Diabetes Metab J.  2021 May;45(3):339-348. 10.4093/dmj.2019.0203.

Effect of Dapagliflozin as an Add-on Therapy to Insulin on the Glycemic Variability in Subjects with Type 2 Diabetes Mellitus (DIVE): A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 2Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea.
  • 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
  • 5Department of Endocrinology and Metabolism, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
  • 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea.
  • 7Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 8MedicalExcellence Inc., Seoul, Korea.

Abstract

Background

Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.

Methods

In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).

Results

At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, P<0.001), glycated albumin (−3.94%±2.55% vs. −0.67%±2.48%, P<0.001), and CGM-derived mean glucose (−41.6±39.2 mg/dL vs. 1.1±46.2 mg/dL, P<0.001) levels were observed in the dapagliflozin group compared with the placebo group. SD and MAGE were significantly decreased in the dapagliflozin group, but not in the placebo group. However, the difference in ΔSD and ΔMAGE failed to reach statistical significance between two groups. No significant differences in the incidence of safety endpoints were observed between the two groups.

Conclusion

Dapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.


Keyword

Dapagliflozin; Diabetes mellitus; Randomized controlled trial; Sodium-glucose transporter 2 inhibitors

Figure

  • Fig. 1 (A) Glycosylated hemoglobin (HbA1c) and (B) glycated albumin levels recorded during the study. Values are presented as mean±standard deviation. aP<0.05 for the comparison between groups.

  • Fig. 2 (A) Mean glucose levels, (B) standard deviation, and (C) mean amplitude of glycemic excursion (MAGE) derived from continuous glucose monitoring. The right panel shows individual plots from participants. Values are presented as mean±standard deviation. aP<0.05.

  • Fig. 3 Percentage of time in which glucose levels were within the target range, hyperglycemia, and hypoglycemia in the (A) placebo and (B) dapagliflozin groups. aP<0.05 compared with baseline, bP<0.05 compared with the placebo group.


Cited by  2 articles

Time in Range from Continuous Glucose Monitoring: A Novel Metric for Glycemic Control
Jee Hee Yoo, Jae Hyeon Kim
Diabetes Metab J. 2020;44(6):828-839.    doi: 10.4093/dmj.2020.0257.

Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes
Min Jeong Park, Kyung Mook Choi
Diabetes Metab J. 2022;46(1):49-62.    doi: 10.4093/dmj.2021.0316.


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