Quick Reference Guide 2/2020 version Management of Type 2 Diabetes Non-insulin and Insulin Therapies Soe Naing, MD, MRCP(UK), FACE Associate Clinical Professor of Medicine Director of Division of Endocrinology Medical Director of Community Diabetes Care Center UCSF-Fresno Medical Education Program Page 1: Overview of glucose-lowering agents Page 2: "Regimen" selection guide Page 3: "Medication class" selection guide Page 4: Prescription page Page 5: CKD and medication dose adjustment Page 6: Medications (brand names) in alphabetical order Page 7: Insulin therapy guide (basic) Page 8: "GLP1 RA and SGLT2" selection guide Page 9: ADA 2020 guide on non-insulin therapy Page 10: AACE 2020 guide on non-insulin therapy Page 11: Human insulin in patients with cost issue Page 12-15: Advanced insulin therapy References: STANDARD OF MEDICAL CARE IN DIABETES 2020 https://care.diabetesjournals.org/content/43/Supplement_1 American Association of Clinical Endocrinologists 2020 Comprehensive Type 2 Diabetes Management Algorithm https://www.aace.com/pdfs/diabetes/algorithm-exec-summary.pdf For digital copy, please visit http://www.fresno.ucsf.edu/internal-medicine/endo_downloads/ or email [email protected]. Naing/2-2020 1 Naing/2-2020 2 Naing/2-2020 3 Comparison of Glucose-Lowering Medications # 1 Use this table to choose a class of medication – Consider the factors in first column, that will impact the medication choice. 4 Major groups Insulin Sensitizers Insulin Providers GLP1-based therapy Glucose Absorption Inhibitor 12 Classes Biguanide Thiazolidinedione Insulin secretagogues Insulin DPP4 GLP-1 Receptor SGLT2 Inhibitors α Glucosidase (Metformin) (Pioglitazone) Inhibitors Agonists Inhibitors Sulfonylurea Glinides Cost Low Low Low Moderate Low - human insulin High High High Moderate High - Analog insulin HYPOglycemia risk↑ No No Yes Yes Yes No No No No Weight Change Loss Gain Gain Gain Gain Neutral Loss Loss Neutral ASCVD + Potential benefit Potential benefit Neutral Neutral Neutral Neutral 1st choice Preferred Preferred add-on if GLP1 Neutral add-on. RA contraindicated. Lira- or Sema-glutide Empa- or Cana-gliflozin SubQ See page 8 for detail See page 8 for detail CHF + Neutral ↑ CHF risk Neutral Neutral ↑ CHF Risk with Preferred add-on if 1st choice - preferred add- Neutral Saxa- & Alo-gliptin SGLT2i contraindicated on if eGFR is adequate. Lira- or Sema-glutide Empa-,Cana- or Dapa- SubQ See page 8 for detail gliflozin – See page 8 for detail CKD + Contraindicated if No dose adjustment Avoid Glyburide Repaglinide Lower doses required Linagliptin – no Preferred add-on if 1st choice - preferred add- Avoid if eGFR (See page 5 for details) (see page 5 for eGFR <30 needed can be used if eGFR ↓ need to adjust dose. SGLT2i contraindicated. on if eGFR is adequate. <30 details) Do not start or to in advanced Others – to reduce Lira- or Sema-glutide Empa-,Cana- or Dapa- reduce current CKD/ESRD. dose. SubQ See page 8 for detail gliflozin- See page 8 for detail dose if eGFR <45. See page 5 for dosing based on eGFR Efficacy (↓A1c) 1 to 2% 1 to 1.5% 1 to 2% 1 to 1.5% No “ceiling” 0.6 to 0.8% 0.8 to 1.6% 0.5-1.0% eGFR dependent 0.5% High High High High Highest