Are there any sex specific differences in the general efficacy and safety of oral antidiabetic therapies (versus placebo, observation, no intervention) to avoid manifestation of diabetes in a population with prediabetes?

Are there any sex specific differences in the general efficacy and safety of lifestyle interventions (observation, no intervention) to avoid a manifestation of diabetes in a population with prediabetes?

Are there any sex specific differences in the relative efficacy and safety of oral antidiabetic therapies versus lifestyle-interventions to avoid a manifestation of diabetes in a population with prediabetes?

Various electronic databases: PubMed, EMBASE, Cochrane Library

Grey literature (grey matters, open grey)

Unpublished data from manufacturers, if available

Search date: 1980-2012

Languages: English, German

Manual search: semi-automated with Scopus

Dual review of the literature

To assess the comparative benefit, randomised controlled studies (RCTs) or systematic reviews and meta-analyses of RCTs will be taken into account. The minimum study duration is one year.

To assess side effects, additionally controlled, prospective cohort studies with low or unclear bias risk will be included (minimum study size n=500, study duration minimum 1 year).

The aim of this project is to systematically evaluate the gender-related comparative effectiveness and safety of pharmacotherapy versus lifestyle modification in prevention of diabetes manifestation in prediabetics.

Impaired fasting glucose (IFG) as well as impaired glucose tolerance (IGT), isolated or combined, are precursors of a diabetic metabolic status and often persist years before diagnosis of type II diabetes. Gender-specific and age-related differences in IFG and IGT frequency have been observed, which may delay diabetes diagnosis and individual risk factor detection. Diabetes preventive actions have been studied in depth, but gender-specific differences in efficacy were rarely taken into account. To fill this knowledge gap the current review focuses on the gender-specific differences.

People with prediabetes/pre-diabetic state aged between 25 and 70 years:

• Impaired fasting glucose (IFG): elevated fasting blood glucose level from 5.6 mmol/L (100 mg/dL) to 6.9 mmol/L (125 mg/dL)

AND/OR

• Impaired glucose tolerance (IGT): two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test. A patient is said to be under the condition of IGT when he/she has an intermediately raised glucose level after 2 hours, but less than would qualify for type 2 diabetes mellitus.

Women with gestational diabetes are excluded for lack of a corellating male control group.

1. Drugs (Pharmacolgical classification)

Metformin (Biguanide)

Acarbose (Alpha (a)-glucosidase inhibitor)

Voglibose (Alpha (a)-glucosidase inhibitor)

Pioglitazone (Insulin-sensitizer)

Rosiglitazone (Insulin-sensitizer)

Troglitazone (Insulin-sensitizer)

Liraglutide (GLP1 (Glucagon-like peptide-1) Analogue)

Exenatide (GLP1 Analogue)

Nateglinide (Glinide)

Repaglinide (Glinide)

Sitagliptin (DPP4 (dipeptidyl peptidase-IV) - Inhibitor)

Vildagliptin (DPP4 Inhibitor)

Linagliptin (DPP4 Inhibitor)

Saxagliptin (DPP4 Inhibitor)

Insulin Glargine

2. Lifestyle-Modification: diet, physical activity

Placebo or active control, no dose range studies.

Primary outcomes

Sex-specific differences in the Incidence of Diabetes Mellitus manifestation (fasting blood glucose level > 126 mg/dl, oral glucose tolerance test: 2 hours postprandial glucose level > 200 mg/dl)

Secondary outcomes

Sex-specific differences of health related quality of life

Sex-specific differences in adverse events

Sex-specific differences in morbidity and mortality

We will use standardized data extraction forms into which trained reviewers abstract data from each study and assign an initial rating of the risk of bias. A senior reviewer will evaluate the forms.

All eligible studies will be dually reviewed based on the Cochrane Risk of Bias Tool.

To assess the risk of bias of observational studies, we employ criteria outlined by Deeks et al., for systematic reviews we use the AMSTAR (Assessment of Multiple Systematic Reviews) tool.

The strength of evidence for the most important outcomes will be assessed according to GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool.

A descriptive analysis of all selected studies, which address our predefined key question will be provided. When data on a particular outcome of interest are sufficient, we plan to conduct a meta-analysis of the odds ratio of experiencing an event.

Subgroup-Analysis for all key questions:

Patients with metabolic syndrome according to the WHO-definition:

• Hypertension: if blood pressure = 140/90 mmHg

• Dyslipidaemia: tryglicerides > 1.695 mmol/l, HDL = men 0.9 mmol/l, women = 1.0 mmol/l

• Visceral adipositas: waist-hip ratio for men > 0.9, for women > 0.85 and/or a BMI > 30 kg/m2

Sonja Rohleder

Danube University Krems

Department for Evidence-based Medicine and Clinical Epidemiology

Dr.-Karl-Dorrek-Straße 30

3500 Krems an der Donau

Austria

sonja.rohleder@meduniwien.ac.at

Medical University of Vienna & Danube University Krems

www.meduniwien.ac.at and http://www.donau-uni.ac.at

Dr Anna Glechner, Danube University Krems
Dr Juergen Harreiter, Medical University of Vienna
Dr Sonja Rohleder, Danube University Krems & Medical University of Vienna
Mr Alexander Kautzky, Medical University of Vienna
Mrs Megan Grace Van Noord, Danube University Krems
Dr Angela Kaminski - Hartenthaler, Danube University Krems
Professor Gerald Gartlehner, Danube University Krems
Professor Jaako Tuomilehto, Danube University Krems & University of Helsinki
Professor Alexandra Kautzky - Willer, Medical University of Vienna

18 September 2012

18 September 2013

Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien (Medical-Scientific Foundation of the Major of the Federal Capital Vienna)

None known

English

Austria

Subject indexing assigned by CRD

Diabetes Mellitus; Health Promotion; Humans; Hypoglycemic Agents; Life Style; Primary Prevention; Sex Factors

16 October 2012

30 October 2012