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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Endocrine Disorders 1/2015

Drug-related risk of severe hypoglycaemia in observational studies: a systematic review and meta-analysis

BMC Endocrine Disorders > Ausgabe 1/2015
Marcin Czech, Elżbieta Rdzanek, Justyna Pawęska, Olga Adamowicz-Sidor, Maciej Niewada, Michał Jakubczyk
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12902-015-0052-z) contains supplementary material, which is available to authorized users.

Competing interests

The project was supported by an unrestricted scientific grant from Novo Nordisk. The author(s) declare that they have no competing interests. There is no specific organization that may in any way gain or lose financially from the publication of this manuscript.

Authors’ contributions

MJ, JP, MN, ER, and MC are the authors of the general approach. MJ, JP, ER, OAS, and MN participated in the systematic review. MJ designed the statistical approach. All authors participated in preparing, reading, and approving the final manuscript.



Diabetes mellitus (DM) leads to multiple complications, including severe hypoglycaemia events (SHEs). SHEs can impact a patient’s quality of life and compliance and may directly result in additional costs to the health care system. The aim of this review was to evaluate the risk of severe hypoglycaemia in patients with type 1 (T1) and 2 (T2) DM as observed in everyday clinical practice for various drug regimens.


We conducted a systematic review of observational (retrospective or prospective) studies in the MEDLINE, Embase, and Cochrane Library databases that covered at least 100 children or adults with T1/T2 DM. In T1 DM, basal-bolus/pre-mix insulin (human or analogue) and insulin pump were reviewed, and in T2 DM, basal-bolus/pre-mix insulin (human or analogue), oral antidiabetic drugs supported with basal insulin (human or analogue), sulfonylureas in monotherapy, and combined oral treatment were reviewed. In order to estimate SHE rates, we extracted data on the time horizon of the study, number of patients, number of SHEs, and number of patients experiencing at least one SHE. We used a random effects model to estimate the annual SHE rate. We considered the risk for other antidiabetic medications in T2 DM to be negligible and the results of our main review yielded no observational data for premixes in T1 DM so they were assessed based on relative rates taken from additional systematic reviews. The study, being a desk research, did not involve any human subjects (including human material or human data) and no ethical committee approval was asked for. For the same reason there was no need to collect informed consent for participation in the study.


We identified 76 observational studies encompassing 707,722.30 patient-years. The estimated annual SHE rate varied from 0.168 (95 % CI 0.123–0.237) for insulin pump up to 1.628 for biphasic human insulin in T1 DM patients, and from 0.0035 for oral antidiabetic drugs up to 0.554 (95 % CI 0.157–7.534) for basal-bolus with human insulin in T2 DM patients.


Our review indicates that SHE rates differ between patients depending on treatment regimen. However, SHEs are also driven by other factors. Proper modelling techniques are needed to use various types of information in published studies.
Additional file 1: Search strategies. (PDF 220 kb)
Additional file 2: Model specification and JAGS codes. (PDF 343 kb)
Additional file 3: Study selection process. (PDF 318 kb)
Additional file 4: Studies characteristics. (PDF 332 kb)
Additional file 5: Individual studies data. (PDF 466 kb)
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