Use of flash glucose monitoring is associated with HbA1c reduction in type 2 diabetes managed with basal insulin in Canada: A real-world prospective observational study

Abstract

Dear editor,

The global prevalence of type 2 diabetes mellitus (T2DM) is estimated to reach 12% by 2045, driving the condition to become one of the most challenging health problems of the 21st century.¹ An estimated 30% of people living with T2DM are managed with insulin but a significant proportion of these people are unable to achieve adequate glycaemic control as measured by HbA1c.² This highlights the need for additional strategies for glycaemic optimisation. Several studies have demonstrated the benefit of continuous glucose monitoring (CGM) systems in T2DM. However, this reported benefit is mostly based on studies in people treated with intensive insulin regimens.^3,4 The evidence supporting CGM use in those managed with a basal insulin-only regimen is limited.⁵

We conducted a prospective, observational, non-interventional cohort study across nine clinical centres in Canada to evaluate the impact of commencing intermittently scanned (also known as ‘flash’) CGM on HbA1c in T2DM managed with basalinsulin-only regimens. Sites searched medical records to identify adults aged 18 years or over with T2DM managed with a basal insulin-only regimen for at least 1 year and who had commenced using FreeStyle Libre/Libre 2 (Abbott Diabetes Care, Witney, UK) within the last 3 months or were planning to start in the next 30 days. Patients with an HbA1c recorded in their medical records between 8.0 – 12.0% (64 – 108 mmol/mol) within 3 months prior to starting FreeStyle Libre/Libre 2 (or within 3 months prior to baseline data collection if device use had not started) were included. Key exclusion criteria were patients receiving or planning dialysis, patients prescribed corticosteroid therapy and female patients who were pregnant or planning pregnancy. Sites subsequently collected data at 3 – 6 months (85 – 199 days) for follow-up HbA1c levels and changes to diabetic medication. The primary outcome was evaluation of change in HbA1c from baseline to 3 – 6 months after initiating device use. Secondary outcomes included changes to non-insulin glucose lowering medications, insulin regimens and doses. A paired t-test was used to compare HbA1c values and insulin doses between baseline and 3 – 6 months. McNemar’s test was used to compare the proportions of patients using each class of medication between baseline and 3 – 6 months.⁶

Of the 132 patients who met the eligibility criteria at baseline, 79 were included into the final analysis. Most exclusions after baseline data collection were due to a lack of follow-up HbA1c in the prespecified time period (n = 44). From a baseline HbA1c of 8.9 ± 0.8% (74 ± 9 mmol/mol) (mean ± SD), a significant reduction of 0.6 ± 1.1% (7 ± 12 mmol/mol) was observed at 3 – 6 months, p < .0001 (Table 1). This improvement was observed regardless of baseline HbA1c (<9.0% (<75 mmol/mol), p = .0193 and ≥9.0% (≥75 mmol/mol), p < .0001), age (<65 years, p = .0050 and ≥65 years p < .0001), sex (male, p = .0008 and female, p = .0006), duration of insulin use (<4 years, p = .0188 and ≥4 years, p < .0001) or baseline BMI (<30 kg/m², p = .0016 and ≥30 kg/m², p = .0017). The observed change in HbA1c was greater in those with baseline HbA1c ≥9.0% (≥75 mmol/mol) (mean ± SD change −1.1 ± 1.2% (−13 ± 13 mmol/mol) versus −0.3 ± 0.8% (−3 ± 9 mmol/mol) for baseline HbA1c <9.0% (<75 mmol/mol)).

Table 1.

Summary of patient characteristics at baseline and at the study endpoint, 3 – 6 months following commencement of flash glucose monitoring. (n = 79).

	Baseline	End of study	Change	p
Mean age ± SD (years)	67.3 ± 11.5
Sex, male	43 (54%)
Mean BMI ± SD (kg/m²)	30.1 ± 6.2 (n = 65)
Mean HbA1c ± SD (%)	8.9 ± 0.8	8.3 ± 1.0	−0.6 ± 1.1	<.0001
Mean HbA1c ± SD (mmol/mol)	74 ± 9	67 ± 11	−7 ± 12	<.0001
Duration of insulin use (years)	5.3 ± 3.9 (n = 74)
Mean total daily dose of basal insulin ± SD (units)
All patients	36.3 ± 29.9	32.9 ± 28.2	−3.4 ± 13.7	.0297
Excluding patients who started bolus insulin (n = 76)	36.0 ± 30.3	32.5 ± 28.4	−3.5 ± 13.9	.0328

	Baseline	End of study	Stopped	Started	p
Non-insulin glucose lowering medication (n)	78 (99%)	79 (100%)
Metformin	69 (87%)	69 (87%)	3 (4%)	3 (4%)	1.0000
Sulphonylureas	37 (47%)	41 (52%)	0	4 (5%)	.1250
SGLT-2 inhibitors	49 (62%)	51 (65%)	3 (4%)	5 (6%)	.7266
DPP-4 inhibitors	19 (24%)	13 (16%)	6 (8%)	0	.0313
GLP-1 RAs	35 (44%)	41 (52%)	4 (5%)	10 (13%)	.1796
Thiazolidinediones	3 (4%)	3 (4%)	0	0	—
Meglitinides	4 (5%)	3 (4%)	1 (1%)	0	1.0000

SD: standard deviation; BMI: body mass index; SGLT-2: sodium-glucose transporter; DPP-4: dipeptidyl peptidase 4; GLP-1 RA: glucagon-like peptide 1 receptor agonist. Bold indicates p < .05.

