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Title Slide addTitleSlide( "Oral Hypoglycemic Agents", "Complete Clinical Pharmacology Reference for Medical & Pharmacy Students" ); // 2. Agenda / Overview contentSlide("Lecture Overview", [ "Introduction & Pathophysiology of Type 2 Diabetes", "Overview of Drug Classes (9 classes)", "Biguanides - Metformin (first-line agent)", "Sulfonylureas (SUs) - Mechanisms & Safety", "Meglitinides (Glinides)", "Thiazolidinediones (TZDs / Glitazones)", "DPP-4 Inhibitors (Gliptins)", "SGLT2 Inhibitors (Gliflozins) - Cardiorenal Focus", "Alpha-Glucosidase Inhibitors", "Other Agents: Bile Acid Sequestrants & Dopamine Agonists", "Treatment Escalation Algorithm & Individualization", "Monitoring Schedule & HbA1c Targets", "Critical Clinical Caveats & High-Yield Exam Points", ], { fontSize: 13.5 }); // 3. Pathophysiology overview contentSlide("Pathophysiology of T2DM - Drug Targets", [ "Insulin resistance: peripheral tissues (muscle, fat) and liver do not respond normally to insulin", "Beta-cell dysfunction: progressive loss of insulin secretory capacity over years", "Glucotoxicity: chronic hyperglycemia further impairs beta-cell function", "Incretin deficiency: reduced GLP-1 / GIP effect, blunted post-meal insulin secretion", "Increased glucagon: alpha-cell dysregulation raises hepatic glucose output", "Renal glucose reabsorption: kidneys recover glucose that should be excreted", "EACH drug class corrects one or more of these defects - understanding the target predicts efficacy, side effects, and contraindications", ]); // 4. Drug Classes Overview addSectionDivider("Drug Classes at a Glance", C.navy); // 5. Classes summary table tableSlide( "9 Major Classes of Oral Hypoglycemic Agents", ["Class", "Key Drug(s)", "Main Mechanism", "HbA1c Reduction"], [ ["Biguanides", "Metformin", "Suppress hepatic gluconeogenesis (AMPK)", "1.5-2.0%"], ["Sulfonylureas", "Glipizide, Glimepiride, Glyburide", "Close KATP channels → insulin secretion", "1.0-2.0%"], ["Meglitinides", "Repaglinide, Nateglinide", "Short-acting KATP closure (postprandial)", "0.5-1.5%"], ["TZDs", "Pioglitazone, Rosiglitazone", "PPARγ agonist → insulin sensitizer", "0.7-1.0%"], ["DPP-4 Inhibitors", "Sitagliptin, Linagliptin", "Prolong incretin (GLP-1/GIP) action", "0.5-1.0%"], ["SGLT2 Inhibitors", "Empagliflozin, Dapagliflozin", "Block renal glucose reabsorption", "0.7-1.0%"], ["Alpha-Glucosidase Inhibitors", "Acarbose, Miglitol", "Delay carbohydrate digestion", "0.5-0.8%"], ["Bile Acid Sequestrants", "Colesevelam", "Unclear; also lowers LDL-C", "~0.5%"], ["Dopamine Agonists", "Bromocriptine", "Reset hypothalamic circadian rhythm", "~0.5%"], ], [2.0, 2.2, 3.0, 2.2] ); // ─── METFORMIN ─────────────────────────────────────────────────────────── addSectionDivider("1. Biguanides\nMetformin", C.navy); // 6. Metformin mechanism contentSlide("Metformin - Mechanism of Action", [ "Activates AMP-activated protein kinase (AMPK) in the liver", " → Suppresses hepatic gluconeogenesis and glycogenolysis (primary effect)", "Improves peripheral insulin sensitivity (muscle)", "Reduces intestinal glucose absorption (minor contribution)", "Does NOT stimulate insulin secretion - no hypoglycemia risk when used alone", "Requires functional gut microbiota (gut-AMPK pathway is partly microbiome-mediated)", "UKPDS legacy: reduces cardiovascular events, possible anti-cancer properties", ]); // 7. Metformin dosing contentSlide("Metformin - Dosing & Formulations", [ "Starting dose: 500 mg once or twice