Effect of Continuous Glucose Monitoring on Hypoglycemia in Older Adults With Type 1 Diabetes: A Randomized Clinical Trial

Abstract

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes.

Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes.

Design, setting, and participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes.

Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100).

Main outcomes and measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate.

Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8).

Conclusions and relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit.

Trial registration: ClinicalTrials.gov Identifier: NCT03240432.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Pratley reported lecture and/or consultancy fees and/or grants paid to his institution, AdventHealth, from AstraZeneca, Boehringer Ingelheim, Eisai Inc, GlaxoSmithKline, Glytec LLC, Janssen, Lexicon Pharmaceuticals, Ligand Pharmaceuticals Inc, Lilly, Merck, Mundipharma, Novo Nordisk, Pfizer, Sanofi, and Takeda; receipt of grants from Lexicon Pharmaceuticals, Ligand Pharmaceuticals Inc, Lilly, Merck, Novo Nordisk, Sanofi, and Takeda; and receipt of personal fees from Sanofi US Services Inc. Dr Rickels reported receipt of personal fees from Hua Medicine, Xeris Pharmaceuticals, Semma Therapeutics, and Sernova; grants from Xeris Pharmaceuticals; and nonfinancial support from Merck & Co. Dr Ahmann reported contract research payments to his institution from Dexcom and receipt of personal fees from Medtronic. Dr Aleppo reported receipt of grants from Novo Nordisk, Dexcom, AstraZeneca, and Lilly and personal fees from Dexcom, Medtronic, Insulet, and Novo Nordisk. Dr Beck reported consulting fees paint to his institution from Bigfoot Biomedical, Tandem Diabetes Care, Insulet, and Lilly and receipt of grants from Dexcom and Tandem Diabetes Care and nonfinancial support from Dexcom, Tandem Diabetes Care, Roche, and Ascensia. Dr Bhargava reported receipt of grants from Sanofi, AstraZeneca, Lilly, United BioSource Corporation, Dexcom, Teijin America Inc, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Bristol-Meyers Squibb Research and Development, Gan & Lee Pharmaceutical, the Jaeb Center for Health Research, KOWA Research Institute Inc, Medtronic MiniMed, Mylan GmbH, Novo Nordisk, AstraZeneca, Lilly, and Theracos Sub LLC; speaker fees from Sanofi, AstraZeneca, and Lilly; and consultant fees from Sanofi. Dr Carlson reported receipt of grants from Novo Nordisk, Medtronic, Insulet, Sanofi, Dexcom, Abbott, Lilly, and UnitedHealth; he reports contracts as a research investigator and/or consultant through his employer, HealthPartners Institute/International Diabetes Center at Park Nicollet (with no personal income received), with Novo Nordisk, Medtronic, Insulet, Sanofi, Abbott, Sensionics, and Lilly; in addition, Dr Carlson has a patent to US Provisional Patent Application Serial No. 62/443 004 pending. Dr Chaytor reported receipt of personal fees from Lilly. Dr Kruger reported receipt of grants and personal fees from Dexcom. Dr Levy reported receipt of nonfinancial support from Dexcom. Dr McGill reported receipt of personal fees from Aegerion, Bayer, Boehringer Ingelheim, Gilead, Lilly, Metavant, Valeritas, Janssen, Mannkind, the Endocrine Society, the American Association of Clinical Endocrinologists, Culinary Medicine, Novo Nordisk, and Dexcom; grants from Novo Nordisk, Dexcom, Medtronic, Novartis, AstraZeneca, and the NIH; and nonfinancial support from Bayer, Boehringer Ingelheim, the American Association of Clinical Endocrinologists, Mannkind, Culinary Medicine, and the Jaeb Center for Health Research. Dr Peters reported receipt of personal fees from Medscape, Sanofi, Lexicon, Becton Dickinson, Abbot Diabetes Care, Bigfoot, Mannkind, Novo Nordisk, Lilly, and Boehringer Ingelheim; grants from AstraZeneca, vTv Therapeutics, Mannkind, and Dexcom; and stock options for Mellitus Health, Omada Health, Stability Health, Pendulum Therapeutics, and Livongo. Dr Shah reported receipt of consulting fees through the University of Colorado from Dexcom and grants from vTv therapeutics, Novo Nordisk, Mylan GmbH, Sanofi US Services Inc, Insulet, and the NIH. Dr Weinstock reported receipt of grants from the Juvenile Diabetes Research Foundation, Insulet Corporation, Tolerion Inc, Lilly, Medtronic, Diasome Pharmaceuticals, Boehringer Ingelheim, Oramed Ltd, and Mylan GmbH and personal fees from Insulogic. Dr Miller reported receipt of nonfinancial support from Dexcom and Tandem. No other disclosures were reported.

Figures

Figure 1.. Flow of Participants in the Wireless Innovation for Seniors With Diabetes Mellitus (WISDM) Study

Enrollment took place from September 2017 to May 2018, and study follow-up for the randomized trial continued through December 2018. BGM indicates blood glucose monitoring; CGM, continuous glucose monitoring. aInformation on patients screened but not enrolled was not collected. bOne patient was excluded for having both a history of at least 1 severe hypoglycemia event in the past 6 months and spending more than 10% of time with CGM glucose levels less than 54 mg/dL during the blinded prerandomization phase. cTwo participants in the standard BGM group initiated real-time CGM before completing the 26-week visit. dOne participant in the CGM group and 6 participants in the standard BGM group were missing CGM data at follow-up. Missing data were handled using direct likelihood. Baseline data for these participants were included in the model.

Figure 2.. Percentage of Time Spent With Less Than 70 mg/dL by Study Visit and Time of Day

To convert glucose values to millimoles per liter, multiply by 0.0555. A, By study visit: tops and bottoms of boxes indicate 25th and 75th percentiles; lines, medians; solid cirles, means; whiskers, minimums and maximums after removing outliers; and open circles, outliers. B, By time of day: thinner lines indicate 25th and 75th percentiles and thicker lines, medians. Participants with follow-up continuous glucose monitoring data had a minimum of 48 readings and maximum of 420 readings used to calculate percentage of time spent with glucose levels less than 70 mg/dL for each hour of the day.