Oralanti diabetic hyperglycemic drugs.pptx

different medication of oral hypoglycemic drugs used in Diabetic patients

1. Type 2 Diabetes medication Sakarie Ahmed Saed

2. Biguanides Insulin secretagogues : Sulfonylureas Insulin secretagogues : Non sulfonylureas ᾳ- glucosidase inhibitor Dipeptidyl peptidase(DPP) inhibitors SGLT-2 inhibitors Thiazolidinediones

3. Endocrine Practice  2023 29305-340DOI: (10.1016/j.eprac.2023.02.001) Copyright © 2023 AACE Terms and Conditions

4. Date of Download: 4/20/2024 Copyright © 2024 American Diabetes Association. All rights reserved. From: 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2023 Diabetes Care. 2022;46(Supplement_1):S140-S157. doi:10.2337/dc23-S009 Use of glucose-lowering medications in the management of type 2 diabetes. ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin-to-creatinine ratio; ARB, angiotensin receptor blocker; ASCVD, atherosclerotic cardiovascular disease; CGM, continuous glucose monitoring; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; CVOT, cardiovascular outcomes trial; DPP-4i, dipeptidyl peptidase 4 inhibitor; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; MACE, major adverse cardiovascular events; MI, myocardial infarction; SDOH, social determinants of health; SGLT2i, sodium-glucose cotransporter 2 inhibitor; T2D, type 2 diabetes; TZD, thiazolidinedione. Adapted from Davies et al. (45). Figure Legend:

5. Biguanides ( Metformin ) Mechanism of action :↓Hepatic glucose production, ↑insulin sensitivity, influence gut function Examples : Metformin ↓ A1c by1–2% Advantages: Weight neutral, do not cause hypoglycemia , inexpensive, extensive experience, ↓CV events Disadvantages: Diarrhea, nausea, lactic acidosis, vitamin B12 deficiency contraindications Renal insufficiency (see text for GFR <30 mL /min), CHF, radiographic contrast studies, hospitalized patients, acidosis

6. Dosing: Adult ( Metformin ) Immediate release: Initial:  Oral:  500 mg once or twice daily  or  850 mg once daily Dosage adjustments:   Oral:  The dose should be increased gradually to minimize GI adverse effects. Titration strategies vary widely, but usually done in 500 mg or 850 mg increments every 7 days (range: 5 days to 1 month). Usual maintenance dosage:   Oral:  1 g twice daily  or  850 mg twice daily Maximum:   Oral:  2.55 g/day

7. Extended release: Initial:   Oral:  500 mg to 1 g once daily Dosage adjustments:   Oral:  The dose should be increased gradually to minimize GI adverse effects. Titration strategies vary widely, but usually done in 500 mg increments every 7 days (range: 7 days to 6 weeks). Maximum:   Oral:  2 g/day.

8. Altered kidney function: eGFR ≥60 mL /minute/1.73 m 2 : No dosage adjustment necessary. Monitor renal function at least annually. eGFR >45 to <60 mL /minute/1.73 m 2 : No dosage adjustment necessary. monitoring of renal function every 3 to 6 months

9. eGFR 30 to 45 mL /minute/1.73 m 2 : Initiation of therapy:  Use generally not recommended ; however, initial therapy with 500 mg once daily with the evening meal titrated to 500 mg twice daily, if tolerated, with close monitoring of kidney function has been recommended by some experts . Continuation of existing therapy:  May continue at a reduced dose up to a maximum of 500 mg twice daily with close monitoring of kidney function . eGFR <30 mL /minute/1.73 m 2 : Use is contraindicated.