daily with meals (OR 850 mg once daily)", "Titrate every 1-2 weeks to minimize GI side effects", "Maximum effective dose: 2000-2550 mg/day", "Extended-release (XR / ER) formulations: better GI tolerability, once-daily dosing", "Always take with food to reduce GI side effects", "Onset: glucose lowering within days; full effect 4-8 weeks", "Key advantages: Weight neutral to modest weight loss | No hypoglycemia | Very low cost | CV benefit", ]); // 8. Metformin contraindications twoColSlide( "Metformin - Contraindications & Adverse Effects", [ "eGFR <30 mL/min/1.73m² - CONTRAINDICATED", "eGFR 30-45 - use with caution / reduce dose", "Active hepatic disease or alcohol abuse", "Heart failure: stable mild-moderate CHF now acceptable (current guidelines)", "Iodinated contrast: hold on procedure day + 48 h after", "Metabolic acidosis", ], [ "GI effects (nausea, diarrhea, cramps) - up to 30%; dose-related, usually resolve", "Lactic acidosis - rare (0.03/1000 patient-years); risk highest with renal/hepatic impairment", "Vitamin B12 depletion - check annually in long-term users", "Metallic taste", "NO weight gain, NO hypoglycemia (when used alone)", ], "Contraindications / Cautions", "Adverse Effects" ); // 9. Metformin monitoring contentSlide("Metformin - Monitoring", [ "eGFR at baseline, annually, or more frequently if declining renal function", "Vitamin B12 levels: annually in long-term users (metformin reduces B12 absorption in ileum)", "LFTs at baseline", "HbA1c every 3 months until at target, then every 6 months", "Contrast dye protocol: hold metformin for 48 hours before and after iodinated contrast when eGFR <60", "SICK-DAY RULES (SADMAN): Stop Metformin during vomiting/diarrhea illness - risk of AKI and drug accumulation", ]); // ─── SULFONYLUREAS ──────────────────────────────────────────────────────── addSectionDivider("2. Sulfonylureas (SUs)", C.teal); // 10. SU mechanism contentSlide("Sulfonylureas - Mechanism of Action", [ "Bind to sulfonylurea receptor 1 (SUR1) subunit of pancreatic beta-cell KATP channels", "Channel closure → membrane depolarization → voltage-gated Ca²⁺ channels open → Ca²⁺ influx", "Ca²⁺ influx triggers exocytosis of insulin-containing granules", "Effect is GLUCOSE-INDEPENDENT - insulin secreted even when glucose is low → hypoglycemia risk", "Require FUNCTIONAL beta cells - ineffective in type 1 DM or very late T2DM", "Second generation (glipizide, glyburide, glimepiride) are more potent and selective than first generation", ]); // 11. SU dosing table tableSlide( "Sulfonylureas - Drug Comparison", ["Drug (Brand)", "Starting Dose", "Max Dose", "Duration", "Renal Notes"], [ ["Glipizide (Glucotrol)", "5 mg daily", "40 mg/day", "12-24 h", "Preferred in CKD"], ["Glyburide (DiaBeta)", "2.5-5 mg daily", "20 mg/day", "16-24 h", "AVOID in elderly/CKD"], ["Glimepiride (Amaryl)", "1-2 mg daily", "8 mg/day", "24 h", "Use small doses in CKD"], ["Chlorpropamide (1st gen)", "100-250 mg daily", "500 mg/day", "24-72 h", "Avoid - obsolete"], ["Tolbutamide (1st gen)", "500 mg TID", "3 g/day", "6-12 h", "Short acting"], ], [2.2, 1.8, 1.6, 1.5, 2.3] ); // 12. SU safety twoColSlide( "Sulfonylureas - Key Clinical Points", [ "Potent HbA1c reduction (1-2%)", "Low cost, extensive clinical history", "Take 30 min BEFORE meals", "Glipizide XL - take with breakfast", "Secondary failure: 5-10%/year as beta-cell mass declines", "Sulfonamide allergy: theoretical cross-reactivity (clinical significance unclear)", ], [ "HYPOGLYCEMIA - major risk, especially glyburide", "Weight