Rosiglitazone and Pioglitazone Utilization from January 2007 Through May 2008 Associated With Five Risk-Warning Events

Starner, Catherine I.; Schafer, Jeremy A.; Heaton, Alan; Gleason, Patrick P.

doi:10.18553/jmcp.2008.14.6.523

Cited by 85 publications

(60 citation statements)

References 11 publications

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“…Although the subgroup of patients with no additions to glucose-lowering therapies had greater and more stable weight loss, we were unable to explore the influence of discontinuing concomitant therapies; in particular, some weight loss may have occurred in patients who discontinued thiazolidinediones or sulfonylureas. Changes in practice may have affected the trial; due to new clinical perspectives regarding cardiovascular profiles of T2D treatments, routine use of thiazolidinediones decreased during the course of the trial, 17 potentially contributing, at least partially, to the gradual mean weight loss after year 3. Data were not collected on patient dieting or other lifestyle changes that could have influenced body weight findings.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study

Henry

Klein²,

Han

et al. 2016

Diabetes Technology & Therapeutics

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Background: Long-term treatment is necessary to slow the progression of type 2 diabetes (T2D). Here, we examined the safety and efficacy of 6 years of treatment with exenatide once weekly (QW) among patients with T2D in the DURATION-1 trial.Methods: The study enrolled patients aged ≥16 years with T2D treated primarily with metformin and sulfonylureas. Following 30 weeks of randomized treatment with exenatide QW 2 mg or exenatide twice daily 10 μg, patients entered an uncontrolled, open-label, open-ended study phase in which all patients received exenatide QW 2 mg. Restrictions on concomitant medication use were eased over time.Results: Of the original 295 patients in the intent-to-treat population, 136 (46%) completed 6 years of treatment. Six-year completers had sustained significant improvements from baseline in glycated hemoglobin (HbA1c; least-squares mean [LSM] change, −1.6%), with 46.3% achieving HbA1c <7.0%, 33.1% achieving HbA1c ≤6.5%, and significant improvements from baseline in fasting plasma glucose (−28 mg/dL) and body weight (−4.2 kg) at 6 years. The 78 completers who added no glucose-lowering medications had numerically greater body weight reductions than the overall cohort (6-year LSM change, −6.1 kg) with more stability over time. No unexpected adverse events were observed during 1202.4 patient-years of exposure. Most minor hypoglycemia events occurred with concomitant sulfonylurea use.Conclusions: Exenatide QW was associated with clinically significant, sustained improvements in glycemic control and weight in patients who continued therapy for up to 6 years, without unexpected safety findings. registration: NCT00308139.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study

Henry

Klein²,

Han

et al. 2016

Diabetes Technology & Therapeutics

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“…These agents, through PPARγ, can also stimulate adipocyte differentiation [3–6]. One potential side effect of administration of TZDs is edema (reviewed in [7]), suggesting possible effects of these agents on fluid balance; however, reports concerning pioglitazone effects on aldosterone levels in vivo are controversial. Thus, some investigators have reported no effect of TZDs on serum aldosterone levels [8,9], whereas others have reported that these drugs decrease serum aldosterone levels [10].…”

Section: Introductionmentioning

confidence: 99%

The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells

Pan

Xie

Choudhary

et al. 2014

Molecular and Cellular Endocrinology

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Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24hr significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention.

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“…6,7 As a result of these warnings, large declines in rosiglitazone prescriptions were observed in clinical practice in the United States. 3,8–15 …”

mentioning

confidence: 99%

Geographic Variation in Rosiglitazone Use Surrounding FDA Warnings in the Department of Veterans Affairs

Ahuja

Sohn²,

Birge³

et al. 2015

JMCP

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BACKGROUND Geographic variation in the use of prescription drugs, particularly those deemed harmful by the FDA, may lead to variation in patient exposure to adverse drug events. One such drug is the glucose-lowering drug rosiglitazone, for which the FDA issued a safety alert on May 21, 2007, following the publication of a meta-analysis that suggested a 43% increase in the risk of myocardial infarction with the use of rosiglitazone. This alert was followed by a black box warning on August 14, 2007, that was updated 3 months later. While large declines have been documented in rosiglitazone use in clinical practice, little is known about how the use of rosiglitazone and other glucose-lowering drugs varied within the Department of Veterans Affairs (VA), surrounding the FDA alerts. Understanding this variation within integrated health care systems is essential to formulating policies that enhance patient protection and quality of care. OBJECTIVE To document variation in the use of rosiglitazone and other glucose-lowering drugs across 21 Veterans Integrated Service Networks (VISNs). METHODS We conducted a retrospective analysis of drug use patterns for all major diabetes drugs in a national cohort of 550,550 veterans with diabetes from 2003 to 2008. This included the time periods when rosiglitazone was added to (November 2003) and removed from (October 2007) the VA national formulary (VANF). We employed multivariable logistic regression models to statistically estimate the association between a patient’s location and the patient’s odds of using rosiglitazone. RESULTS Aggregate rosiglitazone use increased monotonically from 7.7%, in the quarter it was added to the VANF (November 4, 2003), to a peak of 15.3% in the quarter when the FDA issued the safety alert. Rosiglitazone use decreased sharply afterwards, reaching 3.4% by the end of the study period (September 30, 2008). The use of pioglitazone, another glucose-lowering drug in the same class as rosiglitazone, was low when the FDA issued the safety alert (0.4%) but increased sharply afterwards, reaching 3.6% by the end of the study period. Insulin use increased monotonically; metformin use remained relatively flat; and sulfonylurea use exhibited a general declining trend throughout the study period. Statistically significant geographic variation was observed in rosiglitazone use throughout the study period. The prevalence range, defined as the range of minimum to maximum use across VISNs was 3.7%–12.4% in the first quarter (January 1 to March 31, 2003); 1.0%–5.5% in the last quarter of study period (July 1 to September 30, 2008); and reached a peak of 9.6%–25.5% in the quarter when the FDA safety alert was issued (April 1 to March 31, 2007). In 5 VISNs, peak rosiglitazone use occurred before the FDA issued the safety alert. The odds ratio of using rosiglitazone in a given VISN varied from 0.55 (95% CI = 0.52–0.59; VISN 10) to 1.58 (95% CI = 1.50–1.66; VISN 15), with VISN 1 being the reference region. The variation was higher in the periods after the FDA issued ...

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Rosiglitazone and Pioglitazone Utilization from January 2007 Through May 2008 Associated With Five Risk-Warning Events

Cited by 85 publications

References 11 publications

Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study

Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study

The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells

Geographic Variation in Rosiglitazone Use Surrounding FDA Warnings in the Department of Veterans Affairs

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