Continuous glucose monitoring - proved hypoglycemia in sodium-glucose co-transporter-2 inhibitors - treated type 2 diabetes patients: a link to ketosis development

  • Authors: Levit S. 1,2, Giveon S. 3, Musin I.N. 2, Barnea R. 4, Korek-Abadi I. 5, Levit V. 6, Ryder D. 7, Ryder C. 7,8,9
  • Affiliations:
    1. Institute of Endocrinology, Diabetes & Metabolism, Assuta Medical Center, Tel-Aviv, Israel
    2. National Research Technological University, Kazan, Russia
    3. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
    4. Assuta Research Institute, Assuta Medical Center, Tel-Aviv, Israel
    5. Department of Academy and Research, Assuta Medical Center, Tel-Aviv, Israel.
    6. Department of Disease prevention, City Clinical Hospital №8, Chelyabinsk, Russia
    7. Virtual-Reality & Neuro Cognition Lab, Technion – Israel Institute of Technology, Haifa, Israel
    8. Brain Research Laboratory, Department of Neurology, Ziv Medical Center, Safed, Israel
    9. Faculty of Medicine, Bar-Ilan University, Safed, Israel
  • Issue: Vol 1, No 1 (2019)
  • Pages: 52-69
  • Section: Biomedical Sciences
  • URL:
  • DOI:
  • Cite item


Background: Latest studies have shown the remarkable ability of sodium-glucose co-transporter-2 inhibitors (SGLT2i) to reduce cardiovascular morbidity and mortality. However, real-life data and the results of several other studies seem to contradict these outcomes, pointing out possibilities of serious side effects. Ketoacidosis (KA) remains one of the most dangerous complications, yet, not fully understood. All of the above urgently requires real-practice data, which may shed some light on side effects of this novel anti-diabetic drug family.

Aims: To investigate the real-life rates of hypoglycemia and ketosis (K) in SGLT2i treated patients, using Continuous Glucose Monitoring (CGM) and capillary blood β-hydroxybutyrate measurements.

Methods: We report the results of a two-year retrospective analysis of 136 Type 2 Diabetes (T2DM) patients, all (100%) treated with a SGLT2i, combined with Metformin or Metformin with Incretin-Based therapy (MT-IBT). CGM recordings were done in 52 persons. In 9 patients (Group A), CGM-proved hypoglycemic episodes were discovered. The rest of 43 patients (Group B) didn’t show any hypoglycemia. Three patients in Group A and 11 from Group B were also treated with small doses of basal insulin on admission; the insulin was later discontinued in all patients of Group A and seven patients of Group B . Main characteristics of two groups were subsequently compared.

Results: CGM data analysis showed significantly lower average Sensor Glucose (SG) , 7.2±1.3 vs. 8.2±1.7 mmol/l, p=0.04, and estimated HbA1c , 6.1±0.7 vs. 6.8±1.1%, p=0.02, in Group A patients.

We also report three cases of ketosis, proved by elevated capillary β-hydroxybutyrate concentrations. Pathophysiological link between frequent hypoglycemia rates (Six patients without insulin treatment (11.5 % in total CGM group of 52 patients)) and ketosis development (Three patients (2.2% in total cohort of 136 participants)) was suggested.

Conclusions: More frequent than previously reported rates of hypoglycemia and ketoacidosis were discovered in patients taking SGLT2 inhibitors. Pathophysiological link between the two conditions is assumed. More studies are needed to confirm our hypothesis.

About the authors

Shmuel Levit

Institute of Endocrinology, Diabetes & Metabolism, Assuta Medical Center, Tel-Aviv, Israel;
National Research Technological University, Kazan, Russia

Author for correspondence.
ORCID iD: 0000-0003-0406-8021

Israel, Street, Tel-Aviv 6971028, Israel; st. Karl Marx, 68, Kazan, Republic of Tatarstan, 420015, Russia

MD, PhD, Professor, Head of Institute of Endocrinology, Diabetes & Metabolism, Assuta Medical Center; Professor of Kazan National Research Technological University, Russian Federation

Shmuel Giveon

Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

ORCID iD: 0000-0002-3638-0055

Israel, Tel-Aviv, Israel

Doctor of Medical Sciences, Master of Health, Head of Research

Ildar N. Musin

National Research Technological University, Kazan, Russia

ORCID iD: 0000-0003-4516-4183

Israel, Karl Marx str., 68, Kazan, Republic of Tatarstan, 420015, Russia

PhD. of Engineering Science, Head of the Department of medical Informatics

Royi Barnea

Assuta Research Institute, Assuta Medical Center, Tel-Aviv, Israel

ORCID iD: 0000-0002-6119-9725

Israel, street Habarzel 20. Tel-Aviv 6971028, Israel

PhD, Chief investigator, Assuta Health Services Research Institute, Assuta Medical Centers Network

Ifat Korek-Abadi

Department of Academy and Research, Assuta Medical Center, Tel-Aviv, Israel.

ORCID iD: 0000-0002-2771-8819

Israel, street Habarzel 20. The 6971028 Tel Aviv, Israel

PhD, Academic and research director, Department of Academy and Research, Assuta Medical Center, Assuta Medical Centers Network

Vyacheslav Levit

Department of Disease prevention, City Clinical Hospital №8, Chelyabinsk, Russia

ORCID iD: 0000-0003-1306-1374

Russian Federation, Chelyabinsk, Gorky street, 18

MD, Head of Disease Prevention Department

Darian Ryder

Virtual-Reality & Neuro Cognition Lab, Technion – Israel Institute of Technology, Haifa, Israel

ORCID iD: 0000-0001-9691-7136

Israel, Haifa, 3200003


Chen Hanna Ryder

Virtual-Reality & Neuro Cognition Lab, Technion – Israel Institute of Technology, Haifa, Israel;
Brain Research Laboratory, Department of Neurology, Ziv Medical Center, Safed, Israel;
Faculty of Medicine, Bar-Ilan University, Safed, Israel

ORCID iD: 0000-0002-9028-1154

Israel, Henrietta Szold St 8, Safed, Israel

PhD, Principal Investigator, Head of the Brain Research Laboratory, Department of Neurology, Ziv Medical Center


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Copyright (c) 2019 Levit S., Giveon S., Musin I.N., Barnea R., Korek-Abadi I., Levit V., Ryder D., Ryder C.

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