Severe hypoglycemia in patients with diabetes is an adverse drug event that is associated with poor outcomes, such as cardiovascular events, falls, high rehospitalization rates, and increased mortality (1,2). Several strategies, including adjustment of glucose-lowering therapy and glycemic targets, have been recommended in patients with severe hypoglycemia (1,3). However, it is not clear how changes in diabetes management are maintained after severe hypoglycemia among patients with type 2 diabetes.
We conducted a retrospective analysis of data from the OptumLabs Data Warehouse, a de-identified administrative claims database of over 200 million individuals enrolled in commercial and Medicare Advantage plans across the U.S. (4). Data were accessed in adherence with the Health Insurance Portability and Accountability Act of 1996, and the Yale School of Medicine Human Investigations Committee deemed the study exempt from institutional review board review.
We included commercially insured or Medicare Advantage beneficiaries who were aged 18 years or older, had pharmacologically treated type 2 diabetes, and had a severe hypoglycemic event. Severe hypoglycemia was identified as the first event during an observation window of 1 July 2013 through 30 June 2014, based on primary/principal diagnosis codes for hypoglycemia from an emergency department visit, observation stay, or hospital admission. We assessed changes in diabetes management by examining prescription fills for glucose-lowering medications, glucagon, and test strips; HbA1c levels (on a subsample of patients); and outpatient care 6 months before and 6 months after the hypoglycemia-related health care utilization. We used paired two-sample t tests for continuous variables and McNemar test statistic for paired categorical variables in R software.
Among 5,721 patients with type 2 diabetes with severe hypoglycemia, median age was 69 years (interquartile range [IQR] 60–77), 51% were women, 63% were White, 20% were Black, 68% used insulin, and 37% used sulfonylureas. Of the 1,305 patients with available HbA1c values, median baseline HbA1c was 7.5% (range 4.3–17.6%). Changes in diabetes management are summarized in Table 1. The proportion of patients seeing an endocrinologist for diabetes management rose slightly from 16.7% to 18.2% but remained low. Only 30.5% of patients with a baseline HbA1c <6% had an absolute increase in HbA1c of at least 0.5% after hypoglycemia. Of the 905 patients filling prescriptions for both insulin and a sulfonylurea prior to severe hypoglycemia, 638 (70.5%) continued to fill both drug classes after the event. Glucagon was filled by fewer than 5% of patients.
Table 1.
Changes in diabetes management before and after hypoglycemia-related encounter
| 6 months before | 6 months after | P value | |
|---|---|---|---|
| Office visits | |||
| Number of office visits with any clinician | 6 (3–9) | 7 (4–11) | <0.001 |
| Patients seeing an endocrinologist, N (%) | 956 (16.7) | 1,044 (18.2) | <0.001 |
| Time to office visit after hypoglycemia (days) | — | 12 (6–27) | |
| Diabetes self-management | |||
| Patients with glucagon fills, N (%) | 203 (3.55) | 143 (2.50) | <0.001 |
| Number of test strips filled per month | 50 (16.7–91.7) | 50 (33.3–108.3) | <0.001 |
| Patients using continuous glucose monitoring, N (%) | 96 (1.68) | 53 (0.93) | <0.001 |
| Glycemic control (n = 1,305) | |||
| HbA1c (%) | 7.5 (6.6–8.9) | 7.4 (6.5–8.7) | <0.001 |
| Increase in HbA1c by 0.5% or more (by baseline HbA1c), N (%) | <0.001 | ||
| <6% (n = 141) | — | 43 (30.5) | |
| 6–7% (n = 327) | — | 93 (28.4) | |
| 7–8% (n = 292) | — | 62 (21.2) | |
| 8–9% (n = 229) | — | 40 (17.5) | |
| ≥9% (n = 316) | — | 31 (9.8) | |
| Patients with diabetes medication fills, N (%) | |||
| Any insulin | 3,864 (67.5) | 3,967 (69.3) | <0.001 |
| Human insulin | 654 (11.4) | 645 (11.3) | 0.443 |
| Analog insulin | 3,494 (61.1) | 3,661 (64.0) | <0.001 |
| Basal insulin | 2,895 (50.6) | 3,111 (54.4) | <0.001 |
| Bolus insulin | 2,371 (41.4) | 2,609 (45.6) | <0.001 |
| Premixed insulin | 786 (13.7) | 727 (12.7) | 0.010 |
| Sulfonylureas | 2,117 (37.0) | 1,754 (30.7) | <0.001 |
| Glinides | 105 (1.8) | 112 (2.0) | 0.341 |
| Biguanides | 2,528 (44.2) | 2,246 (39.3) | <0.001 |
| TZDs | 339 (5.9) | 261 (4.6) | <0.001 |
| DPP-4 inhibitors | 819 (14.3) | 784 (13.7) | 0.055 |
| GLP-1 agonists | 260 (4.5) | 218 (3.8) | <0.001 |
| Other medications | 213 (3.7) | 211 (3.7) | 0.904 |
Data are median (IQR) unless otherwise specified. DPP-4, dipeptidyl peptidase 4; GLP-1, glucagon-like peptide 1; TZDs, thiazolidinediones.