10. For pateints taking metformin measure: A1c 3-6 months Serum creatinine annually Vit.B12 annually

11. α- Glucosidase inhibitors Mechanism of action :↓GI glucose absorption Examples : Acarbose , miglitol , voglibose ↓ A1c by 0.5–0.8% Advantages : Reduce postprandial glycemia Disadvantages : GI flatulence, elevated liver function tests Contraindications: Renal/liver insufficiency

12. Dipeptidyl peptidase IV inhibitors Mechanism of action : Prolong endogenous GLP-1 action; ↑Insulin, ↓glucagon Examples : Alogliptin , linagliptin , saxagliptin , sitagliptin , vildagliptin ↓ A1c by 0.5–0.8% Advantages : Well tolerated, do not cause hypoglycemia Disadvantages: Angioedema / urticarial and immune-mediated dermatologic effects Contraindications: Reduced dose with renal insufficiency

13. Insulin secretagogues : Sulfonylureas Mechanism of action :↑Insulin secretion Glibornuride , Examples : gliclazide , glimepiride , glipizide , gliquidone , glyburide , glyclopyramide ↓ A1c by 1–2% Advantages : Short onset of action, lower postprandial glucose, inexpensive Disadvantages: Hypoglycemia, weight gain Contraindication: Renal/liver insufficiency

14. Gliclazide Immediate-release tablet: Oral:  Initial: 40 to 80 mg once daily with the first main meal . Dosage adjustment:  May increase dose in 40 to 80 mg increments every 1 to 4 weeks if needed to achieve glycemic goals; usual maintenance dose: 40 to 160 mg/day (maximum: 320 mg/day) Note :  Administer doses ≥160 mg/day in 2 divided doses. Modified-release tablet: Oral:  Initial: 30 mg once daily with the first main meal. Dosage adjustment:  May increase dose in 30 mg increments every 1 to 4 weeks if needed to achieve glycemic goals; usual maintenance dose: 30 to 60 mg/day (maximum: 120 mg/day) .

15. Altered kidney function: eGFR >60 mL /minute/1.73 m 2 : No dosage adjustment necessary ( Ref ). eGFR 15 to 60 mL /minute/1.73 m 2 :Use with caution.  eGFR <15 mL /minute/1.73 m 2 :Avoid use if possible

16. Glimepiride Oral:  Initial: 1 to 2 mg once daily with the first main meal; max 8mg/day

17. Altered kidney function eGFR >60 mL /minute/1.73 m 2 : No dosage adjustment necessary. eGFR 15 to 60 mL /minute/1.73 m 2 : Renal clearance of active metabolites may be reduced, leading to increased risk of hypoglycemia; consider initiating at a low dose ( eg , 1 mg daily) and titrating cautiously. eGFR <15 mL /minute/1.73 m 2 : Avoid use

18. Glipizide Immediate release: Oral:  Initial: 2.5 to 5 mg once daily 30 minutes before the first main meal if dose reaches >15mg/day, then split dose BID ; max 40mg/day Extended release: Oral:  Initial: 2.5 to 5 mg once daily with the first main meal;

19. Altered kindey function Oral:  Immediate-release and extended-release tablets: eGFR ≥50 mL /minute/1.73 m 2 : No dose adjustment necessary. eGFR 10 to <50 mL /minute/1.73 m 2 : Initial: 2.5 mg once daily. May cautiously titrate based on glycemic control up to a maximum 20 mg/day . eGFR <10 mL /minute/1.73 m 2 : Avoid use if possible. If necessary, initial dose of 2.5 mg once daily, may cautiously titrate based on glycemic control up to a maximum of 20 mg/day.

20. Insulin secretagogues : Nonsulfonylureas Mechanism of action: ↑Insulin secretion Examples : Mitiglinide , nateglinide , repaglinide ↓ A1c by 0.5–1.0% Advantages : Short onset of action, lower postprandial glucose Disadvantages: Hypoglycemia Contraindication: Renal/liver insufficiency (except repaglinide )

21. Sodium-glucose cotransporter 2 inhibitors Mechanism of action : ↑Renal glucose excretion Examples: Canagliflozin , dapagliflozin , empagliflozin , ertugliflozin ↓A1c by 0.5–1.0 % Advantages: Do not cause hypoglycemia, ↓weight and BP, renal protective, ↓CV events Disadvantages : Urinary and genital infections, polyuria , dehydration, exacerbate tendency to hyperkalemia and DKA Contraindication: Moderate renal insufficiency, insulindeficient DM

