University:
West Coast University
Course:
PHAR 742 | IPC Endocrine
Academic year:

2024
Views:

404

Pages:

41
Author:

Asal A.

T2DM Management ORAL MEDICATIONS Pharmacology: covered by Dr. Farris fyi Why Metformin (MTF) has been considered “first line” DOC since the 1950s (ADA and AACE) • • • • • • • • Effects on A1C Absence of weight gain Absence of hypoglycemia Generally < adverse effects High level of acceptance Low cost Titrated to max effective dose over 1-2 months Due to pathophysiology of diabetes and its associated comorbidities, it is now preferred to use newer and more specific forms of therapy (eg, GLP1 RA, SGLT2I can be initiated independent of A1c and MTF therapy, particularly for individuals are high risk for HF, CKD, and/or ASCVD) soon Moe Fortune Metformin (Glucophage, Glucophage XR) Ge SoongBIDoptodooomyBID • • • • 500, 850, 1000 mg tablets 500, 1000 mg ER tablets 500mg/5mL oral solution Dose: Initiate 500 mg QD-BID or 850 mg QD w/meals (max 2550mg for IR and 2000 for ER wasted etffhelpwiolsumptoms Elam Metformin (Glucophage, Glucophage XR) • Boxed warning: lactic acidosis: risk ↑ with hypoxic states (acute HF, sepsis, COPD exacerbation), dehydration, hepatic, or renal Wolontrastdye impairment, age > 65, intravascular iodinated contrast media, alcohol use • Contraindications: eGFR <30 mL/min, acute or chronic metabolic acidosis (included DKA) with or without coma, acute HF • Warning: not recommended to initiate if eGFR 30-45 mL/min, frequent HF exacerbations Nj • Side effects: N/V/D, flatulence, noabdominal cramping • Monitor: Vitamin B 12 deficiency, BG, A1c, renal function Elem • A1C ↓1-2 % • Other FDA indications: GDM, PCOS, T2DM Prevention, etc. • • Switching to XR formulations can improve GI sxs A1c reduction up to 1.5-2% in it's means lot of urination Takenmorons my SGLT 2 Inhibitors ptorinatemoneys Workite • MOA: Sodium-glucose cotransporter 2 in proximal tubules is responsible for glucose reabsorption – SGLT1 and SGLT2 both reabsorb glucose back into system – SGTL1 10%, SGLT2 90% • ↓ glucose reabsorption and ↑ renal glucose excretion • Weight loss • Lower BP • ↓ A1C 0.5-1% SGLT 2 Inhibitors respecianyinptul peripheral • Warning: ↑ risk of leg and foot amputations neuropathy • Ketoacidosis (including fatality) Go sanagloflorin invoked • Side effects – – – – – Hypotension Female genital fungal infections UTI Increase urination Increase LDL • Monitor potassium in patients at risk for hyperkalemia higherriskfor amputation body sotogifiozinsinpenfa Y SGLT 2 Inhibitors COME AfrsenaitiHee.esnespeareontgapped this • Canagliflozin (Invokana) – Start 100mg qdaily off – Can increase to 300 qdaily as needed (available 100, 300 mg tablets) – eGFR 30-59 = 100 mg qdaily – eGFR < 30 mL/min àNot recommended • Empagliflozin (Jardiance) – 10 mg QAM, can ↑ to 25 mg daily – eGFR < 30 àCI • Dapagliflozin (Farxiga) – 5 mg daily in the AM, can ↑ to 10 mg – eGFR < 30 àCI • Ertugliflozin (Steglatro) – 5 mg daily in the AM, can ↑ to 15 mg – eGFR < 30 àCI SGLT 2 Inhibitors • Prior to initiation: – Assess renal function before initiating and as clinically indicated – Consider factors that may increase the risk of amputation (eg, history of previous amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers) • Canagliflozin t fromit stay away – Correct volume depletion ja – Consider factors that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse – Consider factors that contribute to fracture risk (frail frame, osteoporosis or osteopenia) Ipf C infullerforalogger Y Semaglutide (Rybelsus) • Note: Semaglutide is generic name for PO Rybelsus, SC Ozempic, and SC Wegovy (approved for chronic weight mgmt.) E • Rybelsus be used as an adjunctive agent or alternative monotherapy for patients who fail initial therapy with lifestyle intervention