In this national study of commercially insured and Medicare Advantage patients with type 2 diabetes who experienced a severe hypoglycemic event, the use of sulfonylureas declined, but few other changes in diabetes management were evident following the event. These findings suggest there are significant opportunities to prevent recurrent hypoglycemia in the future.
Multiple prior studies have demonstrated glycemic overtreatment among older patients at risk for hypoglycemia (5) and low rates of treatment deintensification. Our findings suggest that even after a severe hypoglycemic event, changes in management are infrequently made. Clinicians may have few options other than insulin in patients with long-standing diabetes and multiple comorbidities, and our study could not capture dose reductions in insulin that may have occurred. Still, most individuals with a low baseline HbA1c did not have an increase in HbA1c level after hypoglycemia, so any dose reductions were not reflected in the measured levels of glycemia. In addition, the low level of glucagon use suggests a missed opportunity to mitigate the risks of insulin use.
Our study has other limitations. It is an observational study, and as such we cannot make inferences about the appropriateness of individual clinical decisions reflected in these data. It is possible that more recent data may demonstrate improvements in implementation of these recommendations. In addition, we did not include patients with severe hypoglycemia treated in the community; thus, our study includes a small subset of patients with type 2 diabetes exposed to severe hypoglycemia. Finally, we measured prescription fills and HbA1c levels, both of which may be affected by patient adherence to clinician recommendations or cost of medications and devices.
There are many barriers to timely treatment deintensification. Clinicians may be constrained by performance metrics and population health management efforts that reward lowering HbA1c levels without balancing minimization of hypoglycemic events. These barriers may be addressed by development and integration of quality metrics focused on hypoglycemia. The overall lack of change in management highlighted by this study may also be due to inadequate integration of care, insufficient awareness of guideline recommendations, or lack of specificity in clinical recommendations on how to effectively prevent recurrent hypoglycemia-related utilization.
Article Information
Funding. This project was supported by the National Institute on Aging and the American Federation of Aging Research through the Paul B. Beeson Emerging Leaders Career Development Award in Aging to K.J.L. (K23AG048359), as well as National Institute on Aging grant R01 AG063391 and National Institute of Diabetes and Digestive and Kidney Diseases grant R01 DK103721 to A.J.K.
Duality of Interest. A.J.K. received research support from Dexcom outside of this study. K.J.L. receives support from the Centers for Medicare & Medicaid Services to develop publicly reported quality measures. No other potential conflicts of interest relevant to this article were reported.
Author Contributions. P.V. and K.J.L. conceived of and designed the study. K.J.L. obtained funding and acquired the data. P.V., S.L., and K.J.L. analyzed and interpreted the data. S.L. performed statistical analysis. P.V. drafted the manuscript. S.L., R.G.M., and A.J.K. critically revised the manuscript for important intellectual content. K.J.L. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Prior Presentation. Parts of this work were presented in abstract form at the 79th Scientific Sessions of the American Diabetes Association, 7–11 June 2019.
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