gain (2-5 kg)", "Glyburide: AVOID in elderly and CKD (active metabolite accumulates)", "Beta-blockers MASK hypoglycemia symptoms (tachycardia suppressed; sweating is preserved)", "Contraindicated: Type 1 DM, severe renal/hepatic impairment", "Discontinue when prandial insulin is added (hypoglycemia risk doubles)", ], "Advantages & Administration", "Risks & Precautions" ); // ─── MEGLITINIDES ──────────────────────────────────────────────────────── addSectionDivider("3. Meglitinides (Glinides)", C.slate); // 13. Meglitinides twoColSlide( "Meglitinides - Mechanism, Dosing & Clinical Notes", [ "MECHANISM: Same target as SUs (SUR1/KATP channels) but different binding site", "Shorter duration of action - designed to cover postprandial glucose spikes", "Repaglinide: 0.5-4 mg before each meal (max 16 mg/day)", "Nateglinide: 60-120 mg before each meal", "KEY RULE: Take with meal; SKIP the dose if a meal is skipped", "More flexible than SUs (meal-by-meal dosing)", ], [ "ADVANTAGES over SUs:", "Lower fasting hypoglycemia risk", "Flexible meal-by-meal dosing", "DISADVANTAGES:", "Dosed 3x/day (adherence burden)", "Expensive, modest HbA1c reduction", "Weight gain", "RENAL NOTE: Repaglinide safer in CKD (biliary excretion); Nateglinide - caution in renal impairment", ], "Mechanism & Dosing", "Clinical Comparison" ); // ─── TZDs ──────────────────────────────────────────────────────────────── addSectionDivider("4. Thiazolidinediones\n(TZDs / Glitazones)", C.navy); // 14. TZD mechanism contentSlide("TZDs - Mechanism of Action", [ "Peroxisome proliferator-activated receptor-gamma (PPARγ) agonists", "PPARγ is a nuclear transcription factor predominantly expressed in adipose tissue", "Activation increases transcription of genes encoding GLUT4, adiponectin, and lipogenic enzymes", "Net effect: redistribution of fat from visceral/ectopic to subcutaneous; improved insulin sensitivity", "Reduce hepatic glucose output and improve peripheral glucose uptake", "Onset of effect: WEEKS TO MONTHS (transcriptional mechanism - not acute)", "Members: Pioglitazone (Actos) - widely available; Rosiglitazone (Avandia) - FDA REMS restriction", ]); // 15. TZD clinical twoColSlide( "TZDs - Advantages & Major Concerns", [ "Durable HbA1c reduction (0.7-1.0%)", "No hypoglycemia when used alone", "Pioglitazone improves lipids: raises HDL, lowers TG", "PROactive trial: pioglitazone may reduce CV events", "Pioglitazone: 15-45 mg once daily", "Rosiglitazone: 2-8 mg daily (restricted)", "May benefit NAFLD/NASH (off-label)", ], [ "Heart failure (NYHA III-IV): ABSOLUTELY contraindicated - TZDs cause fluid retention", "Bladder cancer: pioglitazone - avoid in active/prior bladder cancer", "Bone fractures: increased risk especially in postmenopausal women (reduced bone density)", "Rosiglitazone: increased MI risk (FDA REMS)", "Hepatotoxicity: check LFTs at baseline; monitor periodically", "TZD + insulin: significantly increases fluid retention and HF risk - use with GREAT caution", ], "Advantages", "Major Concerns (Contraindications)" ); // ─── DPP-4 INHIBITORS ──────────────────────────────────────────────────── addSectionDivider("5. DPP-4 Inhibitors\n(Gliptins)", C.teal); // 16. DPP-4 mechanism contentSlide("DPP-4 Inhibitors - Mechanism of Action", [ "DPP-4 (dipeptidyl peptidase-4) is an enzyme that rapidly degrades GLP-1 and GIP (incretin hormones)", "Incretin hormones are secreted by gut in response to food intake", "DPP-4 inhibitors prevent incretin degradation → prolonged GLP-1 and GIP activity", "Elevated