Day 1 Mini Review

Day 1 Mini Review • • • • Gold standard for dx diabetes? • What can skew A1c? Gold standard for diabetes dx for pregnant patients. Explain • What are risk factors for diabetes? the process • Who should be screened for diabetes? (think 18:35 rule) When should we recheck A1c if uncontrolled? What is diagnostic FBG and A1c for prediabetes? • • What is diagnostic FBG and A1c for diabetes? Treatment goals: What is goal a1c for MOST patients with diabetes? • • Treatment goals: What is goal FBG and 2-hr PP for MOST patients with diabetes? Treatment goals: what is the BP goal? • • • First line agents for BP control in DM? Who should get an ACEI or ARB with DM? Cholesterol mgmt. recommendations? • Explain testing for diagnosis of diabetes • How do you calculate eAG? • Name microvascular complications associated with DM • Name macrovascular complications associated with DM • List examples of ASCVD • Type 1 vs Type 2 (general) • List drugs that can induce hyperglycemia • FDA approved drugs for neuropathy? • Vaccinations for DM Oral Medications • – Metformin (Glucophage® Riomet®, Fortamet®, Glucophage XR® Glumetza®) Max effective dose IR vs XR? • • • Canagliflozin (Invokana®) Dapagliflozin (Farxiga®) Empagliflozin (Jardiance®) Ertugliflozin (Steglatro®) Starting and max dose, CI • • GLP1RA DPP-4 Inhibitors – – – – (Januvia®) Sitagliptin Saxagliptin (Onglyza®) Linagliptin (Tradjenta®) Alogliptin (Nesina®) Thiazolidinediones – Pioglitazone (Actos®) • Meglitinides Januvia dosing, ADRs, Renal? ismestout mate Alpha-glucosidase Inhibitors – Acarbose (Precose®) – Miglitol (Glycet®) – Semaglutide (Rybelsus®) • Sulfonylureas – Glimepiride (Amaryl®) – Glipizide (Glucotrol®, Glucotrol XL®, Glipizide XL®) – Glyburide (Glynase®) SGLT-2 Inhibitors – – – – Starting and max doses (JIF) Counsel and starting dose Biguanides ADRs, counseling, who is high risk? Weight effects – Repaglinide (Prandin®) – Nateglinide (Starlix®) Day 2 Mini Review • • ADA 2024 Wholesome individualized approach Any Proteinuria (UACR >30; Renal Protection)- Think BP Meds CKD + Proteinuria Treatment? Think DM Meds Most patients at baseline are on: Think historical 1st line Med Glucose-Lowering Effect- Very High, High, Intermediate Weight-loss Efficacy- Very High, High, Intermediate • Why is Metformin “popular”? • • • • • Metformin boxed warning • Metformin CrCl cut-off • Metformin major ADR and how to manage (2 ways) • Metformin typically HELD upon hospital admission due to: • Long-term Metformin can cause which vitamin deficiency? • “Max effective dose” of Metformin? • Is Rybelsus FDA approved for CVD benefit? • How should a patient take Rybelsus? • Is Rybelsus and Januvia drug combination contraindicated? • Patients with personal or family history of which _____ cancer should avoid _______ ? • GLP-1 adverse effects • Warning with SGLT2Is? Think feet (which drug specifically)? • Take SGLT2Is in the AM because _____ • Common side effect of SGLT2I knowhowoftenyouhereto usetheseinjectable Injectable Medications • GLP1RA How often administered, VOT starting and max dose, risks, BBW – – – – – – Exenatide (Byetta®) Liraglutide (Victoza®) Exenatide XR (Bydureon®) Dulaglutide (Trulicity®) Lixisenatide (Adlyxin®) Semaglutide (Ozempic®) • GIP/GLP1RA Starting and max dose – Tirzepatide (Mounjaro) FDA Approved 2022 • Amylin Analog – Pramlintide (Symlin®) • Rapid Acting Insulin – Lispro (Humalog®) – Aspart (Novolog®) – Glulisine (Apidra®) • Short Acting Insulin – Insulin Regular (Humulin R®, Novolin R®) • Intermediate Acting Insulin – Insulin NPH (Humulin N®, Novolin N®) • Long Acting Insulin – Glargine (Lantus®, Basaglar®, Toujeo® SoloStar®) – Detemir (Levemir®) – Degludec (Tresiba®) A taws Therapy Selection Based on Comorbidities – 8100T een Avoid Coronary Disease • Preferred: GLP1RA, SGLT2i +/- metformin Trulinity oZempic Rybersus • FDA approved CVD benefit (GLP-1): dulaglutide, liraglutide, semaglutide (SUBQ) • FDA approved CVD benefit (SGLT2I): canagliflozin, empagliflozin Heart Failure Invoking sardine NotFDAfo • Avoid TZDspiogcitazone diabetes • Preferred: SGLT2i (FDA approved HF benefit: dapagliflozin, empagliflozin, sotagliflozin) • Note: Sotagliflozin is the first dual sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor approved for CV risk reduction and heart failure; not FDA approved for Diabetes (see next slide) • Evidence for benefit: canagliflozin, ertugliflozin – t atIIptin It Id MR ing Renal disease Diabetickidneydisage invokona me • Preferred: SGLT2i (FDA approved renal benefit: canagliflozin (DKD), dapagliflozin (CKD)) • Evidence for renal benefit (SGLT2I): empagliflozin • Evidence for renal benefit (GLP-1): dulaglutide, liraglutide, semaglutide jardional needdose • ↑Increased risk of hypoglycemia • Metformin and lactic acidosis adjusts emposty • Renal dose adjustment – Liver dysfunction: Insulin DOC – Hypoglycemia • Use with caution: SFU and insulins – Pregnancy: Insulin DOC – tard I Sotagliflozin (Inpefa) BYOM- Bring Your Own Mnemonics – Coronary Disease + DM • FDA approved CVD benefit (GLP-1): dulaglutide, liraglutide, semaglutide (SUBQ) • FDA approved CVD benefit (SGLT2I): canagliflozin, empagliflozin • “JIVOT” – Heart Failure + DM • Preferred: SGLT2i (FDA approved HF benefit: dapagliflozin, empagliflozin) • “Just For Heart Failure” – Renal disease + DM • Preferred: SGLT2i (FDA approved renal benefit: canagliflozin (DKD), dapagliflozin jaudiong(CKD)) • “IF kidneys need protection” empty Therapy Selection Weight – Majority of T2DM patients overweight/obese • Weight gain from insulin, SFU, meglitinides may increase insulin resistance • Weight gain from TZD decreases insulin resistance – Intensive lifestyle program: Diet/exercise, low-carb – GLP1-RA and GLP-1/GIP-RA – SGLT2i – Metformin – Bariatric surgery jo Therapy Selection Age: Older adults ≥ 75 - Reduced life expectancy – – – – Higher CVD burden Reduced GFR At risk for adverse events from polypharmacy More likely to be compromised from hypoglycemia èLess ambitious targets • HbA1c <7.5–8.0% if tighter targets not easily achieved • Focus on drug safety ~ A1c % Reductions Drug ~ A1c % Reduction GLP-1/GIP RA (Mounjaro) 1.7-2.3%+ GLP-1 Ras (highest glucose0.7-2.1%+ lowering efficacy with highdose dulaglutide, semaglutide) Insulin 0.9 to 1.2% or more Metformin (MTF) 1.5-2% SFUs 1.5-2% TZDs 1-1.5% SGLT2Is 0.5-1% DPP-4 Is 0.5-0.9% bacowest Fyi kindofknow livagleetidelvictotal 2 PNozings look the was • P.A. is a 55-year-old woman with a history of T2DM, hypertension, hyperlipidemia, and chronic urinary tract infections. She tolerated metformin well but