and metformin or who cannot take metformin. DA• May be preferred in patients who have or are at risk for appreed Gr atherosclerotic cardiovascular disease (OZEMPIC only), t when weight loss is desired, and/or in patients with an ASCID HbA relatively far from goal (eg, HbA 9% to 10%) 1c 1c Semaglutide (Rybelsus) dose starting • 3me mg once daily for 30 days, then increase to 7 mg once daily; may increase to 14 mg once daily after 30 days on the 7 mg dose if needed to achieve glycemic goals. • Initial dose (3 mg daily) is intended to reduce GI symptoms; it does not provide effective glycemic control. • Administer on an empty stomach, ≥30 minutes before theEtat first food, beverage, or other oral medications of the day with ≤4 oz of plain water only. • Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor og Ya • May require a dose reduction of insulin and/or insulin secretagogues to avoid hypoglycemia Dppland01PM DapliantMoa so usuallytake offtheDpp4 llackofaddatid Beretit Semaglutide (Rybelsus) Boxed warning: Risk of thyroid C-cell tumors seeitinmicenothumanyet Contraindications: Personal or family history of medullary thyroid carcinoma (MTC); patients with multiple endocrine neoplasia syndrome type 2 (MEN2) GLP-1 Agonists • Adverse Effects • Major: GI – 30-45% nausea & vomiting – Hypoglycemia when used with secretagogue or insulin IEEE • AKI, Pancreatitis • (↓ secretagogue or insulin by ~20%) • Weight loss over 6 months ~ 4-6 lbs, more with higher doses • Diabetic retinopathy complications have been reported in patients with type 2 diabetes and high cardiovascular risks; increased risk in patients with a history of diabetic retinopathy at baseline. t Monitoring is recommended. – Rapid improvement in glucose control may temporarily worsen diabetic retinopathy DPP4 Inhibitors • MOA: – Unlike GLP-1 agonist, has little to no effect on gastric emptying time or satiety 8 – Increases glucose-stimulated insulin secretion – Causes glucose-stimulated glucagon suppression • ↓ A1C by 0.5-0.9% DPP4 Inhibitors • • • • Sitagliptin (Januvia®) approved 2006 Saxagliptin (Onglyza®) approved 2009 Linagliptin (Tradjenta®) approved 2011 Alogliptin (Nesina®) approved 2013 Eton Sitagliptin (Januvia) • • • • Eat AA 25, 50, 100 mg tablets forNoot Recommended dose = 100noo mg qdaily Dose with or without food Adjust dose in moderate-severe renal disease: – 50 mg qdaily: • CrCl 30-50ml/min – 25 mg qdaily: • CrCl<30ml/min • Do not use if severe hepatic insufficiency • No CYP interactions Saxagliptin (Onglyza) • • • • 2.5, 5 mg tablets Recommended dose = 5 mg qdaily Dose with or without food Adjust dose in moderate-severe renal disease: – 2.5 mg qdaily: • CrCl< 45 ml/min • No dosage adjustment needed for hepatic impairment Saxagliptin DDI Fyi • When co-administered with strong CYP3A4/5 inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin)... – Recommended dose is 2.5 mg qdaily Linagliptin (Tradjenta) • • • • • • 5 mg tablets Recommended dose = 5 mg qdaily Dose with or without food NO RENAL OR HEPATIC ADJUSTMENT NEEDED! Weak to moderate inhibitor of CYP3A4 CYP3A4 inducers will decrease the serum concentration of linagliptin Alogliptin (Nesina) • • • • • • • 6.25, 12.5, 25 mg Recommended dose = 25mg daily With or without food CrCl 30-59 = 12.5 mg CrCl < 30 = 6.25 mg Do not use if severe hepatic insufficiency No CYP interactions • Note: The combined use of GLP-1 RAs, Tirzepatide, and/or DPP-4 Inhibitors (eg, Sitagliptan) NOT recommended due to their similar MOA. DPP IV Inhibitors ADRs Exam I • Upper respiratory infection 6.3%or coldlikesymptom • Nasopharyngitis 5.2% • Headache 5.1% • Hypoglycemia similar to placebo • When combined with metformin or glitazone = no change in risk of hypoglycemia • When combined with secretagogues ↑ risk of hypoglycemia • Angioedema t Agecause Warnings musclepain • Arthralgiaso Alsopioglitazone • Pancreatitis seeof HF (↑risk in pts with hx of HF or renal • Saxagliptin and alogliptin: risk impairment) • Alogliptin: hepatotoxicity Thiazolidinediones • MOA: Enhancing peripheral insulin sensitivity, especially at the muscle and adipose tissue, via activation of PPAR (peroxisomeproliferatoractivated receptor gamma) – A1C ~ 1-1.5% monotherapy – Does not cause hypoglycemia – Onset of effect takes 1-2 weeks, although maximum effect not seen until 2-3 months ask It m TZDs A Egg • Pioglitazone start dose 15-30 mg qdaily (45 mg max) – 15, 30, 45 mg tablets – ↓ TG, ↑ HDL, no change to TC or LDL – Metabolized by CYP 3A4, 2C8 TZDs • Major side effect: Weight gain and fluid retention (peripheral edema) – Weight gain of 2-12 lbs, which is dose-dependent • Increase incidence of bone fractures in women • Hepatic dysfunction – Fatigue, anorexia, nausea, vomiting, abdominal pain, dark urine, or jaundice TZDs • Contraindications: – Avoid in patients with CHF (New York Heart Association class III or IV) – In class II, initiate pioglitazone at lowest dose, and monitor CHF symptoms – Avoid in hepatic impairment with LFTs> 2.5 times the ULN • Monitoring: – LFTs every 2 months for 1 year; periodically thereafter • No reliance on renal excretion Sulfonylureas • Primary MOA = stimulate insulin release from pancreatic β cells (secretagogue) • ↓ A1C ~ 1.5% Pg meal TakeBefore Sulfonylureas as • Major SE: Hypoglycemia that'swhynotfirsttime – Severe episodes with need for assistance, coma, or seizure are infrequent – More common in elderly – New/shorter acting sulfonlyureas < risk •t “Sulfa” allergy-sulfonamide allergy Exam • Weight gain ~ 4 lbs with initiation of therapy • Sun sensitivity Sulfonylureas • Glipizide – 5, 10 mg tablets • 30 mins before meals • 5-40 mg/day divided in 1-2 doses Fy just Inytay're Not good BEERS for list – 2.5, 5, 10 mg XL tablets • Take with breakfast • 2.5-20 mg/day • Glimepiride – 1, 2, 4 mg tablets – 1-8 mg once daily with meal • Glyburide – – – – 1.25, 2.5, 5 mg tablets 1.25-20 mg/day divided in 1-2 doses with meals Not recommended for CrCl< 50mL/min (weakly active metabolite) Not preferred agent eddy I Sulfonylureas & Hypoglycemia • Longer-acting agents = ↑ risk – 1st generation (not used anymore) – Glyburideorhighestrisk forhypogene – Sustained-release glipizide Meglitinides (glinides) • MOA: Stimulate a rapid but short-lived release of insulin that lasts for 1-2 hours, therefore should be used to target postprandial glucose levels • ↓ A1C by 0.5-1% After money • Advantages: – Good for patients who are not meal- regimented – OK if sulfa allergic • Disadvantages: – Compliance may be problematic due to multiple daily – Patients having a poor response to sulfonylurea therapy are not likely to respond if these drugs are added Meglitinides • Nateglinide – 60, 120 mg tablets – Initiate 60 mg TID w/ meals (max 360 mg/d) T • Repaglinide – 0.5, 1, 2 mg tablets – Initiate 0.5 mg TID w/ meals (max 16 mg/d) Meglitinides • Side Effects: – Hypoglycemia: less hypoglycemia than SFU – Weight gain • Used with caution in patients with hepatic impairment – Primarily metabolized by the liver to inactive product • Nateglinide: – OK to use at regular doses in severe renal failure • Repaglinide: – Reduce dose in severe renal failure • Skip dose if meal is skipped α-Glucosidase Inhibitors MOA: Delay intestinal glucose absorption via inhibition of enzyme that breaks down CHOs (poly to monosaccharides); Reduces post-prandial glucose without causing hypoglycemia; ↓ A1C by 0.5-1% Side Effects:Examcarbohydrates Since CHOs are absorbed in distal intestine, malabsorption and weight loss do not occur. However, ↑ delivery of CHOs to colon = ↑ gas production and GI symptoms • GI (more