GLP-1/GIP → glucose-dependent insulin secretion from beta cells", "Elevated GLP-1/GIP → decreased glucagon from alpha cells (suppresses hepatic glucose output)", "GLUCOSE-DEPENDENT mechanism: only active when glucose is elevated → minimal hypoglycemia risk", "Modest effect on weight (weight neutral)", "Oral once-daily dosing (most members)", ]); // 17. DPP-4 dosing table tableSlide( "DPP-4 Inhibitors - Drug Comparison & Renal Dosing", ["Drug (Brand)", "Standard Dose", "eGFR 30-45", "eGFR <30", "Special Note"], [ ["Sitagliptin (Januvia)", "100 mg once daily", "50 mg once daily", "25 mg once daily", "Dose-adjust in CKD"], ["Saxagliptin (Onglyza)", "5 mg once daily", "2.5 mg once daily", "2.5 mg once daily", "Increased HF risk - caution"], ["Linagliptin (Tradjenta)", "5 mg once daily", "No adjustment", "No adjustment", "Biliary excretion - CKD-safe"], ["Alogliptin (Nesina)", "25 mg once daily", "12.5 mg once daily", "6.25 mg once daily", "Dose-adjust in CKD"], ], [2.2, 2.0, 1.8, 1.8, 1.6] ); // 18. DPP-4 safety contentSlide("DPP-4 Inhibitors - Safety & Adverse Effects", [ "ADVANTAGES: Weight neutral | Low hypoglycemia risk | Well tolerated | Once-daily oral dosing", "Saxagliptin (SAVOR-TIMI trial): INCREASED heart failure hospitalization - use with caution in HF or high HF risk patients", "Possible pancreatitis and pancreatic cancer risk - causality NOT established; remain vigilant, report persistent abdominal pain", "Nasopharyngitis and upper respiratory infections (class effect)", "Arthralgia (joint pain) - class effect", "Bullous pemphigoid (rare skin blistering disease) - FDA class-wide warning; monitor skin", "GLP-1 RA + DPP-4 inhibitor combination: NOT recommended - both target incretin system; DPP-4 inhibitor adds NO benefit when GLP-1 RA is already given", ]); // ─── SGLT2 INHIBITORS ───────────────────────────────────────────────────── addSectionDivider("6. SGLT2 Inhibitors\n(Gliflozins)", C.green); // 19. SGLT2 mechanism contentSlide("SGLT2 Inhibitors - Mechanism of Action", [ "SGLT2 (sodium-glucose cotransporter 2) is located in the proximal renal tubule (S1 segment)", "Normally responsible for ~90% of renal glucose reabsorption", "SGLT2 inhibitors BLOCK this transporter → glucosuria (spill ~70-80 g glucose/day in urine)", "Result: blood glucose reduced; osmotic diuresis (caloric loss)", "Mechanism is INSULIN-INDEPENDENT - effective even with severe insulin deficiency", "ADDITIONAL BENEFITS beyond glucose lowering:", " → Osmotic diuresis reduces preload → hemodynamic benefit in heart failure", " → Blood pressure reduction (3-5 mmHg systolic)", " → Weight loss (1-3 kg)", " → Direct cardiorenal protective effects (not fully explained by glucose lowering alone)", ]); // 20. SGLT2 outcomes tableSlide( "SGLT2 Inhibitors - Key Outcome Trials", ["Drug", "Trial", "Key Finding", "FDA Indication Expanded"], [ ["Empagliflozin (Jardiance)", "EMPA-REG OUTCOME", "Reduced MACE, CV death, HF hospitalization", "Yes - CV & CKD"], ["Canagliflozin (Invokana)", "CANVAS / CREDENCE", "Reduced MACE, HF hosp; CKD progression", "Yes - CV & CKD"], ["Dapagliflozin (Farxiga)", "DECLARE, DAPA-HF, DAPA-CKD", "HFrEF benefit (without DM); CKD benefit", "Yes - HF & CKD (no DM required)"], ["Ertugliflozin (Steglatro)", "VERTIS CV", "CV safety confirmed; no MACE reduction", "Limited"], ], [2.5, 2.3, 3.2, 1.4] ); // 21. SGLT2 adverse effects twoColSlide( "SGLT2 Inhibitors - Adverse Effects & Precautions", [ "Genital mycotic infections (candidiasis) - VERY COMMON, especially in