has noticed an increase in A1C values during the past 6–9 months. • A review of blood glucose (BG) readings reveals a record of fasting blood glucose (FBG) values at 140–190 mg/dL and premeal BG values at 180–260 mg/dL. • In addition, today’s laboratory values include the following: • A1C 8.4%; AST 28 U/L (RR 5–30 U/L); ALT 35 U/L (RR 5–40 U/L) • SCr: 1.4 mg/dL 668 • eGFR: 52 mL/ minute/1.73 m2. Me 2) with changes in her regimen. • P.A. is concerned about weight gain [BMI] = 31 kg/m • What is the most appropriate therapeutic change for P.A.? A. Discontinue metformin because of poor renal function and start glipizide B. Start pioglitazone 15 mg daily and titrate to 45 mg daily C. Start liraglutide 0.6 mg subcutaneously every day, with a goal of titrating to a dose of 1.8 mg every day, to her current regimen. sordino 10 mg in the morning, with a goal of titrating to a dose of 25 D. Start empagliflozin mg, to her current regimen. Ma f that'swhynot • • • • • • A 65-year-old woman with a medical history of osteopenia and T2DM diagnosed about 3 years ago is currently treated with vitamin D3 and metformin. met for The patient notes that her FPGs range from 180–200 mg/dL. Sulfa allergy (+) Normal and hepatic function She states that she will never try insulin because she fears needles. Which medication should be added to the patient’s current therapy? A. Sitagliptin B. Liraglutide C. Canagliflozin D. Glipizide A with c YE Which of the following agents require LFT TED grandest • inhibitors monitoring? (SELECT ALL THAT APPLY) a. b. c. d. Miglitol Pioglitazone Alogliptin Dapagliflozin traders • Which of the following is a common adverse effect of linagliptin when used as monotherapy? (SELECT ALL THAT APPLY) y or upperrespiratory URTI tractinfection a. b. UTI c. Weight gain d. Angiodema satin SFU • Which of the following can cause hypoglycemia? (SELECT ALL THAT APPLY) mestitinides A. B. C. D. Glucophage Glucotrol Starlix Glynase • A.J is a 68 y/o female with T2DM poorly controlled on metformin monotherapy. She has a history of medullary thyroid carcinoma, to 564 HF, depression. GL.pt • eGFR: 50 mL/min/1.73 m2 • Which of the following medications would be the best option as an add on therapy? A. B. C. D. Pioglitazone Dapagliflozin Saxagliptin Dulaglutide Important yo Glp moungar Dpp • What antihyperglycemic agents should be avoided in patients with a history of pancreatitis? (SELECT ALL THAT APPLY) a. b. c. d. Glucotrol XL Actos Tradjenta Trulicity pancreatitis 618 9,61 pl Dpp mongrel T2DM Management INJECTABLE MEDICATIONS GLP-1 Agonists • MOA: Binds avidly to GLP-1 receptor on the pancreatic β cell and ↑ glucose-mediated insulin secretion • Incretins—glucose dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin secretion, inappropriate glucagon secretion, and slows gastric emptying • GIP also promotes energy storage via direct actions on adipose tissue • ↑ Satiety • ↓ A1C by 1-1.5% GLP-1 Agonists • Exenatide (Byetta)- BID • – 2 mg SQ q 7 days without regard to time or meals – Inject immediately after powder is suspended – 5 mcg SQ BID X 1 month, then 10 mcg BID – Must inject within 60 minutes before meal • Liraglutide (Victoza)- daily – 0.6 mg SQ qdaily X 1 week, then 1.2 mg – 1.8 mg can be used if more response needed – Inject at same time each