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CORE PRINCIPLES OF TREATMENT OF DIABETES MELLITUS.pptx
The document presented by Dr. Deepak Anand discusses the management and treatment of diabetes mellitus, highlighting diagnostic work-up, trends in diabetes prevalence, and the importance of glycemic control to prevent complications. It outlines various medication classes used in diabetes treatment, including both oral and injectable agents, as well as newer therapeutic approaches on the horizon. The document also touches upon promising research areas such as fecal microbiota transplantation and gene therapy for diabetes.
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CORE PRINCIPLES OF TREATMENT OF DIABETES MELLITUS.pptx
- 1. VERTICAL INTEGRATION Dr DeepakAnand R MBBS, DNB (Med), MRCP, IDCCM Associate Professor Department of General Medicine
- 2. Manageme nt of Diabetes Mellitus Feeling blessed…Thanks to Department of Pharmacology…
- 3. Management Work up &Treatment
- 4. Work Up Work Upfor Diagnosis/Monitoring • Fasting Blood Sugar • Postprandial Blood Sugar • HbA1C • Urine Routine Work up for Complications • Biothesiometry • Fundus Examination • Urine Micralbumin • Urea & Creatinine
- 5. How many ofyou have watched this movie ???
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- 9. Worrying Trend… 2019 2045 0 20 40 60 80 100 120 140 160 ChartTitle CHINA INDIA USA PAKISTAN BRAZIL MEXICO INDONESIA EGYPT BANGLADESH Kanwal A, Kanwar N, Bharati S, Srivastava P, Singh SP, Amar S. Exploring New Drug Targets for Type 2 Diabetes: Success, Challenges and Opportunities. Biomedicines. 2022 Jan 31;10(2):331. doi: 10.3390/biomedicines10020331. PMID: 35203540; PMCID: PMC8869656
- 10. The Trend inmore detail… CHINA INDIA USA PAKISTAN BRAZIL MEXICO INDONESIA MEXICO BANGLADESH 0 20 40 60 80 100 120 140 160 Projected Prevalence of Diabetes 2019 2045
- 11. The Silver Lining… CHINAINDIA USA PAKISTAN BRAZIL MEXICO INDONESIA MEXICO BANGLADESH 0 20 40 60 80 100 120 140 160 Projected Prevalence of Diabetes 2019 2045 Remember, we have overtaken China in population this year
- 12. Why do weneed to treat Diabetes Mellitus ??? What are we trying to prevent or Achieve ???
- 15. Complications Macrovascula r Coronary Artery Disease Cerebrovascula r Disease Peripheral ArterialDisease Microvascular Neuropathy Retinopathy Nephropathy aka ATHEROSCLEROS IS aka TRIPATHY
- 16. Do we needto blood sugar levels to normal levels if at all they get deranged ??? Yes or No ???
- 17. Treatment Matters • The UniversityGroup Diabetes Program (UGDP) – 1960s • placebo, tolbutamide, phenformin, or insulin • Increase in Cardiovascular deaths • Stopped after 8 years
- 18. Landmark Trials inDM UKPDS ADVANC E VADT ACCORD
- 19. Treatment Matters • UKPDS –1970s • Largest and longest of it’s kind • Conclusively proven benefits of good glycemic control • Median follow up was 10 yrs
- 20. Treatment Matters • DCCT TRIAL: • Demonstrated the LEGACY EFFECT OR METABOLIC MEMORY • Study Duration : 6.5 yrs
- 21. Quick Recap onTypes of Diabetes DM Specific Types Type 2 GDM Type 1
- 22. Ten Classes –roughly Sixty Medications More than 100 are in TRIALS • 1) sulfonylureas • 2) meglitinides • 3) metformin (a biguanide) • 4) thiazolidinediones (TZDs) • 5) alpha glucosidase inhibitors • 6) dipeptidyl peptidase IV (DPP-4) inhibitors • 7) bile acid sequestrants • 8) dopamine agonists • 9) sodium-glucose transport protein 2 (SGLT2) inhibitors • 10) oral and injectable glucagon like peptide 1 (GLP-1) receptor agonists Also, we have Injectables like Amylin Analogues
- 23. TRIUMVIRATE TO OMINOUSOCTET Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009 Apr;58(4):773-95. doi: 10.2337/db09-9028. PMID:
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- 25. Sweetening Sixteen • Beyond OminousOctet & Egrigious Eleven Phatak, Sanjeev R.; Saboo, Banshi; Dwivedi, Shivangi; Zinzuwadia, Padmanabh; Panchal, Dharmendra; Ganguli, Abhilasha; Hasnani, Dhruvi Journal of Diabetology12(1):1-9, Jan-Mar 2021. doi: 10.4103/jod.jod_9_20
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- 30. Injectable Anti Diabetics Insulin Human Analogues GLP 1R Agonists Infusion Once Daily Weekly Amylin Analogue Pramlintide Injections
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- 34. BIGUANIDES • Metformin • SheetAnchor in the management of Diabetes • Also approved for use in pregnancy • GI side effects – problematic • Cannot be used in renal failure
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- 36. Alpha Glucosidase Inhibitors •Voglibose & Acarbose • Very very relevant for Indian Diabetics • Only control post prandial spikes • Can only be an add on • Can be used in IGT to delay Diabetes onset • GI intolerance is the Achilles Heel
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- 40. PPAR GAMMA AGONISTS •Pioglitazone • Lobeglitazone • Former is controversial • Weight Gain, Edema & Fractures are problematic
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- 44. INCRETIN MIMETICS DPP4i • GLIPTINS •Lina • Sita • Vilda • Teneli • Evo • Gemi GLP1 R A • GLUTIDES • Lira • Dula • Sema
