2012 and no prior history of CHF. Case subjects were defined as patients hospitalized for a first CHF and matched with up to 20 control subjects on age, duration of treated diabetes, calendar year, and time since cohort entry. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95% CIs of incident CHF comparing current use of incretin-based drugs with current use of two or more oral antidiabetic drugs. RESULTSThe cohort consisted of 57,737 patients followed for a mean 2.4 years, during which time 1,118 incident cases of hospitalized CHF were identified (incidence rate 8.1/1,000 person-years). Current use of incretin-based drugs was not associated with an increased risk of CHF (adjusted OR 0.85 [95% CI 0.62-1.16]). Secondary analyses revealed no duration-response relationship (P trend = 0.39). CONCLUSIONSIn our population-based study, incretin-based drug use was not associated with an increased risk of CHF among patients with type 2 diabetes. These findings provide some reassurance, but will need to be replicated in other large-scale studies.Incretin-based drugs, which consist of dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 analogs, were first approved by the U.S. Food and Drug Administration in 2006 for the treatment of type 2 diabetes. Both DPP-4 inhibitors and GLP-1 analogs improve glycemic control by increasing plasma levels of endogenous and exogenous GLP-1, respectively. This increase in GLP-1 stimulates insulin secretion and inhibits glucagon secretion (1).The cardiovascular safety of incretin-based drugs is currently under debate. This debate stems from a secondary analysis of the randomized controlled trial SAVOR-TIMI 53, in which saxagliptin was associated with an increased risk of congestive heart failure (CHF) (hazard ratio [HR] 1.27 [95% CI 1.07-1.51]) (2). In contrast, the EXAMINE trial found no association between alogliptin and CHF (HR 1.07 [95% CI 0.79-1.46]) (3). A subsequent meta-analysis of randomized controlled trials found an increased risk of CHF with DPP-4 inhibitors (relative risk 1.16 [95% CI 1.01-1.33]) (4), but these results were driven by those of SAVOR-TIMI 53. Although the safety

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Section: Sensitivity Analysesmentioning

confidence: 99%

Incretin-Based Drugs and the Risk of Congestive Heart Failure

Filion

Azoulay

et al. 2014

Diabetes Care

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“…One RCT investigated the effect of the blockbuster NSAID rofecoxib [64], which was later withdrawn from the international market due to an increased risk of cardiovascular events. Last, the safety of pioglitazone tested in the very large TOMMOROW trial has been questioned [35,65] and this antidiabetic drug is no longer marketed in some countries (e.g., France).…”

Section: Safety Concernsmentioning

confidence: 99%

Prevention Studies in Alzheimer’s Disease: Progress Towards the Development of New Therapeutics

2015

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Alzheimer's disease (AD) is the most common form of dementia and is a major cause of disability and dependency amongst older people. AD drugs approved so far are symptomatic treatments and are not thought to affect the underlying disease process. Trials conducted with agents aiming to slow or stop disease progression in patients with AD have all failed, perhaps because they were tested too late in the disease process. Therefore, there has been a move towards prevention of AD. This paper presents an overview of trials testing pharmacological interventions for sporadic AD prevention. Those tested to date were initially developed for the treatment of AD or for the treatment of other conditions, rather than being specifically developed for AD prevention. Associated issues, such as evidence of 'proof-of-concept,' doses and safety, are discussed. A major shift has taken place in the methodology of AD prevention trials since the results of the first trials were published in the 1990s. New directions that are currently being considered in ongoing or future prevention trials are discussed, in terms of endpoints, target populations, and study design. The use of AD-specific drugs to prevent AD in high-risk individuals is currently limited by a lack of validated predictive and surrogate markers. Population approaches, such as lifestyle changes, are an alternative strategy that could be of public health interest, but may provide only limited benefits for individuals. The best chance of preventing AD may come from a combination of individual and population prevention approaches. Key PointsFollowing the failure of treatment trials in symptomatic Alzheimer's disease (AD), there has been a move towards prevention of AD.To date, no specific pharmacological intervention has been developed for sporadic AD prevention and trial results have been disappointing.A major shift has taken place in the methodology of AD prevention trials and new directions are being considered in terms of endpoints, target populations, and study design.

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“…There are reports of increased bone fractures, congestive heart failure and bladder cancer with the use of Pioglitazone which have raised concerns about its long-term safety. [81][82][83] Elafibranor is a dual PPAR α/Y receptor agonist which has been evaluated in the treatment of NASH. After exclusion of mild cases, high dose elafibranor (120 mg/ day) was better than placebo in the resolution of NASH.…”

Section: (B) Peroxisome Proliferator-activated Receptors (Ppar) Agonistsmentioning

confidence: 99%

NAFLD therapy and monitoring disease progression

Puri¹,

Va²

2017

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The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study

Abstract: Objective To determine if the use of pioglitazone is associated with an increased risk of incident bladder cancer in people with type 2 diabetes.

Cited by 245 publications

References 35 publications

Incretin-Based Drugs and the Risk of Congestive Heart Failure

Incretin-Based Drugs and the Risk of Congestive Heart Failure

Prevention Studies in Alzheimer’s Disease: Progress Towards the Development of New Therapeutics

NAFLD therapy and monitoring disease progression

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