Continuous Glucose Monitoring Profiles and Health Outcomes after Dapagliflozin Plus Saxagliptin vs Insulin Glargine

Donald C Simonson; Marcia A Testa; Ella Ekholm; Maxwell Su; Tina Vilsbøll; Serge A Jabbour; Marcus Lind

doi:10.1210/clinem/dgae105

Continuous Glucose Monitoring Profiles and Health Outcomes after Dapagliflozin Plus Saxagliptin vs Insulin Glargine

J Clin Endocrinol Metab. 2024 Feb 27:dgae105. doi: 10.1210/clinem/dgae105. Online ahead of print.

Authors

Donald C Simonson¹, Marcia A Testa^{2

3}, Ella Ekholm⁴, Maxwell Su^{2

3}, Tina Vilsbøll^{5

6}, Serge A Jabbour⁷, Marcus Lind^{8

9

10}

Affiliations

¹ Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
³ Phase V Technologies, Inc., Wellesley Hills, MA, USA.
⁴ AstraZeneca R&D, Gothenburg, Sweden.
⁵ Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark.
⁶ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷ Thomas Jefferson University, Philadelphia, PA, USA.
⁸ Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
⁹ Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁰ Department of Medicine, NU-Hospital Group, Trollhättan and Uddevalla, Sweden.

PMID: 38412282
DOI: 10.1210/clinem/dgae105

Abstract

Context: Glycemic variability and hypoglycemia during diabetes treatment may impact therapeutic effectiveness and safety, even when glycated hemoglobin (HbA1c) reduction is comparable between therapies.

Objective: We employed masked continuous glucose monitoring (CGM) during a randomized trial of dapagliflozin plus saxagliptin (DAPA+SAXA) vs insulin glargine (INS) to compare glucose variability and patient-reported outcomes (PROs).

Design: 24-week sub-study of a randomized, open-label, two-arm, parallel-group, phase 3b study.

Setting: Multicenter study (112 centers in 11 countries).

Patients: 283 adults with type 2 diabetes (T2D) inadequately controlled with metformin ± sulfonylurea.

Interventions: DAPA+SAXA vs INS.

Main outcome measures: Changes in CGM profiles, HbA1c, and PROs.

Results: Changes from baseline in HbA1c with DAPA+SAXA were similar to those observed with INS, with mean difference [95% CI] between decreases of -0.12% [-0.37 to 0.12%], P = .33. CGM analytics were more favorable for DAPA+SAXA, including greater percent time in range (> 3.9 and ≤ 10 mmol/L; 34.3 ± 1.9 vs 28.5 ± 1.9%, P = .033), lower percent time with nocturnal hypoglycemia (area under the curve ≤ 3.9 mmol/L; 0.6 ± 0.5 vs 2.7 ± 0.5%, P = .007), and smaller mean amplitude of glycemic excursions (-0.7 ± 0.1 vs -0.3 ± 0.1 mmol/L, P = .017). Improvements in CGM were associated with greater satisfaction, better body weight image, less weight interference, and improved mental and emotional well-being.

Conclusions: DAPA+SAXA and INS were equally effective in reducing HbA1c at 24 weeks, but people with T2D treated with DAPA+SAXA achieved greater time in range, greater reductions in glycemic excursions and variability, less time with hypoglycemia, and improved patient-reported health outcomes.

Keywords: continuous glucose monitoring; dapagliflozin; insulin glargine; quality of life; saxagliptin; type 2 diabetes.