Hypoglycemia Event Rates: A Comparison Between Real-World Data and Randomized Controlled Trial Populations in Insulin-Treated Diabetes

Diabetes Ther. 2016 Mar;7(1):45-60. doi: 10.1007/s13300-016-0157-z. Epub 2016 Feb 17.


Introduction: Hypoglycemia is the most common adverse effect of diabetes therapy, particularly insulin treatment. Hypoglycemia is associated with considerable clinical and economic burden, and may be under-reported. The aim of this study was to com pare the frequency of hypoglycemic events reported in real-world settings with those reported in clinical trials.

Methods: We conducted a structured literature review in PubMed to identify hypoglycemic event rates in patients with type 1 diabetes mellitus (T1DM) and insulin-treated type 2 diabetes mellitus (T2DM) from real-world data (RWD) and randomized controlled trials (RCTs). The search was restricted to English language, full-text publications from 2010 onwards, reporting on treatment of T1DM or T2DM with basal only, basal-bolus, or premix insulin.

Results: The final dataset included 30 studies (11 RWD studies and 19 RCTs). Six studies (RWD, n = 2; RCT, n = 4) reported hypoglycemia event rates in people with T1DM. For all reported categories of hypoglycemia (severe, non-severe, and nocturnal), rates were consistently higher in RWD studies compared with RCTs. Twenty-five studies (RWD, n = 10; RCT, n = 15) reported hypoglycemia event rates in people with insulin-treated T2DM. For T2DM basal-oral therapy; the highest rates were observed in RWD studies, although there was an overlap with RCT rates. For basal-bolus therapy, there was considerable between-study variability but higher rates of severe and non-severe hypoglycemia were generally observed in RWD studies. For T2DM premix insulin, reported rates of hypoglycemia in RWD studies and RCTs were similar.

Conclusion: We found that higher rates of hypoglycemia are observed in real-world settings compared with clinical trial settings, although there is a large degree of overlap. Due to the inherent constraints of RCTs, they are likely to underestimate the burden of hypoglycemia in clinical practice. Further, high-quality RWD are needed to determine a more accurate incidence of hypoglycemia in clinical practice.

Keywords: Clinical trial data; Diabetes mellitus; Hypoglycemia; Hypoglycemia event rates; Insulin; Nocturnal hypoglycemia; Real world data; Severe hypoglycemia.