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![Newer Insulin delivery systems & glucose
monitors
• Insulin Pumps
• CSII ( continues subcutaneous insulin infusion)
• Dexcom G5 Mobile Continuous Glucose Monitoring System,
Approved December 20, 2016 [Sensor, transmitter, compatible
smart phone, or a smart watch]
• Freestyle Libre Flash Glucose Monitoring System, Approved
September 27, 2017 [sensor plus mobile reader]
• In Pen system (smart insulin pen]: FDA approved in 2017 for apple iOS
and for android version in 2018
• Is the first reusable insulin injector pen](https://image.slidesharecdn.com/treatmentofdiabetesmellitus-230713185821-ec4323a5/75/treatment-of-diabetes-mellitus-pptx-14-2048.jpg)
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Similar to treatment of diabetes mellitus.pptx
treatment of diabetes mellitus.pptx
- 1. Newer treatment fordiabetes Mellitus and latest protocol Dr Indra Saini Guide Dr Narendra Rawat Sir
- 2. • Diabetes mellitusis the group of common metabolic disorders that share the phenotype of hyperglycemia. • Depending upon the etiological factors contributing to hyperglycemia include reduced insulin secretion, increase insulin resistance, decrease glucose utilization, and increase glucose production. • DM is the leading cause of end stage renal disease , increase risk of cardiovascular mortality and morbidity.
- 3. Comprehensive medical carefor diabetes mellitus • Glycemic goal and therapeutic plan • Monitoring of blood glucose level –by SMBG and CGM • HbA1c testing (2-4 time/year) • Life style management • Detection ,prevention and management of diabetes related complications • Manage diabetes related condition- hypertension lipids consider antiplatelet drugs
- 4. Life style Managementin Diabetes care • 1. Diabetes Self Management Education and Support (DSMES)- refer to way to improve the patient knowledge, skills, abilities necessary for diabetes self care and should also emphasizes on psychological issue and emotional well being. • 2. Nutrition therapy- Medical nutrition therapy (MNT) • Used by ADA to describe the optimal coordination of calorie intake with other therapy of diabetes (insulin, exercise, weight loss) • MNT in type 1 DM - to minimize weight loss often due to insulin therapy by placing limit on carbohydrate intake. • IN type 2 DM MNT- focus on weight loss and address the greatly increase prevalence of CV risk factor • Emphasize on Modest calorie reduction ,increase physical activity and weight loss
- 5. • 3. Physicalactivity- • Patient with DM ADA recommends 150 min/week(distributed over at least 3 day) of moderate aerobic physical activity with no gaps longer than 2 days • 4. Psychological care – • Psychological assessment and support are critical part of comprehensive diabetes care
- 6. Monitoring the levelof glycemic control • Short term glycemic control- 1. Self monitoring of blood glucose- the frequency of SMBG should be individualized in type 1 and type 2 DM 2. Continuous glucose monitoring- CGM technology utilise a sensor or electrode to detect interstitial glucose which is equilibrium with blood glucose • The sensor placed subcutaneously and replaced every 3-14 days • CGM provide – TIME IN GLYCEMIC RANGE(TIR), ambulatory glucose profile, amount of time in hypoglycaemic range and glucose management indicator(GMI)
- 7. • CGM intype 1 DM decrease the frequency of hypoglycemia • The combination of CGM and insulin infusion device now automate insulin delivery with predictive suspension of insulin delivery to avoid hypoglycemia. • Long term glycemic control-measurement of HbA1c level that reflect glycemic control over past 2-3 months • The fructosamine assay measuring glycated albumin reflect the glycemic status over the prior 2 week
- 8. Treatment of type1 DM mellitus In type 1 DM lack of endogenous insulin production, admiration of basal insulin is essential for regulating glycogen breakdown , gluconeogenesis, lipolysis and ketogenesis Intensive insulin therapy has the goal of achieving near normal glycemia Insulin regimen include- 1. Multiple component insulin regimen 2. Multiple daily injection (MDI) 3. Continuous subcutaneous insulin infusion (CSII)
- 9. Insulin preparations TYPE ONSET (Hr) PEAK (Hr) DOA (Hr) Shortacting Ultra short acting Regular insulin Aspart Glulisine lispro 0.5-1 <0.25 <0.25 <0.25 2-4 0.5-1.5 4-8 3-5 Intermediate acting Isophane(NPH) Lente 1-2 8-10 10-16 Long acting Glargine Detemir Degludec 2-4 1-4 1-9 - 20-24 12-24 42
- 10. Insulin degludec • Ultralong acting insulin analogue, Threonine in B30 replaced by Myristic acid • It Self aggregation in subcutaneous tissue and bound to albumin in circulation and prolong its duration of action . Advantage - • Hypoglycaemia less frequent than NPH • Lesser Nocturnal hypoglycaemia • Lesser or minimal weight gain • Effective at physiological ph.