women", "Urinary tract infections (less clearly established than genital infections)", "Volume depletion / hypotension - especially with diuretics or in elderly", "Euglycemic DKA: glucose may be only mildly elevated (150-200 mg/dL); check ketones if nausea/vomiting on SGLT2", "Fournier's gangrene (necrotizing fasciitis of genitalia) - rare class warning", ], [ "Amputations: canagliflozin - increased risk (Charcot foot, PAD patients - caution)", "Bone fractures: canagliflozin associated", "Hold SGLT2 inhibitors perioperatively (48 hours before surgery) - DKA risk", "SADMAN sick-day rules: stop SGLT2 inhibitors during vomiting/diarrhea illness", "Require eGFR ≥30-45 for glycemic benefit; cardiorenal benefit may extend to lower eGFR", "Counsel on genital hygiene", ], "Common Side Effects", "Serious Risks & Perioperative" ); // ─── ALPHA-GLUCOSIDASE INHIBITORS ───────────────────────────────────────── addSectionDivider("7. Alpha-Glucosidase\nInhibitors", C.slate); // 22. AGI contentSlide("Alpha-Glucosidase Inhibitors - Acarbose & Miglitol", [ "MECHANISM: Competitively inhibit intestinal brush border alpha-glucosidase enzymes", " → Delayed digestion of complex carbohydrates and disaccharides", " → Blunted postprandial glucose rise (targets postprandial hyperglycemia specifically)", " → Act LOCALLY in gut; acarbose has minimal systemic absorption", "DOSING: Acarbose 25-100 mg WITH each meal (titrate slowly); Miglitol 25-100 mg with meals", "ADVANTAGES: No hypoglycemia (alone) | No systemic absorption (acarbose) | Modest weight benefit", "DISADVANTAGES: GI side effects (flatulence, diarrhea, bloating) in ~50-70% - often limits use | Modest HbA1c reduction (~0.5-0.8%) | Three times daily dosing", "CRITICAL CAVEAT: If hypoglycemia occurs while on acarbose + SU or insulin - treat with PURE GLUCOSE (dextrose) NOT sucrose/orange juice (acarbose blocks sucrose digestion!)", ]); // ─── OTHER AGENTS ───────────────────────────────────────────────────────── addSectionDivider("8. Other Agents", C.navy); // 23. Other agents twoColSlide( "Bile Acid Sequestrants & Dopamine Agonists", [ "Drug: Colesevelam (Welchol)", "Class: Bile acid sequestrant", "Mechanism: Unknown in DM; modestly reduces HbA1c (~0.5%); also lowers LDL-C", "USE CASE: When glycemic + lipid management needed simultaneously", "Adverse effects: GI side effects; reduces absorption of fat-soluble vitamins and some drugs (timing matters)", "Advantage: Not absorbed systemically", ], [ "Drug: Bromocriptine (Cycloset)", "Class: Dopamine D2 agonist (CNS-acting)", "Mechanism: Resets hypothalamic circadian rhythms → improves insulin sensitivity", "Modest HbA1c reduction", "May be continued when insulin is added", "Adverse effects: Nausea, orthostatic hypotension, dizziness, fatigue", "FDA approved for T2DM (Cycloset formulation only)", ], "Colesevelam", "Bromocriptine" ); // ─── TREATMENT ALGORITHM ───────────────────────────────────────────────── addSectionDivider("Treatment Escalation\nAlgorithm", C.teal); // 24. First-line contentSlide("First-Line & Escalation Steps (ADA/EASD Consensus)", [ "FIRST LINE: Metformin remains recommended first-line if tolerated (unless contraindicated)", "EARLY CONSIDERATION: If HbA1c ≥9% at presentation → initiate dual therapy from start OR insulin directly", "Individualized early first-line based on comorbidities (see next slide)", "STEP 1: Monotherapy (metformin or preferred first-line agent based on comorbidities)", "STEP 2: Dual therapy at 3 months if HbA1c not at goal (add agent from