Intermediate High Intermediate to High Low Route Oral Oral Oral Oral SQ Oral SQ/Oral Oral Oral Other benefits Extensive Durability, ↑ HDL Extensive experience ↓ Postmeal Universal Well tolerated ↓ Postmeal glucose ↓ BP ↓ Postmeal experience Benefit in NASH glucose Response excursion glucose excursion excursion Other risks Nausea Edema Weight gain Weight gain Weight gain Angioedema Nausea, Vomiting DKA, GU tract infection Flatulence Diarrhea ↑Fracture risk High rate of Frequent Urticaria ↑ Heart rate ↑ K, ↑ LDL, ↑ Cr (brief) Diarrhea Lactic acidosis ? Bladder cancer secondary failure dosing ? Pancreatitis ? Pancreatitis Hypotension, Dehydration Frequent dosing B12 ↓ ? Macular edema ? Arthralgia Medullary thyroid cancer Fournier gangrene ? Bullous pemphigoid in animals ↑risk of amputation/fracture with Canagliflozin Contra- eGFR <30 NYHA III/IV heart Severe renal or Use with caution in PMH or FH of Most SGLT2 inhibitors are Cirrhosis MEN2/Medullary thyroid Inflammatory indication Acidosis failure hepatic impairment patients with a h/o contraindicated if eGFR Hypoxia Active bladder cancer pancreatitis. cancer <30 bowel disease Caution in h/o pancreatitis Dehydration Hepatic impairment (See page 5 for detail) Intestinal or gastroparesis. obstruction. Naing/2-2020 Comparison of Glucose-Lowering Medications # 2 4 Use this table to prescribe a medication from the class chosen in previous table 4 Major groups Insulin Sensitizers Insulin Providers GLP1-based therapy Glucose Absorption Inhibitor 12 Classes Biguanide Thiazolidi- Insulin secretagogues Insulin DPP4 GLP-1 Receptor Agonists SGLT2 Inhibitors α Glucosidase (Metformin) Inhibitors nedione Sulfonylurea Glinides Inhibitors Currently Metformin Pioglitazone Glipizide Repaglinide Meal insulin: Sitagliptin (Januvia) Exenatide (Byetta,Bydureon) Canagliflozin (Invokana) Acarbose (Glucophage, (Actos) (Glucoterol), (Prandin), Novolog/Fiasp, Saxagliptin (Onglyza) Liraglutide (Victoza) Dapagliflozin (Farxiga) (Precose), Available Fortamet, Glimeperide Nateglinide Humalog/Admelog, Linagliptin (Trajenta) Lixisenatide (Adlyxin) Empagliflozin (Jardiance) Miglitol Medications Glumetza) (Amaryl), (Starlix) Apidra, Alogliptin (Nesina) Dulaglutide (Trulicity) Ertugliflozin (Steglatro) (Glyset) Humulin/Novolin R Glyburide Semaglutide (Ozempic) (Brand name) Afrezza inhalor (Micronase, Basal insulin: Semaglutide (Rybelsus) Diabeta, Lantus/Basaglar/ Glynase) Toujeo/, Levemir, Tresiba Humulin/Novolin N Minimum – 500mg qd- Actos Glipizide Prandin No maximum Januvia Byetta 5-10 mcg bid/ac, SubQ Invokana 100-300 mg qam, po Precose or 1000 mg bid, 15-45 mg qd, 2.5-20 mg 0.5-4 mg dose 25-100 mg qam, po Bydureon or Bydureon Bcise Farxiga 5-10 mg qam, po Glycet Maximum dose po po bid/ac, po tid/ac, po Onglyza 2 mg qw, SubQ Jardiance 10-25 mg qam, po 25-100 mg & Glimeperide Starlix 2.5-5 mg qam, po Victoza 0.6-1.8 mg qam, SubQ Steglatro 5-15 mg qam, po tid/ac, po Dosing 1- 8 mg qam 60-120 mg Tradjenta Adlyxin 10-20mcg qam, SubQ Frequency Glyburide tid/ac, po 5 mg qam, po Trulicity 0.75-1.5 mg qw, SubQ 1.25-20mg Nesina Ozempic 0.25-1.0 mg qw, SubQ qam, po 6.25-25mg qam, po Rybelsus 7 or 14 mg qam, PO Available 500, 