Gravicentric approach to Type 2 Diabetes therapy. The success prediction. A proof-of-concept

  • Authors: levit S.1,2, Torban N.3, Boaz M.4,5, Weichman M.6, Azuri J.7,8, Manisterski Y.9,10, Merzon E.11,8, Ryder D.1, Ginossar G.12, Gavra T.13, Levit V.14, Domuschiev I.15, Musin I.2, Ryder C.H.16,17
  • Affiliations:
    1. Endocrinology and Diabetology Institute affiliated to Assuta Medical Center, Tel Aviv, Israel
    2. Kazan National Research Technological University, Kazan, Russia
    3. Institute of Endocrinology, Diabetes & Metabolism, Assuta Medical Center, Tel Aviv, Israel
    4. Department of Nutrition, School of Health Sciences, Ariel University Ariel, Israel
    5. Epidemiology and Research Unit, E. Wolfson Medical Center, Holon, Israel
    6. Maccabi Health Foundation, Petah – Tiqwa, Israel
    7. Maccabi Healthcare Services
    8. Lecturer of Sackler Faculty of Medicine, Tel Aviv, Israel
    9. Maccabi Health Foundation
    10. Petah – Tiqwa, Israel
    11. Leumit Health Foundation, Tel Aviv, Israel
    12. Urgent Care Consultant the Royal London Hospital, A&E and Urgent Care Centre, London, United Kingdom
    13. Assuta Medical Centers, Tel Aviv University, Tel Aviv, Israel
    14. City Clinical Hospital No8, Chelyabinsk, Russia
    15. Multiprofile Hospital for active treatment “St. Panteleimont”, Sofia, Bulgaria
    16. Department of Neurology, Ziv Medical Center, Safed, Israel
    17. Department of Criminology, Western Galilee College, Acre, Israel
  • Issue: Vol 2, No 2 (2020)
  • Pages: 48-60
  • Section: Biomedical Sciences
  • URL: https://journals.eco-vector.com/PharmForm/article/view/34728
  • DOI: https://doi.org/10.17816/phf34728
  • Cite item

Abstract


This study is the proof-of-concept of our "Gravicentric" theory. This concept is based on several fundamental points: obesity as the main foe; rapid reversibility of the disease; as well as a new perspective on the roles different pharmacological classes play in general, and the role of insulin and GLP-1 analogs, in particular. The paper presents and discusses our experience of the implementation of insulin and GLP-1 analogs. The possibility of "insulin weaning"; the therapeutic approach for over-treated patients; and physiological dosing of insulin is also discussed therein.

Objectives

Primary: To evaluate the long-term efficacy of GLP-1 analogs in insulin-treated Type 2 Diabetes Mellitus (T2DM) patients.

Secondary: To analyze which patient would most likely benefit from this combined treatment.

Methods

In 54 T2DM patients with a mean disease duration of 17.5 years and a mean extent of insulin therapy of 4.5 years, additional GLP-1 analogs therapy was prescribed. Mean duration of GLP-1 treatment was 25.8 months (2.15 years).

During the intervention, clinical, biochemical, and anthropometric parameters were analyzed. Compliance, Hypoglycemia and Metabolic Index (MI) assessments were implemented.

Results

Mean Glycated hemoglobin (HbA1C) decreased from 9.28 ± 1.43 to 8.54 ± 1.4% on GLP-1 analogs, p < 0.01. Total Daily dose of Insulin (TDI) showed considerable reduction: 80.6 ± 42.7 U/day before starting GLP-1 vs.41.0 ± 30.7 U/day on GLP-1, p< 0.01. These changes were directly linked to weight loss: BMI has dropped from 35.1 ± 4.8 kg/cm2 before, to 32.8 ± 5.0 kg/cm2 on GLP-1 analogs, with patients losing 6.7 kg on average. Moreover, 13 (24%) participants discontinued at least one kind of insulin, while 7 (13%) stopped taking insulin completely, with simultaneous improvement in diabetes control. No clinically significant hypoglycemia was observed.

Post-hoc, the participants were categorized according to each patient’s ability to reduce TDI by more than 20 U/day, and then split into two groups. Group A – 34 patients (64.2%) who successfully reduced TDI; Group B – 19 patients (35.8%) who failed to do so. The comparison of the two groups showed the following:

  1. Significantly larger – virtually twice as large – baseline TDI in Group A (97.4±40.4 U/day vs. 52.2±31.0 U/day), p< 0.001.
  2. Very effective BMI reduction (ΔBMI 3.3 ± 2.4 kg/cm2 0.9 ± 1.2 kg/cm2, p< 0.001) and much better compliance (1.4 ± 1.1 vs. 2.2 ± 1.0, p< 0.02) in Group A.
  3. A considerable decline of insulin requirements in group A, on GLP-1 therapy (ΔTDI on GLP-1 was -62.4 ± 31.9 U/day) with no TDI reduction in Group “B” (ΔTDI on GLP-1 was +0.03 ± 14.1 U/day, p< 0.001).

