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

Abstract

BackgroundDiabetes 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-015-0052-z) contains supplementary material, which is available to authorized users.

Temporal changes in the incidence and predictors of severe hypoglycaemia in type 2 diabetes: The Fremantle Diabetes Study

“…The crude incidence of severe hypoglycaemia in the FDS2 (1.34/100 participant‐years) was not significantly different from that in the FDS1 (1.67/100 participant‐years) and, as reported previously after allowing for differences in populations and ascertainment of events, consistent with the overall incidence in type 2 diabetes found in other epidemiological studies . When much higher rates have been reported, this has been when severe episodes have been ascertained in only insulin‐treated patients (who also had relatively high rates in the present study, especially those on pre‐mixed or basal‐bolus regimens) and/or from those requiring second‐party assistance rather than the much more restrictive criteria used in the present study.…”

Efficacy and safety of teneligliptin in Indian patients with inadequately controlled Type 2 diabetes mellitus: A randomized, double-blind study

“…[ 19 ] Similarly, a recently conducted meta-analysis reported that patients who receive basal bolus insulin have a 33.7% risk of a severe hypoglycemic events, while patients treated with sulphonylurea have a 3.5% annual risk of a severe hypoglycemic event. [ 20 ] The use of teneligliptin in this study was not associated with any significant changes in laboratory findings (SGPT, ALP, SGOT, serum amylase, and serum calcitonin).…”

Reversal of Early Diabetic Nephropathy by Islet Transplantation under the Kidney Capsule in a Rat Model

“…However, because islet transplantation is capable of physiologic regulation in vivo , it can control the secretion of insulin automatically to maintain the blood glucose level within the normal range. Hypoglycemia is considered one of the most dangerous complications occurring in clinically diabetic patients, and intensive insulin therapy protocols have been widely used in the clinical intensive care of diabetes mellitus; notably, the incidence of hypoglycemia is markedly increased if the blood glucose level is not constantly monitored [ 33 ]. Nevertheless, because of the self-regulation of physiological systems, excessive insulin secretion does not occur after islet transplantation.…”