SGLT2 inhibitors - what's new?
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This document summarizes recent developments with SGLT2 inhibitors. It discusses their use in non-diabetic heart failure and kidney disease, where trials have shown benefits. Potential additional uses discussed include NAFLD, obesity, sleep apnea, and PCOS, though evidence is limited. Risks are discussed for using SGLT2 inhibitors in type 1 diabetes or with very low carb diets. In conclusion, SGLT2 inhibitors have cardio-renal-metabolic effects but significant challenges remain in establishing their role for various non-standard conditions.
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SGLT2 inhibitors - what's new?
- 1. SGLT2 inhibitors - Whatâs new? Karthik Balachandran ďkarthik2k2 November 16, 2020 Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 1 / 45
- 3. Disclaimer DapagliďŹozinâs patent case is subjudice. We shall wait for the decision of the judiciary. Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 3 / 45
- 4. Basics
- 5. The menu ⌠Available in India ⢠EmpagliďŹozin ⢠CanagliďŹozin ⢠DapagliďŹozin ⢠RemogliďŹozin Not available in India ⢠IpragliďŹozin ⢠LuseogliďŹozin ⢠TofugliďŹozin ⢠SotagliďŹozin ⢠ErtugliďŹozin Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 5 / 45
- 6. SGLT2 inhibitors - Glucoretics Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 6 / 45
- 7. More than a glucoretic ⌠Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 7 / 45 Diabetologia 61,2098â2107(2018)
- 8. Guideline Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 8 / 45
- 9. Tradeoffs ⌠Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 9 / 45
- 10. Uses Standard Indication Type 2 diabetes mellitus Diabetes with heart failure Diabetes with chronic kidney disease Special subgroups Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 10 / 45
- 11. CVOTS in a nutshell Trial MACE HF CKD EMPA-REG â â â CANVAS â â â DECLARE-TIMI Ă â â Heart failure and CKD beneďŹts are class effects Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 11 / 45
- 12. Uses Non standard uses ⢠Non diabetic heart failure ⢠Non diabetic kidney disease ⢠Type 1 diabetes ⢠Obesity ⢠NAFLD ⢠Obstructive sleep apnea ⢠SIADH ⢠PCOS ⢠LCHF â Keto diet augmentation Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 12 / 45
- 13. Whatâs the evidence? Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 13 / 45
- 14. Non diabetic heart failure ⢠DAPA-HF ⢠EMPEROR-Reduced Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 14 / 45
- 15. How do SGLT2 inhibitors help in non diabetic heart failure? Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 15 / 45 Packer European Heart Journal (2020) 41, 2393â2396
- 16. DAPA-HF DapagliďŹozin arm had lower risk of cardiovascular death or hospitalization for heart failure, regardless of the presence or absence of diabetes Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 16 / 45
- 17. EMPEROR-Reduced EmpagliďŹozin arm had lower risk of cardiovascular death or hospitalization for heart failure, regardless of the presence or absence of diabetes Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 17 / 45
- 18. #AllOrgansMatter Heart Liver Kidney Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 18 / 45
- 19. #AllOrgansMatter Heart Liver Kidney Heart Liver Kidney Organ risk The size of the un-shaded region matters Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 18 / 45
- 20. Kidney and SGLT2 inhibitors Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 19 / 45
- 21. Metabolic Swiss army knife Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 20 / 45
- 22. ROTs ? Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 21 / 45
- 23. DAPA-CKD Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 22 / 45
- 24. SGLT2 inhibitors and liver - why? Normal NAFLD NASH Cirrhosis
- 25. SGLT2 inhibitors and liver - why? Normal NAFLD NASH Cirrhosis 25% 25% 20% Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 23 / 45
- 26. SGLT2 inhibitors and the liver - why? Reduce liver fat without weight gain Should be preferably oral Should be beneďŹcial for the heart & kidney Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 24 / 45