850, Actos Glipizide Prandin Pens (U-100): Januvia Byetta 5, 10mcg pen Invokana 100, 300 mg Precose or 1000 mg 15, 30, 5, 10 mg 0.5, 1, 2 mg 3ml (300 Units) 25,50,100 mg Bydureon or Bydureon Bcise 2mg Farxiga 5, 10 mg Glycet strength 45 mg Glimeperide Starlix Vial: Onglyza Victoza 0.6, 1.2, 1.8 mg pen Jardiance 10, 25 mg 25,50, 1, 2, 4 mg 60,120 mg 10ml (1000 Units) 2.5, 5 mg Adlyxin 10, 20mcg pen Steglatro 5, 15mg 100 mg Glyburide Tradjenta Trulicity 0.75, 1.5 mg pen 1.25, 2.5, 5mg 5 mg Ozempic 0.25, 0.5, 1.0 mg pen Nesina Rybelsus 7 or 14 mg tablet 6.25,12.5,25 mg Combination Metformin and TZD can be used Do not use Sulfonylurea and Do not use meal Do not use DPP4 inhibitors and GLP1 RA together. together. Glinides together. insulin and insulin secretagogues. Available WITH ACTOS: WITH DPP4 inhibitor: WITH a basal insulin: WITH SGLT2 inhibitor: Actoplus Met XR JanuMet XR (Januvia+metformin) Xultophy Invokamet XR (Invokana+metformin) combination (Actos+Metformin) 50/500, 50/1000, 100/1000 mg, qam Degludec (Tresiba) + liraglutide 50/500, 150/500, 50/1000 or 150/1000 mg, qam (2-in-1) 15/1000, 30/1000mg, qam (XR) Kombiglyze XR(Onglyza+metformin) (Victoza) Xigduo XR (Farxiga+met) medications 15/500, 15/850 mg, bid (generic) 2.5/1000, 5/500, 5/1000 mg, qam 2.5/1000, 5/500, 5/1000, 10/500 or 10/1000 mg, qam Duetact (Actos+Amaryl) Kazano (Nesina+metformin) Soliqua Synjardy XR (Jardiance+met) 30/2, 30/4 mg, qam 12.5/500, 12.5/1000 mg, bid glargine (Lantus) + lixisenatide 5 or 10 or 12.5 or 25/1000 mg, qam Oseni (Nesina+Actos) Oseni (Nesina+Actos) (Adlyxin) Glyxambi (Jardiance+Tradjenta) - 10/5 or 25/5 mg, qam 25/15, 25/30 or 25/45 mg, qam 25/15, 25/30 or 25/45 mg, qam Qtern (Farxiga+Onglyza) - 10/5mg qam Jentadueto (Tradjenta+metformin) Segluromet (Steglatro+Metformin) 2.5/500, 2.5/850, 2.5/1000 mg, bid 2.5/500, 2.5/1000, 7.5/500 or 7.5/1000 mg, bid Steglujan (Steglatro+Januvia) - 5/100 or 15/100 mg, qam Naing/2-2020 5 6 7 Management of Type 2 Diabetes : Guide for Insulin Initiation and Titration Insulin regimens Starting dose Titration Step 1 One injection daily Basal insulin therapy: Patients may adjust the dose by 1 unit every night or with a basal insulin Start 0.2 Unit/kg body weight by 3 units or 10-15% every 3 nights until target fasting To cont’ metformin, GLP1 RA ± other or 10 units QHS. BG of 80-130 mg/dl is achieved. non-insulin agents (Lantus/Toujeo/Basaglar, Levemir, Tresiba or NPH) Consider adding prandial insulin if A1c is not at goal though the patient has been taking at least 0.5 unit/kg of basal insulin or fasting BG has been at goal. Basal+1 regimen: Patients may adjust the prandial insulin dose Add one dose of prandial insulin by 1 unit every day or by 2 units or 10-15% every 3 before main meal of the day. days until 2 hours post-meal BG of 100-160 or next Step 2 Start 0.1 U/kg, 4 units or 10% of current basal dose. pre-meal BG of 80-130 is achieved. Two injections daily (Novolog, Fiasp, Humalog, Admelog, Apidra or Human insulin R) with Basal+1 regimen or Breakfast dose: Pre-mixed insulin Pre-mixed insulin therapy: Patients may adjust the dose by 1 unit every day or Change basal insulin to pre-mixed insulin bid/ac.