common in acarbose): Flatulence (41.5-77%), Diarrhea (28.7-33%), Abdominal I pain(11.7-21%) • • Elevated LFTs (acarbose only):Monitor AST & ALT every 3 months for first year Does not cause hypoglycemia by itself Contraindicated in: - Inflammatory bowel disease, colonic ulceration, or partial intestinal obstruction, and those predisposed to intestinal obstruction - Chronic intestinal diseases associated with marked disorders of digestion or absorption, or with conditions that may deteriorate as a result of increased gas formation in the intestine α-Glucosidase Inhibitors • • • • Max response observed at 6 months Acarbose 25, 50, 100 mg tabs Miglitol 25, 50, 100 mg tabs Dose: – 25mg TID w/ first bite of each meal (300 mg max) – Max acarbose dose for < 60 kg = 150 mg/d • Avoid when SCr > 2.0mg/dL – Not studied Meet Theresa Theresa • Theresa is a 49 y/o AA female. She arrives at diabetes management clinic for a f/u. But as • Ht: 5’4, weight 205, BMI 35.3 kg/m2. • FH: type 2 diabetes, heart disease, and stroke. • PMH: Hypertension, diabetes, and hyperlipidemia. • HbA1c: 9.0% , FPG 183 mg/dL. • She is unable to tolerate metformin due to GI side effects. She has failed IR and ER formulation. • What is Theresa’s eAG? A 2430 190 27 30 M • What would the most appropriate therapy for for Theresa? Boyz • How would you initiate treatment? oral orinjection start w store • What are her glycemic goals? no Ryblesusangonceaday so onempty ÉÉÉ• How would you counsel this patient? w Trelicity rots so Eff pick ozempic ao.rs is Mong're so 2Sng Theresa Suttonslanosegroup • Theresa was started on glipizide 10 mg BID, sitagliptin 100 mg. • She is back in clinic today for a follow up and reports that the day before she was working out in the yard and became dizzy, shaky, sweaty, and confused. • She checked BG, it was 43 mg/dL. • She consumed 6 oz of orange juice and rechecked in 15 minutes. The result is 147 mg/dL. slipi ate no • What is the likely cause of Theresa’s hypoglycemia? • How would you adjust her dose? godown to SISBID spinsaline Adcabove • • • • 1 Bs 351 satabolicsumptcloss a lot ofmagnet 76 y/o M, recently diagnosed with T2DM. PMH: HF with frequent exacerbations, HTN, dyslipidemia, COPD with frequent exacerbations A1C: 8.3% goals7 fastPoBo aftermeal 180 According to ADA 2024, what is the best medication to start at this time? SOLT 2 Boo f A. Metformin w B. Pioglitazone contra Hf C. Empagliflozin isordinal D. Basaglar closaling • • • • Better option MG 57 y/o male diagnosed with type 2 diabetes based on his labs. He receives diabetes education and dietary counseling. At this time, his ophthalmoscopic examination and urinalysis are normal, and no microalbuminuria is present. Results from an exercise stress test are normal. The patient returns for follow-up testing 4 months later. He continues to smoke but claims he has been compliant with his diet; however, his weight is unchanged 80130 Repeated laboratory testing reveals a fasting blood glucose level of 210 mg/dL. His glycosylated hemoglobin level has increased from 7.2 mg/dL at baseline to 8.3 mg/dL. Which therapeutic measure would be most appropriate at this time A. B. C. D. Begin therapy with insulin Begin therapy with metformin Begin therapy with sitagliptin Try 6 more months of behavior modification sinjardic a • • • • • • sardine t metformin A 56 y/o female has uncontrolled T2DM, while taking metformin 1,000 mg BID, Januvia 100 mg daily, and following life style modifications. metformin A1C: 8.9 % 0 Kana CrCl: 96 mL/min Into 504 At the last visit her regiment was changed to Invokamet 150/1000 mg BID and Januvia 100 mg daily SOLT n She is in clinic today complaining of acute onset of UTI. zine Which agent is most likely the reason for it?

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