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- 46. SGLT2i • The Gliflozins •Are Cardioprotective • Can be used in Heart Failure without Diabetes • GTI/UTI is their Achilles Heel • Dapa, Empa, Cana, Remo
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- 48. Lobeglitazone • The Dusthas settled on Pioglitazone • Available in Indian Market • 0.5 mg per day • Monotherapy as well as FDC with Metformin • It’s a PPAR Gamma Agonist
- 49. Imeglimin • first inclass novel oral agent ‐ ‐ • tetrahydrotriazine containing molecule, the class will be called glimins ‐ • Mechanism of Action : • (a) amplification of glucose‐stimulated insulin secretion (GSIS) and preservation of β‐cell mass; • (b) enhanced insulin action, including the potential for inhibition of hepatic glucose output and improvement in insulin signaling in both liver and skeletal muscle • Aka “correction of mitochondrial dysfunction” • Available in Indian Market
- 50. Newer Drugs in theHorizon for Diabetes Mellitus
- 51. Icodec • The ONWARDS3 Randomized Clinical Trial • No difference in weight change • a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient- year exposure in both groups
- 52. Cagrilintide • Stable, lipidatedlong-acting amylin analogue cagrilintide • Amylin is a 37 amino acid peptide, produced in pancreatic beta cells and co-secreted with insulin • It has important effects on appetite, glucose management, and gastric emptying that warrant investigation for treatment of diabetes and obesity • Human amylin is also involved in the cytotoxic amyloid formation
- 53. FDC of BASALINSULIN - GLP1RA • IDegLira • Sanofi • Degludec + Liraglutide • Once Daily • DUAL II, DUAL V & DUAL VII trials • Phase 3 • Lower chances of Hypoglycemia than Basal-Bolus
- 54. Novo Nordisk CAGRISEMA • FDCof 2.4 mg semaglutide and 2.4 mg cagrilintide • Viz. GLP1RA & Amylin Analogues • Both promote weight loss • Weekly once • Subcutaneous Injection • Completed Phase 2 in August 2022, entering Phase 3
- 55. FDC OF BASALINSULIN - GLP1RA • IcoSema • Icodec + Semaglutide • Once Weekly • Novo Nordisk
- 56. RETATRUTIDE Retatrutide Tirzepatid e Eli Lilly, Phase2 GLP1+GIP+GLUCAGON GLP1+GIP GLP1
- 57. PRAMLINTIDE The only anti-diabetic otherthan insulin approved for use in T1DM Didn’t gain much fanfare…
- 58. Eating less &Staying Thin may not be by CHANCE or CHOICE but by TRAIT ROLE OF FECAL MICROBIOTA TRANSPLANT IN DIABETES MELLITUS Chen L, Guo L, Feng S, et al Fecal microbiota transplantation ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota in db/db mice BMJ Open Diabetes Research and Care 2023;11:e003282. doi: 10.1136/bmjdrc-2022-003282
- 59. COPROPHAGY IN ANCIENTGREEK FMT – FECAL MICROBIOTA TRANSPLANT • MICROBIOTA or GUT MICROBIOME • The term ‘microbiome’ refers to the collective genomes of these microorganisms. • 1100 prevalent species • Minimum 160 per individual • 10 to 100 trillion individual cells • Difficult (read impossible) to isolate and culture • Study the 16 S rRNA and metagenomics instead
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- 61. ORMD – 0801(aka) ORAL INSULIN • Presently in Phase 3 • 8 mg HS appears to be the most promising dose • Safe, well tolerated and not associated with weight gain or hypoglycemia Eldor R, Neutel J, Homer K, Kidron M. Efficacy and safety of 28-day treatment with oral insulin (ORMD-0801) in patients with type 2 diabetes: A randomized, placebo-controlled trial. Diabetes Obes Metab. 2021 Nov;23(11):2529-2538. doi: 10.1111/dom.14499. Epub 2021 Aug 18. PMID: 34310011. Eldor R, Francis BH, Fleming A, Neutel J, Homer K, Kidron M, Rosenstock J. Oral insulin (ORMD-0801) in type 2 diabetes mellitus: A dose-finding 12-week randomized placebo-controlled study. Diabetes Obes Metab. 2023 Apr;25(4):943-952. doi: 10.1111/dom.14901. Epub 2022 Nov 21. PMID: 36281496.
- 62. Cure for EarlyType 1 Diabetes • All is not lost ideology • Teplizumab – Anti-CD3 Antibody • Must be used sufficiently early in the course of Type 1 Diabetes Mellitus • Can delay the onset in anti-body positive individuals
- 63. Transdifferentiation • Case forcells : α • and cell lineages appear to arise from α β a common precursor • Phenomenon already known in mice models • Both cells have common Slc2a2 transporter that allows glucose sensing • Anatomically same Blood and Nerve supply • 35 % of cells in Islets are cells α • Reduction in number of cells doesn’t α translate to adverse outcomes
- 64. TRANSDIFFERENTIATION BYGENE THERAPY The transcriptionfactors are delivered using Adenovirus vectors into the Pancreatic duct Animal Studies
- 65. Xu L, GuoY, Huang Y, Xu Y, Lu Y, Wang Z. Hydrogel materials for the application of islet transplantation. Jo Islet Cell Transplant • Islet encapsulation is an active area of research aimed at shielding implanted islets from immunological rejection and inflammation while still allowing for effective insulin and nutrient exchange with donor cells. • “Hydrogels” have been a major subject of focus in the field of islet transplantation and encapsulation technology • Made of Alginate-Graphene Oxide
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- 67. Thank You Dr DeepakAnand R MBBS, DNB (GM), MRCP (UK), IDCCM Associate Professor General Medicine
Editor's Notes
- #55 As you can see, it’s my personal favourite…