Original articleHypoglycaemic episodes in patients with type 2 diabetes – risk factors and associations with patient-reported outcomes: The PANORAMA Study
Introduction
Hypoglycaemia is a common side effect of some glucose lowering treatments and is associated with increased morbidity and mortality, as well as increased healthcare costs and lost productivity [1], [2], [3], [4], [5]. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) position statement on hyperglycaemia management in patients with type 2 diabetes recommends that in patients with a high risk of hypoglycaemia, advanced complications, and extensive comorbid conditions, initiation of treatments likely to induce hypoglycaemia should be delayed as long as possible. In addition, blood glucose targets may need to be moderated [6].
Episodes of hypoglycaemia can produce physical and psychological effects including sweating, palpitations, shaking, hunger, confusion, drowsiness, odd behaviour, speech difficulty, loss of coordination, and headaches [7]. The clinical consequences of hypoglycaemia can be serious, including seizures, loss of consciousness, injury [5], [7], cardiac ischemia [8], cardiac arrhythmias [9] and other cardiovascular events [10], [11], hospitalization, or death [12]. In the USA, adverse drug reactions to insulin and oral antidiabetes drugs (OADs) accounted for an estimated 22,726 emergency hospitalizations nationally per year between 2007 and 2009, in people aged ≥ 65 years, with 94.6% attributed to hypoglycaemia [3]. Overall, the second most common drug class associated with emergency hospitalizations was insulin (13.9%), and the fourth most common was OADs (10.7%) [3]. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, severe hypoglycaemia was associated with increased mortality in both standard and intensive treatment groups but mortality risk was not higher in the intensive than in the standard treatment group [1] and it has been suggested that hypoglycaemia, which was three times more frequent in the intensively treated group, could have been a contributory factor in some of the deaths [4], [10], [13], [14].
Even mild hypoglycaemia can be a psychological burden to patients, and fear of hypoglycaemia may inhibit adherence to treatment [15]. In the UK Prospective Diabetes Study (UKPDS), patients treated by insulin with ≥ 2 episodes of hypoglycaemia in the previous year had worse scores for psychological tension and overall mood disturbance, and reported lower work satisfaction than patients with no hypoglycaemia [16]. Nevertheless, there is a paucity of studies investigating associations between hypoglycaemia and patient-reported outcomes (PROs).
The PANORAMA study was designed to assess the quality of type 2 diabetes care in Europe with a large sample of patients with type 2 diabetes recruited in nine countries, managed mainly in primary care (NCT00916513). A previous analysis from PANORAMA evaluated glycaemic control in Europe [17]. This paper aims to assess the frequency and risk factors of severe and non-severe hypoglycaemic episodes and the PROs associated with them.
Section snippets
Study design
The PANORAMA study design has been detailed elsewhere [18]. Briefly, PANORAMA was an observational, cross-sectional study of people with type 2 diabetes, designed to be representative of the population of these patients in nine countries: Belgium, France, Germany, Greece, Italy, the Netherlands, Spain, Turkey, and the United Kingdom.
Study population
In each country, a random selection procedure was applied to databases of physicians managing patients with type 2 diabetes. Specialist or primary care physicians
Results
A total of 5817 patients were enrolled in PANORAMA. Four participants with data-reporting errors identified after database lock, were excluded from the current investigation. Fourteen patients had no data on episodes of severe hypoglycaemia, and 16 patients had taken both sulfonylureas and glinides in the previous year, giving a sample size of 5783 patients. Of the data reported in univariate analyses, 81.5% of variables had < 5% missing data.
During the previous year, 254/5783 (4.4%) patients
Discussion
The PANORAMA study found that a bit more than 20% of patients with type 2 diabetes reported hypoglycaemic events (including 4.4% severe hypoglycaemia) during the past year. Hypoglycaemic episodes mostly occurred in patients treated by insulin (among this group, 14.2% experienced severe and 39.3% non-severe hypoglycaemia) and insulin secretagogues (glinides [5.4% and 22.1%] and sulfonylureas [2.6% and 14.4%]). In comparison, rates of severe hypoglycaemia for patients with type 1 diabetes in the
Disclosure of interest
The PANORAMA study was sponsored by AstraZeneca and Bristol-Myers Squibb, who were involved in: the design and conduct of the study; data collection, analysis and interpretation; preparation and review of the manuscript, and decision to submit the manuscript for publication. C.B., D.S., and P.d.P. are co-chairs of the PANORAMA steering committee. All non-company authors have received honoraria/consulting fees for their participation on the PANORAMA Study Advisory Committee. All non-company
Acknowledgements
The authors would like to thank Monica Tafalla, PhD, an employee of AstraZeneca at the time of the study, for overall management of the trial and Pierre Maheux, MD, an employee of AstraZeneca at the time of the study, who contributed to the study design, interpreted the study data, and critically reviewed the manuscript.
Sally Cotterill, PhD, and Nikki Kendrick, BSc, (QXV Communications, Macclesfield, UK) and Carole Nadin, MPhil, (technical writer) provided assistance in the manuscript
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