Pioglitazone (Actos) Reduced Risk of Secondary Stroke and New Onset of Diabetes

MedicalResearch.com Interview with:

David Spence M.D., FRCPC, FAHA Professor of Neurology and Clinical Pharmacology Director, Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University London, ON Canada

Dr. Spence

David Spence M.D., FRCPC, FAHA
Professor of Neurology and Clinical Pharmacology
Director, Stroke Prevention & Atherosclerosis Research Centre,
Robarts Research Institute, Western University
London, ON Canada

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The motivation for the study was the chair of the committee that advises the Ontario Drug Benefit which medications to pay for said the IRIS results were not relevant to clinical practice. This because the Insulin Resistance Intervention after Stroke (IRIS) trial reported effects of pioglitazone in patients with stroke or TIA and insulin resistance assessed by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score for insulin resistance.1 ( However, few clinicians measure a HOMA-iR score, so the clinical impact of that trial was limited.

In this study we analyzed the effect of pioglitazone in stroke/TIA patients with prediabetes, which is commonly assessed by clinicians. Prediabetes was defined by the American Diabetes Association: a glycosylated hemoglobin (A1C) of  5.7% to <6.5% (we did not do glucose tolerance tests).  We analyzed primarily the results for patients with 80% adherence, but also did  an intention-to-treat (ITT) analysis.  The reason for focusing on patients with good adherence was that pioglitazone cannot be taken by about 10-20% of patients, because of fluid retention and weight gain (mainly due  to fluid retention).  (The reasoning was that third party payers would not need to pay for the medication in patients who do not take it.)

In stroke/TIA patients with good adherence, the benefits of pioglitazone were greater than in the original IRIS trial. We found a 40% reduction of stroke/MI, a 33% reduction of stroke, and an 80% reduction of new-onset diabetes, over 5 years.  Pioglitazone also improved blood pressure, triglycerides and HDL-cholesterol. As expected, pioglitazone was somewhat less beneficial in the ITT analysis.

Fluid retention can usually be managed by reducing the dose of pioglitazone; even small doses still have a beneficial effect . Also, amiloride has been shown to reduce fluid retention with pioglitazone.

  1. Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP, Jr., Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O’Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR and Investigators IT. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016;374:1321-31. 

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Link Between Number of Migraines and Diabetes Risk

MedicalResearch.com Interview with:

Guy Fagherazzi, MSc, PhD, HDR Senior Research Scientist in Digital & Diabetes Epidemiology Center of Research in Epidemiology and Population Health  Inserm, Paris-South Paris-Saclay University

Dr. Guy Fagherazzi

Guy Fagherazzi, MSc, PhD, HDR
Senior Research Scientist in Digital & Diabetes Epidemiology
Center of Research in Epidemiology and Population Health
Inserm, Paris-South Paris-Saclay University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Migraine has further been associated with increased risk of overall and specific cardiovascular disease events.

Because migraine has also been associated with factors related with insulin resistance and type 2 diabetes, an association between migraine and diabetes has been hypothesized.

We observed a lower risk of type 2 diabetes in women with active migraine.

We also show a linear decrease of migraine prevalence long before and a plateau long after type 2 diabetes diagnosis. 

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Current Web-Based Risk Tool May Overestimate Risk of Pre-Diabetes

MedicalResearch.com Interview with:

Dr. Saeid Shahraz Assistant Professor of Medicine Tufts Medical Center

Dr. Saeid Shahraz

Dr. Saeid Shahraz
Assistant Professor of Medicine
Tufts Medical Center

MedicalResearch.com: What is the background for this study?
Response: American Diabetes Association (ADA) has set up a lower cut point for diagnosing prediabetes ( those with Impaired Fasting  Glucose   100 mg/dL) compared to the World Health Organization’s cut point, which is 110 mg/dL. This arbitrariness in cut point definition triples the number of cases labeled as prediabetes.

Along with lowering the diagnostic threshold by the ADA, the Centers for Disease Control and Prevention (CDC), the American Medical Association (AMA), and the ADA endorsed and advertised a web-based risk model to define high-risk population for prediabetes. The risk engine asks a few questions ( age, sex, family history of diabetes, history of gestational diabetes and high blood pressure, physical activity and weight) and outputs a score that defines if the person is at risk for prediabetes. We suspected that the risk engine might overestimate the risk.

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Pre-Diabetes Associated With Increased All-Cause and Cardiovascular Mortality

MedicalResearch.com Interview with:
Yuli Huang and Yunzhao Hu
Department of Cardiology, the First People’s Hospital of Shunde,
Shunde District, Foshan, PR China.

Medical Research: What are the main findings of the study?

Response: “Prediabetes” is a general term that refers to an intermediate stage between normoglycaemia and overt type 2 diabetes mellitus (T2DM). It includes 2 groups of individuals, those with impaired glucose tolerance (IGT) and those with impaired fasting glucose (IFG). In 2003, the American Diabetes Association (ADA) redefined the fasting plasma glucose (FPG) concentration range for diagnosing IFG from 110 to 125 mg/dl to 100 to 125 mg/dl in order to better identify individuals at future type 2 diabetes mellitus risk. However, this change has been contentious and was not adopted by the World Health Organization (WHO) Expert Group or other international guidelines.

In this meta-analysis, we included data from 26 prospective cohort studies with for 280,185 participants and found that, after controlling for multiple cardiovascular risk factors, the presence of prediabetes at baseline, defined as defined as IFG of 110 to 125 mg/dL(IFG 110), IGT or combined IFG 110 and/or IGT, was associated with increased risk of all-cause and cardiovascular mortality. Specifically, IFG 110 was associated with 12% and 19% increase of all-cause and cardiovascular mortality, IGT was associated with 33% and 23% increase of all-cause and cardiovascular mortality, combination of IFG110 and/or IGT was associated with 21% and 21% increase of all-cause and cardiovascular mortality, respectively. Although IFG 100 was not associated with all-cause or cardiovascular mortality in the overall analysis, the risk was greater in young and middle age males according to subgroup analyses.

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Prediabetes Associated With Increased Cancer Risk

Professor Yuli Huang The First People's Hospital of Shunde, Daliang Town, China, and colleaguesMedicalResearch.com Interview with:
Professor Yuli Huang
The First People’s Hospital of Shunde, Daliang Town, China, and colleagues


Medical Research: What are the main findings of the study?

Professor Huang: In this meta-analysis of 16 prospective cohort studies comprising more than 890,000 individuals, we found that the presence of prediabetes at baseline associated with a 15% increased risk of cancer overall. The results were consistent across cancer endpoint, age, duration of follow-up and ethnicity. There was no significant difference for the risk of cancer with different definitions of prediabetes (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]).
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