- 11. Insulin detemir long actingbasal insulin • Bind to albumin and prolong its duration of action • Onset 1-4 hr • Duration of action 12-20 hr • Twice daily injection required for 24 hr basal coverage
- 12. Insulin glargine • Longacting analogue of human insulin • Aspargine replaced by glycine at 21 in b chain • Microscopic precipitate at physiological PH in subcutaneous tissue • Duration of action 24 hr • Peak less insulin • Cannot be mixed with other insulin
- 13. Inhaled insulin TYPES • Afrezza–FDA approved in 2004 Rapid acting human insulin • Similar to ultra short acting insulin ,should be used with long acting insulin in type 1 DM • Bioavailability- 9 to 22% Contradiction- • Smokers • Poorly controlled lung disease- Asthma ,COPD • Allergic patient
- 14. Newer Insulin deliverysystems & glucose monitors • Insulin Pumps • CSII ( continues subcutaneous insulin infusion) • Dexcom G5 Mobile Continuous Glucose Monitoring System, Approved December 20, 2016 [Sensor, transmitter, compatible smart phone, or a smart watch] • Freestyle Libre Flash Glucose Monitoring System, Approved September 27, 2017 [sensor plus mobile reader] • In Pen system (smart insulin pen]: FDA approved in 2017 for apple iOS and for android version in 2018 • Is the first reusable insulin injector pen
- 15. Combination therapy intype 1 DM • Add GLP-1 Receptor agonist along with basal insulin • Potent glucose lowering action, less weight gain, hypoglycemia • Two fixed dual combination products containing basal insulin and GLP-1 RA are available Insulin glargine with lixisenatide Insulin degludec with liraglutide
- 16. INSUIN REGIMEN • Inall regimens long acting insulin supply basal insulin, where short acting insulin supply prandial insulin injected just before ( <10 min )meal • In general individual with type 1 DM require 0.3-0.7unit/kg per day • Dived into 50% of daily insulin given as basal insulin and 50% as prandial insulin • CS II – very effective insulin regimen for the patient with type 1 DM To the basal insulin infusion , a pre -prandial insulin ( bolus) is delivered by insulin infusion device • Hybrid closed loop system –recently become available that combine with pre-prandial bolus and automated adjustment of insulin based on CGM
- 17. Newer drug approval 1.Tzield(teplizumab-mzwv) Injection • Company: Provention Bio • Date of Approval: November 17, 2022 • Tzield (teplizumab-mzwv) is a CD3-directed antibody Treatment for: Delaying the Onset of Stage 3 Type 1Diabetes 2. Lyumjev (insulin lispro-aabc injection) INDIANAPOLIS, June 15, 2020 /PRNewswire - The U.S. Food and Drug Administration (FDA) has approved Eli Lilly and Company's (NYSE: LLY) Lyumjev (insulin lispro-aabc injection, 100 units/mL and 200 units/mL New rapid-acting insulin indicated for type 1 diabetes and type 2 diabetes. Contradiction- during episode of hypoglycaemia, hypersensitivity reaction
- 18. 3.FDA Approves Semglee •(insulin glargine-yfgn) as the First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes Indicated to improve glycemic control in adults and pediatric patients with Type 1 and Type 2 diabetes mellitus. SILVER SPRING, Md., July 28, 2021 /PRNewswire/ -- Today,
- 19. Treatment for type2 DM 1. Glycemic control – • Life style/diet • Exercise • Medication 2. Treat associated condition- • Dyslipidemia • Hypertension, obesity 3. Management of complications
- 20. 0ral Hypoglycemic Drug DRUGMOA ADVANTAGE DISADVANTAGE CONTRAINDICATION BIGUNAUIDES metformin Hepatic glucose production ,increase insulin sensitivity Weight neutral, no hypoglycemia, inexpensive Diarrhoea,nausea ,lactic acidosis, vitamin B12 deficiency Renal insufficiency(GFR<30 ml/min) hospitalized patient, unstable CHF, acidosis SULFONYLUREA K +ATP channel blocker, increase insulin secretion Lower post prandial glucose, inexpensive Hypoglycemia ,weight gain Renal /liver insufficiency MEGLITINIDE Insulin secretion increase Faster onset, lower post prandial glucose Hypoglycemia Renal /liver insufficiency ALPHA GLUCOSIDASE INHIBITOR decrease GI absorption of glucose Reduce post prandial glucose GI flautuence,raise liver enzyme Renal /liver insufficiency
- 21. , THIAZOLIDINEDIONES Insulin resistance Glucoseutilization increase Lower insulin requirement Peripheral edema, CHF,weight gain,fracture, macular edema CHF, Renal/liver insufficiency DPP-4 INHIBITORS GLP-1 action Insulin ,glucagon No hypoglycemia Immune mediated dermatological side effect Reduced dose with renal insufficiency