- 27. SGLT2 inhibitors and liver - how? Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 25 / 45
- 28. SGLT2 and liver - evidence Why not LOTs? ⢠Diagnosis and staging requires liver biopsy ⢠No âdiscreteâ liver events Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 26 / 45
- 29. SGLT2 and liver -evidence SGLT-2 inhibitors improve the serum level of liver enzymes, decrease liver fat, and ďŹbrosis with additional beneďŹcial effects on various metabolic parameters in type 2 diabetes patients with NAFLD Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 27 / 45
- 30. SGLT2 inhibitors and liver - where? Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 28 / 45
- 31. SGLT2 inhibitors and liver - where? 1 SGLT2 inhibitor + Pioglitazone - counteracts the ďŹuid retention and weight gain induced by Pioglitazone Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 29 / 45
- 32. SGLT2 inhibitors and liver - where? 1 SGLT2 inhibitor + Pioglitazone - counteracts the ďŹuid retention and weight gain induced by Pioglitazone 2 SGLT2 inhibitor + GLP1RA - different mechanisms of action, potential additional weight loss Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 29 / 45
- 33. SGLT2 inhibitors and OSA Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 30 / 45
- 34. SGLT2 inhibitors and OSA Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 31 / 45
- 35. SGLT2 inhibitors and SIADH Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 32 / 45
- 36. SGLT2 inhibitors and SIADH Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 33 / 45
- 37. SGLT2 inhibitors and obesity ⢠Given that SGLT2 inhibitors cause â 75 gm glucose loss per day, the expected weight loss over 24 weeks would be â 7 kg ! ⢠But they are far less effective :-( ⢠Compensatory hyperphagia occurs ⢠Combination with appetite suppressants? 1 1 The appetite suppressant must be safe Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 34 / 45
- 38. DURATION8 trial Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 35 / 45
- 39. AWARD10 trial Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 36 / 45
- 40. SGLT2 inhibitors and PCOS Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 37 / 45
- 41. SGLT2 inhibitors and PCOS SGLT2 inhibitors improved athropometric parameters and body composition, but not metabolic parameters or hormones in 20 overweight - obese PCOS women treated for 12 weeks Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 37 / 45
- 42. SGLT2 inhibitors in Type 1 diabetes Starting SGLT2 inhibitors in patients with type 1 diabetes is risky. Extreme caution advised Achtung! ⢠Euglycemic DKA canât be detected by blood glucose monitoring ⢠Glucose centric monitoring â Ketone centric monitoring Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 38 / 45
- 43. Therapeutic augmentation of LCHF diet Starting LCHF diet in diabetes patients on SGLT2 inhibitors is dangerous and must not be done without medical supervision Achtung! ⢠In patients with refractory epilepsy it has been attempted 2 ⢠Potential use in adults with obesity? 2 Blunck JR et al. Therapeutic augmentation of ketogenic diet with a sodium-glucose cotransporter 2 inhibitor in a super-refractory status epilepticus patient. Epilepsy Behav Case Rep. 2018;10:61-64. Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 39 / 45
- 45. Silos Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 41 / 45 Circ Cardiovasc Qual Outcomes. 2020;13:e007264
- 46. The Gut â Kidney pivot 2005-2015 2015- Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 42 / 45
- 47. Summary Potential uses & Evidence ⢠Non diabetic heart failure ď ⢠Non diabetic kidney disease ď ⢠NAFLD ď ⢠Obesity ď ⢠Obstructive sleep apnea ď ⢠PCOS ď ⢠SIADH ď ⢠LCHF â Keto diet augmentation ď ⢠Type 1 diabetes ď Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 43 / 45
- 48. Conclusions ⢠SGLT2 inhibitors are cardio-renal-metabolic drugs, with pleiotropic actions ⢠Emerging evidence is positive, signiďŹcant challenges exist in making it âeveryoneâsâ solution Karthik SGLT2 inhibitors - Whatâs new? November 16, 2020 44 / 45
- 49. Thank you ! This presentation can be downloaded from www.medicalruminations.wordpress.com cbna