Thus, in spite of the fact that on GLP1 therapy HbA1C has declined to the same levels in both groups, patients from group A became much leaner and metabolically healthier.

We suggest overtreatment as the critical factor of obesity in Group A.

Conclusions

Adding GLP-1 analogs to insulin in poorly controlled, insulin-treated T2DM patients resulted in an impressive weight (BMI) reduction with significant improvements in glucose control. This provided for a further decline in insulin resistance and insulin requirements. We suggest that the best candidate for successful GLP-1 analogs therapy is an obese, overtreated and compliant T2DM person. Changes in Metabolic Index (MI) rather than surrogate glycemic parameters (HbA1C) are better predictors of a successful T2DM therapy. Neither the duration of diabetes nor the length of insulin therapy in the past is likely to have a critical role in predicting success. These findings are proof-of-concept of our Gravicentric theory in T2DM.


About the authors

Shmuel levit

Endocrinology and Diabetology Institute affiliated to Assuta Medical Center, Tel Aviv, Israel; Kazan National Research Technological University, Kazan, Russia

Author for correspondence.
Email: prof@levitsh.co.il
ORCID iD: 0000-0003-0406-8021

Israel

Доктор медицинских наук, профессор, заведующий НИИ эндокринологии, диабета и метаболизма, медицинский центр "Ассута"; профессор Казанского национального исследовательского технологического университета, Российская Федерация

Naum Torban

Institute of Endocrinology, Diabetes & Metabolism, Assuta Medical Center, Tel Aviv, Israel

Email: drtorban@levitsh.co.il
ORCID iD: 0000-0001-8891-1711

Israel, ул. ул. Ха-Нехошет, 10, Тель-Авив 6971028, Израиль

MD, endocrinologist

Mona Boaz

Department of Nutrition, School of Health Sciences, Ariel University Ariel, Israel; Epidemiology and Research Unit, E. Wolfson Medical Center, Holon, Israel

Email: mboaz8@yahoo.com
ORCID iD: 0000-0002-3920-7549

Israel

Ph.D., Professor, Department of Nutrition

Maria Weichman

Maccabi Health Foundation, Petah – Tiqwa, Israel

Email: mariahdiet@gmail.com
ORCID iD: 0000-0002-9822-8489

Israel

Specialist in clinical dietology

Joseph Azuri

Maccabi Healthcare Services; Lecturer of Sackler Faculty of Medicine, Tel Aviv, Israel

Email: Azuri_yo@mac.org.il
ORCID iD: 0000-0003-1049-9848

Israel

MD, Specialist in Family medicine, a member of the research department

 

Yossi Manisterski

Maccabi Health Foundation; Petah – Tiqwa, Israel

Email: manister_y@mac.org.il
ORCID iD: 0000-0002-7420-6875

Israel

MD, Director of Institute of Diabetes

Eugene Merzon

Leumit Health Foundation, Tel Aviv, Israel; Lecturer of Sackler Faculty of Medicine, Tel Aviv, Israel

Email: emarzon@leumit.co.il
ORCID iD: 0000-0001-5469-0236

Israel

MD, Director of Diabetes service, Lecturer of Sackler Faculty of Medicine

Darian Ryder

Endocrinology and Diabetology Institute affiliated to Assuta Medical Center, Tel Aviv, Israel

Email: Darian@Neurologit.com
ORCID iD: 0000-0001-9691-7136

Israel

PhD, Senior Data Scientist

Gideon Ginossar

Urgent Care Consultant the Royal London Hospital, A&E and Urgent Care Centre, London, United Kingdom

Email: Ginossarg@gmail.com
ORCID iD: 0000-0003-2193-6230

United Kingdom

MD, Senior physician

Tali Gavra

Assuta Medical Centers, Tel Aviv University, Tel Aviv, Israel

Email: talig@assuta.co.il
ORCID iD: 0000-0003-2938-2682

Israel

Research Unit Director

Vyacheslav Levit

City Clinical Hospital No8, Chelyabinsk, Russia

Email: slava_levit@mail.ru
ORCID iD: 0000-0003-1306-1374

Russian Federation

MD, Head of Disease Prevention Department

Ivan Domuschiev

Multiprofile Hospital for active treatment “St. Panteleimont”, Sofia, Bulgaria

Email: vopsi@abv.bg
ORCID iD: 0000-0002-7885-0668

Bulgaria

MD, Specialist endocrinologist

Ildar Musin

Kazan National Research Technological University, Kazan, Russia

Email: ildarmusin@mail.ru
ORCID iD: 0000-0003-4516-4183
Scopus Author ID: 57193350975
ResearcherId: V-3175-2017

Russian Federation

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

Chen Hanna Ryder

Department of Neurology, Ziv Medical Center, Safed, Israel; Department of Criminology, Western Galilee College, Acre, Israel

Email: chenryder1@gmail.com
ORCID iD: 0000-0002-9028-1154

Israel

PhD, Principal Investigator, Lecturer and Researcher

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