The mean total daily dose of basal insulin decreased by 3.4 ± 13.7 units (9%) at 3 – 6 months, p = .0297. Use of dipeptidyl peptidase 4 (DPP-4) inhibitors significantly reduced from 24.1% at baseline to 16.5%, p = .0313. Upon further investigation, it was found that all 6 patients who stopped using DPP-4 inhibitors started glucagon-like peptide-1 receptor agonists (GLP-1 RAs). There were no significant changes in other non-insulin glucose lowering medications by the study endpoint.

Our findings support a previous multicentre retrospective observational study performed in Canada which demonstrated an HbA1c reduction of 0.8% at 3 – 6 months in people with T2DM using basal insulin-only regimens.⁷ Three further retrospective studies in the USA observed HbA1c reductions between 0.6 – 1.4% in basal insulin-only treated populations following flash glucose monitoring initiation.^8–10 Findings from these observational studies are further supported by a randomised controlled trial (RCT) which demonstrated an adjusted HbA1c difference of −0.4% at 8 months between those using CGM compared to those performing capillary blood glucose monitoring (CBGM).¹¹ Conversely, discontinuation of CGM after 8 months of use demonstrated a trend towards worsening HbA1c 6 months after discontinuation.¹²

Importantly, this study demonstrated a concurrent reduction in basal insulin dose at follow-up. In the aforementioned RCT, there was neither a significant difference in basal insulin dose between those using CGM compared to those performing CBGM nor any reduction in dose in the CGM arm by the study end point.¹¹ A reduction in insulin dose may have been facilitated through flash glucose monitoring encouraging lifestyle changes which led to better glycaemic control.¹³ Additionally, the device may have revealed episodes of hypoglycaemia which were previously unseen through CBGM thereby leading to reductions in insulin doses.¹⁴

We acknowledge that a significant proportion of patients were excluded from the final analysis due to a lack of follow-up HbA1c. This may be due to this study being conducted following the Covid-19 pandemic, which led to backlogs on diabetes services globally and potentially delayed the timely collection of routine blood tests.¹⁵ Nevertheless, our study adds to a growing body of evidence demonstrating the benefit of flash glucose monitoring in people with T2DM on non-intensive insulin regimens.

Footnotes

Acknowledgements

The authors would like to thank Randeep S Heer (Scientific Affairs Manager, Abbott Diabetes Care, UK) for medical writing support, Zoë Welsh and Joshua Lovegrove for statistical support (Statistics, Abbott Diabetes Care, UK), and the many individuals involved in data collection at study sites.

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AA reports grants from Abbott related to the submitted work. AA also reports grants, advisory and speaking fees outside of the submitted work from Abbott, Amgen, Bayer, Novo Nordisk, Janssen, AstraZeneca, Eli Lilly, Boehringer-Ingelheim, Medtroni, Moderna, Senseonics, Dexcom, Insulet, Glaxo-Smith-Kline, Lexicon, Pfizer, and Zucara. ABJ reports research grants, speaking or consulting honoraria from Abbott, Amgen, Novo Nordisk, Acerus, AstraZeneca, Bausch Healthcare, Bayer, Boehringer Ingelheim, Care to Know, CCRN, Connected in Motion, CPD Network, Dexcom, Diabetes Canada, Eli Lilly, Gilead, GSK, HLS Therapeutics, Insulet, Janssen, Master Clinician Alliance, MDBriefcare, Merck, Medtronic, Moderna, Novartis, Novo Nordisk, Partners in Progressive Medical Education, Pfizer, PocketPills, Roche, Sanofi, Takeda, Timed Right and WebMD. MAT reports speaking honoraria from Abbott, NovoNordisk, Eli Lilly, Boehringer-Ingelheim and Janssen. BPG reports speaking honoraria from Abbott, Dexcom and Pfizer as well as consulting honoraria from Abbott, Amgen, Boehringer Ingelheim, Novo Nordisk and Pfizer. JL reports research grants, speaking or consulting honoraria from Abbott, Eli Lilly, Boehringer Ingelheim, Novo Nordisk, Canadian Collaborative Research Network, AstraZeneca and Dexcom. KQ reports speaking or consulting honoraria from Novo Nordisk, Astra Zeneca and Bausch Health. VCW reports speaking honoraria and/or advisory board roles for Abbott, Dexcom, Novo Nordisk and Eli Lilly. CC and JS report no relevant disclosures.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Abbott Diabetes Care, Witney, UK in collaboration with the corresponding author designed the study protocol. Abbott Diabetes Care funded the resources for conducting this study, but no devices were provided to the study sites or individuals in the study. Abbott Diabetes Care was involved in data collection, analysis, and reporting but did not participate in the authors’ interpretation of study results.

Ethical statement

Contributorship

The corresponding author was involved in the design of the study protocol and preparation of the first draft of the manuscript. All authors were involved in the editing and approval of the final manuscript. All authors had full access to the study data and take complete responsibility for the integrity of the data and accuracy of the data analysis.

ORCID iD

Alexander Abitbol

Data availability statement

The data sets analysed for this manuscript are available from the corresponding author upon reasonable request.*

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