different class)", "STEP 3: Triple therapy at 3 months if still not at goal", "STEP 4: Injectable therapy - GLP-1 RA BEFORE basal insulin", "STEP 5: Basal insulin + bolus insulin (full basal-bolus) if needed", "Reassess every 3 months until targets are achieved", ]); // 25. Preferred agents by clinical context table tableSlide( "Drug Selection by Clinical Context", ["Clinical Scenario", "Preferred Agent(s)", "Avoid"], [ ["Established ASCVD or high CV risk", "GLP-1 RA (liraglutide, semaglutide, dulaglutide); SGLT2 inhibitor", "TZDs if HF risk"], ["Heart failure (HFrEF)", "SGLT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin)", "TZDs, saxagliptin"], ["CKD (eGFR 25-60, albuminuria)", "SGLT2 inhibitor; Linagliptin (DPP-4, no dose adj)", "Metformin if eGFR <30, Glyburide"], ["Weight loss priority", "GLP-1 RA (most weight loss), SGLT2 inhibitor", "TZDs, SUs"], ["Minimizing hypoglycemia", "DPP-4 inhibitor, GLP-1 RA, SGLT2 inhibitor, TZD", "SUs, Meglitinides"], ["Cost concern", "Metformin, Sulfonylurea, TZD (pioglitazone)", "GLP-1 RA, SGLT2 inhibitors"], ["Elderly (>65 years)", "DPP-4 inhibitors (well tolerated)", "Glyburide (prolonged hypoglycemia)"], ["Obesity", "GLP-1 RA, SGLT2 inhibitor", "TZDs, SUs"], ], [2.5, 4.0, 2.9] ); // 26. Individualization contentSlide("Individualization of Therapy - Special Populations", [ "Elderly (>65 yr): Avoid glyburide; target HbA1c 7.5-8.5% based on frailty; DPP-4 inhibitors well tolerated", "CKD stage 3b-5: Avoid metformin (eGFR <30); avoid SUs except glipizide/small dose glimepiride; SGLT2 inhibitors lose glycemic efficacy at eGFR <45 but retain cardiorenal benefit; linagliptin preferred DPP-4 (no dose adjustment)", "Heart failure: Avoid TZDs; prefer SGLT2 inhibitors; avoid saxagliptin", "ASCVD: GLP-1 RA or SGLT2 inhibitor as early add-on", "Liver disease: Avoid metformin (severe hepatic impairment); avoid TZDs; SUs unpredictable; DPP-4 inhibitors generally safe", "Pregnancy: Insulin is PREFERRED; metformin and glyburide used but cross placenta; ALL SGLT2/DPP-4/GLP-1 agents - AVOID", "Low adherence: Long-acting, once-daily or once-weekly agents (semaglutide weekly, dulaglutide weekly)", "Hypoglycemia history: Avoid SUs and meglitinides; prefer GLP-1 RA, SGLT2 inhibitors, DPP-4 inhibitors, TZDs", ]); // ─── HBA1C TARGETS ──────────────────────────────────────────────────────── addSectionDivider("HbA1c Targets &\nMonitoring", C.navy); // 27. HbA1c targets tableSlide( "HbA1c Targets - Individualized Goals", ["Patient Population", "HbA1c Target", "Rationale"], [ ["Most non-elderly adults", "<7.0%", "Reduces microvascular complications"], ["Short disease duration, no CVD, long life expectancy", "<6.5%", "Tight control if achievable without hypoglycemia"], ["Elderly, limited life expectancy, hypoglycemia unawareness, multiple comorbidities", "7.5-8.5% (or <9%)", "Prevent hypoglycemia > tight control"], ["Pregnant (2nd-3rd trimester)", "<6.0-6.5%", "Prevent fetal macrosomia and complications"], ], [3.0, 2.2, 4.8] ); // 28. Monitoring schedule tableSlide( "Comprehensive Monitoring Schedule", ["Parameter", "Frequency", "Notes"], [ ["HbA1c", "Every 3 months until at goal; then every 6 months", "Primary glycemic target"], ["Fasting blood glucose (SMBG)", "Daily to weekly depending on regimen", "More frequent if on SU or insulin"], ["eGFR / Serum creatinine", "Baseline, then annually (or more with declining function)", "Critical for dose adjustments"], ["Urine albumin-to-creatinine ratio", "Annually", "Early CKD detection"], ["Lipid