22. Canagliflozin – start with 100mg QD before 1 st meal, then increase BID; ↑to max dose 300mg Dapagliflozin - start with 5mg Q AM; then ↑ to max dose 10mg Empagliflozin - start with 10mg daily; can max to 25mg daily

23. SGLT-2 inhibitors are associated with slower progression of kidney disease

24. Thiazolidinediones Mechanism of action: ↓Insulin resistance, ↑glucose utilization Examples : Pioglitazone , rosiglitazone ↓ A1c by 0.5–1.4% Advantages: Lower insulin requirements Disadvantages: Peripheral edema, CHF, weight gain, fractures, macular edema Contraindications: CHF, renal/liver insufficiency

25. Pioglitazone : Oral:  Initial: 15 to 30 mg once daily. Dosage adjustment: May increase in 15 mg/day increments every 4 to 12 weeks if needed to achieve glycemic goals (maximum: 45 mg/day) Discontinue use if signs or symptoms of heart failure develop. Altered kidney function:  Mild to severe impairment: No dosage adjustment necessary

26. Rosiglitazone Oral:  Initial: 4 mg/day as a single dose or in 2 divided doses If response is inadequate after 8 to 12 weeks of treatment, the dosage may be increased to 8 mg/day as a single dose or in 2 divided doses daily; maximum dose: 8 mg/day Kidney Impairment: No dosage adjustment necessary.

27. GLP-1 receptor agonists Mechanism of action : ↑Insulin, ↓glucagon, slow gastric emptying, satiety Examples : Dulaglutide , exenatide , liraglutide , lixisenatide , semaglutide (oral formulation available) ↓ A1c by 0.5–1.0% Advantages : Weight loss, do not cause hypoglycemia (unless combined with another insulin secretagogue or insulin); ↓CV events Disadvantages: Injection, nausea, pancreatitis Contraindication: Renal disease, agents that also slow GI motility; medullary carcinoma of thyroid, pancreatic disease

28. Duloglutide SUBQ:  Initial: 0.75 mg once weekly; may increase to 1.5 mg once weekly after 4 to 8 weeks if needed to achieve glycemic goals. If additional glycemic control is needed, may further increase to 3 mg once weekly after at least 4 weeks on the 1.5 mg weekly dose and then to a maximum of 4.5 mg once weekly after at least 4 weeks on the 3 mg weekly dose. Missed doses:  Missed dose should be administered as soon as possible within 3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.

29. Exenatide Immediate release:  SUBQ:  Initial: 5 mcg twice daily within 60 minutes prior to morning and evening meals (or before the 2 main meals of the day, ≥6 hours apart); may increase to 10 mcg twice daily after 1 month if needed to achieve glycemic goals. Missed dose:  Missed dose should be skipped; resume at the next scheduled dose. Extended release:  SUBQ:  2 mg once weekly without regard to meals. If changing the day of administration is necessary, allow at least 3 days between 2 doses. Missed dose:  Missed dose should be administered as soon as possible if the next scheduled dose is due in ≥3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.

30. Liraglutide SUBQ:  Initial: 0.6 mg once daily for 1 week, then increase to 1.2 mg once daily; if optimal glycemic response is not achieved after an additional week of treatment, may increase further to 1.8 mg once daily. 

31. Kidney Impairment: Adult No dosage adjustment necessary ( Liraglutide and Dulaglutide ) Exenatide CrCl ≥30 mL /minute: No dosage adjustment necessary; use caution with initiation of therapy or when increasing the dose in patients with CrCl 30 to 50 mL /minute; monitor for hypovolemia . CrCl <30 mL /minute: Use is not recommended. ESRD: Use is not recommended.

32. References American diabetes association : Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2023   https://diabetesjournals.org/care/article/46/Supplement_1/S140/148057/9-Pharmacologic-Approaches-to-Glycemic-Treatment American association of clinical endocrinologist: Type 2 management algorithm 2023 https://www.endocrinepractice.org/article/S1530-891X(23)00034-4/fulltext Harrison principles of internal medicine 21 st edition Uptodate 2024