day w/o regard to meal • Lixisenatide (Adlyxin)- daily – 10 mcg SC daily X 14 days, then 20 mcg daily – Must inject within 60 minutes before meal Exenatide XR (Bydureon)-weekly • Semagluide (Ozempic)- weekly • Dulaglutide (Trulicity)- weekly – 0.25 mg SC once weekly x 4 weeks, ↑ to 0.5 mg SC once weekly, – can ↑to 1 mg SC weekly – 0.75 mg SC once weekly, can ↑to 4.5 mg SC once weekly GLP-1 Agonists • • Adverse Effects Major: GI – 30-45% nausea & vomiting – Hypoglycemia when used with secretagogue or insulin • (↓ secretagogue or insulin by ~20%) • • AKI, Pancreatitis Weight loss over 6 months ~ 4-6 lbs – May be result of GI adverse effects • • • • Boxed Warning: Thyroid C-Cell Cancer in rats Caution: When taking medications that require rapid GI absorption or are dose-dependent (advise to take 1 hour before GLP-1 injection): eg, Antibiotics, Oral contraceptives Not recommended in patient with severe GI disease and gastroparesis Note: The combined use of GLP-1 RAs, Tirzepatide, and/or DPP-4 Inhibitors (eg, Sitagliptan) NOT recommended due to their similar MOA. GLP-1 Agonists Advantages • Target multiple defects of T2DM, including those not addressed by traditional medications • Lack of hypoglycemia (when insulin reduced) • Favorable effects on weight • May affect disease progression through Beta cell preservation? Disadvantages • Cost • Injection • Severe nausea • Unknown long-term effects Blondigenk Know GLP-1/GIP Agonist- Mounjaro • MOA: Incretins—glucose dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin secretion, inappropriate glucagon secretion, and slows gastric emptying • GIP also promotes energy storage via direct actions on adipose tissue • ↑ Satiety • ↓ A1C by 1.7-2.3% • Weight loss Effects as compared to GLP-1s: Mounjaro >> Ozempic / high-dose Trulicity > other GLP-1 RAs GLP-1/GIP Agonist- Mounjaro • SUBQ: Initial: 2.5 mg once weekly for 4 weeks, then increase to 5 mg once weekly. May increase dose in 2.5 mg/week increments every 4 weeks if needed to achieve glycemic goals (maximum weekly dose: 15 mg/week). Note: The lower initial dose (2.5 mg weekly) is intended to reduce GI symptoms; it does not provide effective glycemic control. If changing the day of administration is necessary, allow at least 72 hours between 2 doses. • ADR: Major- GI • No hepatic or renal adjustment • Has not been studied in patients with history of pancreatitis • Boxed Warning: Risk of thyroid C-cell tumors • Note: The combined use of GLP-1 RAs, Tirzepatide, and/or DPP-4 Inhibitors (eg, Sitagliptan) NOT recommended due to their similar MOA. GLP-1/GIP Agonist Pramlintide (Symlin) • Approved in 2005 • Synthetic analog of β cell amylin – Co-secreted with insulin in response to food • • • • • • Used in type 1 and type 2 DM Slows gastric emptying Inhibits glucagon production Promotes satiety ↓ postprandial glucose Used as adjunctive therapy with bolus insulin – To reduce insulin need Pramlintide (Symlin) Fyi • Must ↓ insulin bolus and/or mixed dose by 50% (severe hypoglycemia) • Dosing for type 1: – Start 15 mcg SQ before major meals: TID – Titrate by 15 mcg to attain maintenance dose of 30-60 mcg before major meals: TID – Titrate based on tolerance of no nausea for 3 days • Dosing for type 2: – Start 60 mcg SQ before major meals: TID – Titrate to 120 mcg