- 22. GLP-Receptor agonists • Mechanismof action- • Incretin effect- augment glucose dependent insulin secretion suppression of glucagon decrease gastric emptying • Clincal efficacy- high to very high no risk of hypoglycemia weight loss • Cardiorenal effect- benefit effect on CVD benefit effect on diabetic kidney disease
- 24. • Benefit onCVD include- • dulaglutide, liraglutide, semaglutide • Neutral effect on CVD- exenatide given once weekly • lixisenatide • Effect on DKD- dulaglutide, liraglutide,semaglutide Shorter acting – daily injection required Exenatide – twice daily injection required no effect in CVD events Liraglutide Lixisenatide longer acting- given weekly Sustanied release exenatide Dulaglutide Semaglutide (oral)
- 25. • Adverse effect– GI side effect- Nausea, vomiting ,diarrhea increase risk of acute pancreatitis • Contradiction – in patient with increase risk of medullary carcinoma of thyroid
- 26. Glucose-dependent insulinotropic polypeptide (GIP)receptor and GLP-1 receptor agonist (tirzepatide) Mechanism of action: GIP receptor and GLP-1 receptor agonist; enhances first and second-phase insulin secretion, and reduces glucagon levels, both in a glucose-dependent manner • Clinical Efficacy profile: Very high glycemic efficacy; • low inherent risk of hypoglycaemia; • weight loss (high); • Cardiorenal effects unknown (trials in progress)
- 27. DPP-4 INHIBITOR • Mechanismof action- increase the effect of incretin by inhibiting DPP- 4 ENZYME • Intermediate glucose-lowering efficacy • Neutral effect on weight, generally well tolerated • Minimal risk of hypoglycemia • RENAL Adjustment required- sitagliptin, sexagliptin, alogliptin • No dose adjustment required for linagliptin • Usually neutral effect in CVD, HF,DKD
- 28. Mechanism of action:Reduce renal tubular glucose reabsorption glucose lowering effect independent of Insulin they reduce the reabsorbtion of Na so mild diuretic effect and reduction of SBP • Clinical Efficacy Profile: Intermediate to high glucose-lowering efficacy lower at lower eGFR; NO risk of hypoglycemia; Intermediate weight loss • Cardiorenal Effects: Demonstrated protective effects in studied trial populations: • Reduction in major adverse cardiovascular events • Reduction in overall CV death (with heterogeneity across the class) • Reduction in risk of hospitalisation for heart failure • Reduction in risk of kidney outcomes SGLT2 Inhibitors
- 29. • Effect onCVD , HF, DKD – all SGLT -2 inhibitors reduced hospitalization for HF, reduce progression of diabetic kidney disease • Canagliflozin • Empagliflozin • Dafagliflozin • glucose lowering effect is lower if eGFR lower ( eGFR<45 /min) • Disadvantage – • Increase risk of UTI, ketoacidosis in DM 1 • Contradiction – type 1 and pancreatic form of diabetes
- 30. N Engl JMed 2019; 381:1995-2008 Patient Population: With heart failure and a reduced ejection fraction, regardless of the presence or absence of diabetes. n = 4744 Dose: Dapagliflozin 10 mg daily *≥400 pg/ml if HF hospitalization within ≤12 months; ≥900 pg/ml if atrial fibrillation/flutter 30 The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial (DAPA-HF)
- 31. N Engl JMed 2019; 381:1995-2008 The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial (DAPA-HF) -26% -30% -18% -17% The primary composite outcome of CV death & hospitalization for heart failure reduced by 26%. • First episode of worsening HF was reduced by 30% • The risk of CV death was reduced by 18% In patients with HF with reduced Ejection Fraction, the risk of worsening HF or death from CV causes was lower among those who received Dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes 31
- 32. Empagliflozin Causes Regressionof Albuminuria in Patients with Prior Micro- or Macro-albuminuria (EMPA-REG OUTCOME) Patients with Prior Microalbuminuria Regression to Normoalbuminuria Patients with Prior Macroalbuminuria Regression to Normo / Microalbuminuria 43% ↑ Likelihood with Empagliflozin 82% ↑ Likelihood with Empagliflozin Cherney DZI et al. Lancet Diabetes Endocrinol. 2017 Aug;5(8):610-21. UACR: Urine Albumin-Creatinine Ratio. Normoalbuminuria: UACR <30 mg/g. Microalbuminuria: UACR ≥30 to ≤300 mg/g. Macroalbuminuria: UACR >300 mg/g.