panel", "Annually", "Part of CV risk management"], ["Liver function tests", "Baseline for TZDs; periodically", "Especially for TZDs"], ["Vitamin B12", "Annually in patients on long-term metformin", "Ileal absorption reduced by metformin"], ["Blood pressure", "Every visit", "CV risk factor"], ["Foot examination", "Annually", "Peripheral neuropathy/PAD screening"], ["Retinal screening", "At diagnosis (T2DM), then annually or biannually", "Diabetic retinopathy detection"], ], [2.3, 3.5, 3.6] ); // ─── CLINICAL CAVEATS ───────────────────────────────────────────────────── addSectionDivider("Critical Clinical\nCaveats", C.red); // 29. Key caveats 1 warningSlide("High-Yield Clinical Caveats (1-6)", [ "Metformin + contrast: Hold for 48 h before AND after iodinated contrast when eGFR <60 (risk: contrast nephropathy → metformin accumulation → lactic acidosis)", "Euglycemic DKA with SGLT2 inhibitors: Glucose may be only 150-200 mg/dL - normal glucose does NOT rule out DKA. Check ketones if patient on SGLT2i presents with nausea/vomiting/malaise. Hold perioperatively (48 h before surgery).", "SADMAN sick-day rule: Stop Metformin, ACEi, Diuretics, NSAIDs, and SGLT2 inhibitors during vomiting/diarrhea illness to prevent AKI and drug accumulation.", "Beta-blockers mask hypoglycemia symptoms (tachycardia and tremor suppressed). SWEATING IS PRESERVED and is the main warning sign to counsel patients on.", "Hypoglycemia on acarbose: MUST treat with pure glucose (dextrose tablets, IV glucose, glucagon) - NOT orange juice or sucrose (acarbose blocks sucrose hydrolysis).", "Sulfonylurea secondary failure: SU efficacy declines 5-10%/year as beta-cell mass decreases. Do not keep escalating dose. Switch strategy.", ]); // 30. Key caveats 2 warningSlide("High-Yield Clinical Caveats (7-12)", [ "GLP-1 RA and pancreatitis: Contraindicated with history of pancreatitis, medullary thyroid carcinoma (MTC), or MEN2. Advise patients to report persistent abdominal pain.", "TZD + insulin combination: Increases fluid retention and HF risk significantly. Avoid or use with great caution.", "When adding insulin: Discontinue SUs and meglitinides when prandial insulin is added (hypoglycemia risk). Metformin, DPP-4i, SGLT2i, and GLP-1 RA can generally be continued.", "CVOTs summary: DPP-4 inhibitors - CV safety confirmed but no benefit. GLP-1 RAs (liraglutide, semaglutide, dulaglutide) and SGLT2 inhibitors showed MACE reduction. SGLT2i showed strongest HF hospitalization reduction.", "GLP-1 RA + DPP-4 inhibitor: NOT recommended - both target incretin system; DPP-4i adds no benefit when GLP-1 RA already given.", "Renal function armamentarium: As eGFR falls: Linagliptin (no renal dose adj) | Repaglinide safer than SUs in CKD | SGLT2i lose glycemic efficacy at eGFR <45 (cardiorenal benefit extends lower) | Insulin effective at all eGFR levels but hypoglycemia risk rises.", ]); // 31. Drug comparison (advantages/disadvantages summary) highlightBoxSlide( "Class-by-Class Summary: Advantage vs. Concern", null, [ { label: "Metformin", value: "✓ CV benefit\n✓ Weight neutral\n✓ Low cost\n✓ No hypoglycemia\n\n⚠ eGFR <30\n⚠ GI side effects\n⚠ B12 depletion", color: C.navy, }, { label: "Sulfonylureas", value: "✓ Potent (1-2% HbA1c)\n✓ Low cost\n\n⚠ HYPOGLYCEMIA\n⚠ Weight gain\n⚠ Secondary failure\n⚠ Avoid glyburide in elderly/CKD", color: C.teal, }, { label: "TZDs", value: "✓ Durable effect\n✓ Lipid benefit\n✓ No hypoglycemia\n\n⚠ HF risk\n⚠ Fluid retention\n⚠ Fractures\n⚠ Bladder cancer (pio)", color: C.slate, }, { label: "DPP-4i", value: "✓ Well tolerated\n✓ Weight neutral\n✓ Glucose-dependent\n\n⚠ Saxagliptin & HF\n⚠ Bullous pemphigoid\n⚠ Pancreatitis risk", color: "1A5276", }, ] ); // 32. SGLT2 vs GLP-1 RA highlights twoColSlide( "SGLT2 Inhibitors vs GLP-1 RAs - Head-to-Head", [ "Route: ORAL once daily", "Mechanism: Renal glucose excretion", "CV benefit: MACE reduction + strong HF benefit", "HF hospitalization: Best in class", "CKD benefit: Strong (CREDENCE, DAPA-CKD)", "Weight loss: 1-3 kg", "BP reduction: Yes (osmotic diuresis)", "Hypoglycemia: No", "Key risk: Genital infections, euglycemic DKA", "Cost: High", ], [ "Route: SUBCUTANEOUS injection (most) or oral semaglutide", "Mechanism: Incretin receptor agonist (GLP-1R)", "CV benefit: MACE reduction + atherosclerosis benefit", "HF hospitalization: Less pronounced than SGLT2i", "GI effects: Significant nausea, vomiting", "Weight loss: 3-5 kg (semaglutide > 5 kg)", "BP reduction: Modest", "Hypoglycemia: No", "Key risk: Pancreatitis, MTC history contraindication", "Cost: Very high", ], "SGLT2 Inhibitors", "GLP-1 Receptor Agonists" ); // 33. Exam high-yield summary contentSlide("Exam High-Yield: Quick-Fire Review", [ "First-line T2DM drug: Metformin (unless contraindicated)", "Safest DPP-4 inhibitor in CKD: Linagliptin (no renal dose adjustment)", "Safest meglitinide in CKD: Repaglinide (biliary excretion)", "Avoid in elderly/CKD: Glyburide (prolonged hypoglycemia from active metabolite)", "Contraindicated in HF: TZDs (fluid retention worsens HF)", "Euglycemic DKA risk: SGLT2 inhibitors (hold perioperatively)", "Hypoglycemia treatment on acarbose: Dextrose/glucose ONLY - not sucrose", "GLP-1 RA + DPP-4i: Do NOT combine (no added incretin benefit)", "Best agent for HFrEF: SGLT2 inhibitor (empagliflozin or dapagliflozin)", "Hold before contrast: Metformin (48 h if eGFR <60)", "Annual B12 monitoring: Long-term metformin users", "Beta-blocker + SU: Masks hypoglycemia symptoms; sweating preserved", ]); // 34. Closing slide { const s = pres.addSlide(); s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: "100%", h: "100%", fill: { color: C.navy } }); s.addShape(pres.ShapeType.rect, { x: 0, y: 2.2, w: "100%", h: 0.08, fill: { color: C.gold } }); s.addShape(pres.ShapeType.rect, { x: 0, y: 3.4, w: "100%", h: 0.08, fill: { color: C.teal } }); s.addText("Oral Hypoglycemic Agents", { x: 0.5, y: 0.5, w: 9, h: 1.5, fontSize: 34, bold: true, color: C.white, fontFace: "Calibri", align: "center", valign: "middle", }); s.addText("Complete Clinical Pharmacology Reference", { x: 0.5, y: 2.4, w: 9, h: 0.8, fontSize: 18, color: C.gold, fontFace: "Calibri", align: "center", italic: true, }); s.addText("Sources: Lippincott Illustrated Reviews: Pharmacology 7th Ed.\nWashington Manual of Medical Therapeutics | Goldman-Cecil Medicine\nTextbook of Family Medicine 9th Ed. | Comprehensive Clinical Nephrology 7th Ed.", { x: 0.5, y: 3.6, w: 9, h: 1.4, fontSize: 13, color: C.teal, fontFace: "Calibri", align: "center", }); s.addText("For educational use | Medical & Pharmacy Students", { x: 0.5, y: 5.1, w: 9, h: 0.35, fontSize: 11, color: "888888", fontFace: "Calibri", align: "center", }); } // ─── WRITE FILE ──────────────────────────────────────────────────────────── pres.writeFile({ fileName: "/home/daytona/workspace/oral-hypoglycemics-pptx/Oral_Hypoglycemic_Agents.pptx" }) .then(() => console.log("SUCCESS: /home/daytona/workspace/oral-hypoglycemics-pptx/Oral_Hypoglycemic_Agents.pptx")) .catch(e => { console.error("ERROR:", e); process.exit(1); });