after 3-7 days of no nausea Pramlintide (Symlin)y Amylin analog • Adverse effects: – Major: nausea/vomiting in ~ 30% – Hypoglycemia (unless insulin reduced) • Weight loss over 6 months ~ 2-3 lbs2 – May be result of GI adverse effects • ↓ A1C by 0.5-1% • Drug interactions: – Do not use with meds that ↓ GI motility (anticholinergics, α-glucosidase inhibitors) Clinical Considerations Drug classes Contraindicated if Metformin, SGLT2 eGFR or CrCl < 30 mL/min inhibitors, exenatide, glyburide TZDs, alogliptin, saxagliptin Heart failure Canagliflozin Peripheral neuropathy, PAD of diabetic foot ulcers GLP-1 agonists, GLP-1/GIP Gastroparesis or other GI RA, pramlintide disorder SUs Sulfa allergy SUs G6PD deficiency Clinical Considerations cont. Drugs/ Drug Classes Metformin TZDs, alogliptin SGLT2 inhibitors Canagliflozin (hyperkalemia), insulin (hypokalemia) DPP4-inhibitors, GLP-1 agonists (not studied in GLP-1/GIP RA) DPP4 –inhibitors, SUs SGLT2-inhibitors Pioglitazone, dapagliflozin (bladder cancer) GLP-1 agonists (thyroid cancer) Major Risks Lactic acidosis Hepatotoxicity hypotension/dehydration, UTI/genital infections K abnormalities Pancreatitis Hypersensitivity reactions Ketoacidosis Cancer Intervention %A1C↓ Advantages Insulin ●●●●● No limit dose, low $, ↓ Sulfonylureas Disadvantages microvascular Injections, stigma, monitoring, hypoglycemia, weight gain, analogs high $ ●●● Low $, experience, ↓ microvascular Weight gain, hypoglycemia, limited efficacy TZDs ●● No lows, improves lipid profile, maybe lower MI risk Fluid retention, CHF, weight gain, bone fractures, bladder CA GLP-1 RA, GLP-1/GIP RA ●●●●● Weight loss, no lows, DPP-4 Inhibitors ● Weight neutral, no lows, well tolerated Less experience, urticaria, angioedema, pancreatitis, high $ Meglitinides ● Dosing flexibility, ↓ post prandial glucose TID, hypoglycemia, weight gain, high $ Weight neutral, ↓ post prandial glucose GI SE, TID, moderate $ may ↑ B- cell function α-glucosidase ● inhibitors Injections, GI SE, high $, less experience, thyroid tumors question Combination Products Metformin + SU Metformin/glipizide Meformin + Meglitinide Metformin/repaglinide (PrandiMet) Metformin +TZD Metformin/pioglitazone (Actoplus Met, Actoplus Met XR) Metformin/rosiglitazone SU+TZD Glimepiride/pioglitazone (Duetact) Glimepiride/rosiglitazone Metformin+ DPP4 Inhibitor Metfromin/alogluiptin (Kazano) Metformin/linagliptin (Jentadueto, (JentaduetoXR) Metformin/sitagliptin (Janumet, Janumet XR) Metfromin/saxagliptin (Kombiglyze XR) DPP4 Inhibitor + TZD Alogliptin/pioglitazone (Oseni) Metformin + SGLT2 Inhibitor Metformin/canagliflozin (Invokament, Invokamet XR) Metformin/dapagliflozin (Xigduo XR) Metformin/empagliflozin (Synjardy, Synjardy XR) DPP4 Inhibitor + SGLT 2 Inhibitor Linagliptin/empagliflozin (Glyxambi) Saxagliptin/dapagliflozin (Qtern) GLP1 Agonist + Long –Acting Insulin * Liraglutide/insulin degludec ( Xultophy) Lixisenatide/insluin glragine (Soliqua) * Newest combinatuion produts engine hype 2Gt • • • • • • • kidney Day 3 Mini Review FDA approved CVD benefit FDA approved HF benefit FDA approved CKD benefit Glucose-Lowering Effect- Very High, High, Intermediate Weight-loss Efficacy- Very High, High, Intermediate What new drug(s) did ADA 2023/2024 add for DM? What new drug for HFPEF and HFPREF?