- 33. Guideline Recommendations In patientswith type 2 diabetes who have established atherosclerotic cardiovascular disease or indicators of high risk, established kidney disease, or heart failure ADA Recommends Early Combination Therapy with SGLT2i & DPP4i is recommended as part of the glucose-lowering regimen independent of A1C and in consideration of patient-specific factors .1 1. Diabetes Care Volume 44, Supplement 1, January 2021 33
- 34. Davies MJ, ArodaVR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB Diabetes Care 2022; https://doi.org/10.2337/dci22-0034. Diabetologia 2022; https://doi.org/10.1007/s00125-022-05787-2.
- 35. Choosing glucose-lowering medicationin people with CVD ASCVD = atherosclerotic cardiovascular disease Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB Diabetes Care 2022; https://doi.org/10.2337/dci22-0034. Diabetologia 2022; https://doi.org/10.1007/s00125-022-05787-2. •In people with established CVD, a GLP-1RA with proven benefit should be used to reduce MACE or an SGLT2i with proven benefit should be used to reduce MACE and HF and improve kidney outcomes.
- 36. Choosing glucose-lowering medicationin people with chronic kidney disease Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB Diabetes Care 2022; https://doi.org/10.2337/dci22-0034. Diabetologia 2022; https://doi.org/10.1007/s00125-022-05787-2. •In people with CKD, SGLT-2 inhibitors and GLP-1RA reduce risk of MACE independent of eGFR. •In people with CKD, SGLT2i also reduce risks of HF and kidney outcomes (including end-stage kidney disease
- 37. Choosing glucose-lowering medicationin people with heart failure In people with heart failure SGLT2i should be used because they improve heart failure and kidney outcomes. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB Diabetes Care 2022; https://doi.org/10.2337/dci22-0034. Diabetologia 2022; https://doi.org/10.1007/s00125-022-05787-2.
- 38. Insulin therapy intype 2 DM Insulin therapy indicated in patient with – • Lean individual or with severe weight loss • Underlying renal and hepatic disease • Acute severe hyperglycemia • If Hba1c% >9% • Initiate with single dose of long acting insulin (0.1-0.4U /kg)per day at bed time may be adjusted in 10-20% increment as detected by SMBG result.
- 39. ADA Standards ofCare - 2022 Guidance
- 40. Other therapy fordiabetes mellitus • Metabolic – • bariatric surgery- should be considered in individual in BMI>30Kg/m2 if hyperglycemia inadequately controlled despite optimal medical therapy • Short term caloric restriction-(very low calorie diet, typically (800- 1000 calorie/day) • Pancreatic transplantation –whole pancreases or pancreatic islet transplantation indicated in patient with severe metabolic instability or patient already require immunosuppression for kidney or other organ transplantation.
- 41. Bile Acid-Binding Resins •Colesvelam: • Approved for the treatment of type 2 diabetes.. • Mechanism of Action. • Bile acid metabolism is abnormal in patients with type 2 diabetes , act as signaling molecules through nuclear receptors, some of which may act as glucose sensors. • Adverse effect : • dyspepsia, abdominal pain, and nausea affecting up to 10% of treated patients. increase plasma triglycerides Pregnancy category B drug Therapeutic Uses. Treatment of hypercholesterolemia and may be used for treatment of type 2 diabetes
- 42. Emerging therapies • 1.Activatorof glucokinase • Glucokinase is an enzyme present in pancreases alpha and beta cell • Glukinase activation act as prominent regulator of hepatic intermediary and energy metabolic pathway • Trial of two drugs MK0941 and piragliptin were terminated previously. • Inhibitor of 11 beta hydroxysteroid dehydrogenase • GPR-40 agonists • targeting glucose dependent insulinotropic polypeptide receptor and GLP-1 receptor. A novel GPR40 agonist TAK-875 shown to significantly improvement in glycemic control. • Combined SGLT-1 AND SGLT-2 Inhibitors • Anti CD-3 monoclonal antibody-otelixizumab,teplizumuab
- 43. Imeglimin (twymeeg)- • Oralantidiabetic • Approved in Japan in 2021 • Mode of action – 1.direct effect on islet –beta cell to enhance glucose stimulated insulin secretion (GSIS) • Prevent loss of beta cell mass 2. Enhance insulin action in both liver skeletal muscle Use – type 2 DM as an Add on therapy with metformin or sitagliptin
- 44.