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Type 2 diabetes
Marc Y Donath
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3
Urinary glucose excretion via SGLT2 inhibition
SGLT2
SGLT2inhibitor
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Glukosurie / Tag mit SGLT2i50-80 g Glucose = 200-320 Kalorien =
12 – 20 Zuckerwürfeln
Cardiomyocytes
Control Glucose
Dyntar et al. Diabetes 50: 2105-13
Type 2 diabetes=
Protection against Overnutrition
Islet:Protection
= Insulin production↓
Fat, liver, muscle:Protection
= Insulin sensitivity ↓
Kidney:Protection
= Glucosuria
Glucose disposal:HbA1c reflects only glycemia
Nash
Obesity
Retinopathy
Heart failure
Nephropathy
Donath et al, Nature Reviews Immunology, 2019
Outcome from anti-diabetic drugsMacro-
vascularHeart failure
CKD Retinopathy NASH Diabetes progression
SGLT2i - + + ? ? ?GLP1a + - - ? ? ?DPP-IVi - - - ? ? ?SU harm ? harm ? - ? ? ?Anti-IL-1β + + ? (+) ? +
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Therapeutic scheme
1.Lifestyle2.Metformin (?)3. Individualization :
A. Early case: GLP-1a (BMI>28), SGLT2i (or DPP4i ?) B. Established cardiovascular disease: SGLT2i (heart failure) GLP-1a (obese)
C. Aging: SGLT2iD. Lean, Uncontrolled diabetes or GFR < 30 : Basal insulin E. BMI>35 (with diabetes>30?): consider bariatric surgery
Lifestyle
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GLP-1 analogaDaily Liraglutide:
Victoza Saxenda (obesity dosing) Xultophy (Liraglutide & Insulin-Degludec)
Lixisenatid Lyxumia Suliqua (Lixisenatid & Insulin-Glargin)
Once‐weekly Exenatide Once Weekly Sustained-release
Bydureon Dulaglutide
Trulicity Semaglutide
Ozempic
Oral Semaglutide
Rybelsus
• HbA1c↓• Body weight ↓( 80-100 gr. glucose = ~ 300-400 cal/day) • Blood pressure ↓• No hypoglyceamia• All combination possible (incretin limits)
BUT: • Genital infections• Ketoacidosis
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SGLT2 Inhibitors
SGLT2 Inhibitors• Empagliflozin
• Jardiance• Canagliflozin
• Invokana• Dapagliflozin
• Forxiga• Ertugliflozin
• Steglatro
Patient, 79 year old:
- BMI 22- HbA1c 10.6%- Heart failure- Treated with Metformin and Sitagliptin
Patient, 79 year old:
- BMI 22- HbA1c 10.6%- Heart failure- Treated with Metformin and Sitagliptin
Stop SitagliptinStart SGLT2 inhibition
Patient, 77 year old:
- BMI 28- HbA1c 6.6%- MI 10 years ago- Feels well- Treated with Metformin and Sitagliptin
Patient, 77 year old:
- BMI 28- HbA1c 6.6%- MI 10 years ago- Feels well- Treated with Metformin and Sitagliptin
Stop SitagliptinStart SGLT2 inhibition
Patient, 52 year old:
- BMI 29- HbA1c 6.2%- MI 3 years ago- Treated with Metformin
Patient, 52 year old:
- BMI 29- HbA1c 6.2%- MI 3 years ago- Treated with Metformin
Ad GLP-1 agonistConsider combination with SGLT2 inhibition
Patient, 47 year old:
- Polyuria & polydipsia for 3 weeks- BMI 28- HbA1c 14.8%- Urin keton bodies ++++
Patient, 47 year old:
- Polyuria & polydipsia for 3 weeks- BMI 34- HbA1c 14.8%- Urin keton bodies ++++
Saline & lifestyle intervention
Patient, 45 j:Diabetes Typ 2, ED 06.04.20:- 136 Kg- Glucose 25.0 mmol/l- HbA1c 14.3 % - Ketonkörper ++++
Patient, 45 j:Diabetes Typ 2, ED 06.04.20:- 136 Kg- Glucose 25.0 mmol/l- HbA1c 14.3 % - Ketonkörper ++++Lifestyle intervention1 Monat Lantus (lockdown)Ozempic30.6.21:- 100 Kg- HbA1c 5.2 %
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