Insulin Types
| Type | Examples | Onset | Peak | Duration | Use |
|---|
| Rapid-acting | Lispro (Humalog), Aspart (NovoLog), Glulisine (Apidra) | 15 min | 1–2 hr | 3–5 hr | Mealtime (bolus); give within 15 min of meal |
| Short-acting (regular) | Regular insulin (Humulin R, Novolin R) | 30–60 min | 2–4 hr | 5–8 hr | Mealtime; IV insulin drips (DKA); give 30 min before meal |
| Intermediate-acting | NPH (Humulin N, Novolin N) | 1–3 hr | 4–12 hr | 12–18 hr | Twice-daily basal coverage; less used now |
| Long-acting (basal) | Glargine (Lantus, Basaglar, Toujeo), Detemir (Levemir) | 1–4 hr | Peakless (glargine) / 6–8 hr (detemir) | 20–24 hr (glargine); 16–20 hr (detemir) | Once-daily basal insulin; no mixing with other insulins (glargine) |
| Ultra-long-acting | Degludec (Tresiba) | 1–2 hr | Peakless | >42 hr | Once daily; lowest hypoglycemia risk; flexible dosing timing |
| Premixed | 70/30 (NPH/Regular), 75/25 (lispro protamine/lispro) | Variable | Variable | Variable | Twice-daily; less flexible; less preferred for tight control |
🧠 Mnemonic — Insulin Onset: RINSRapid (15 min) → Short/Regular (30–60 min) → Intermediate/NPH (1–3 hr) → Basal/long-acting (1–4 hr, no peak)
🎯 Boards PearlBasal-bolus regimen = long-acting (basal) once daily + rapid-acting (bolus) with each meal — physiologic and preferred for T1DM and intensive T2DM management. In DKA: use REGULAR insulin IV infusion (NOT rapid-acting analogs). Do NOT start insulin if K+ <3.3 mEq/L — repleat potassium first (insulin drives K+ into cells → fatal hypokalemia). Storage: unopened insulin refrigerated; opened vials at room temp up to 28–30 days.
GLP-1 Receptor Agonists
| Drug | Route/Frequency | Key Benefits | Adverse Effects |
|---|
| Semaglutide (Ozempic — weekly SQ; Rybelsus — daily PO; Wegovy — weekly SQ for obesity) | SQ weekly or PO daily | SUSTAIN trials: CV mortality benefit; greatest weight loss (>10–15% with Wegovy); HbA1c reduction 1.5–2% | N/V (25–45%); delayed gastric emptying; avoid in MEN 2, personal/family history of medullary thyroid cancer; pancreatitis (rare) |
| Liraglutide (Victoza — T2DM; Saxenda — obesity) | SQ daily | LEADER trial: reduces CV mortality, MI, stroke in T2DM with CVD; modest weight loss (~3kg); HbA1c reduction 1–1.5% | Same class effects as semaglutide; Saxenda approved for weight loss |
| Dulaglutide (Trulicity) | SQ weekly | REWIND trial: CV benefit; HbA1c reduction 1–1.5%; easy once-weekly pen device | Class effects |
| Exenatide (Byetta — BID; Bydureon — weekly) | SQ BID or weekly | First approved GLP-1 RA; weight loss benefit; no proven CV mortality benefit (EXSCEL trial neutral) | Class effects; injection site reactions (Bydureon) |
🏥 When to Choose GLP-1 AgonistADA/ACC guidelines: add GLP-1 agonist when HbA1c not at goal on metformin AND patient has: CVD (proven benefit: semaglutide, liraglutide, dulaglutide), or needs weight loss, or wants to avoid hypoglycemia. Contraindication: personal or family history of medullary thyroid carcinoma (MTC) or MEN 2 syndrome (black box warning — rodent thyroid C-cell tumors). Start at low dose and titrate slowly to reduce GI side effects.
SGLT-2 Inhibitors (Gliflozins)
| Drug | Trial / Key Benefit | HF Benefit | Renal Benefit |
|---|
| Empagliflozin (Jardiance) | EMPA-REG OUTCOME: 38% CV death reduction; 35% HHF reduction | Yes (HFrEF + HFpEF) | Yes (EMPA-KIDNEY trial) |
| Canagliflozin (Invokana) | CANVAS: CV benefit; CREDENCE: renal protection in T2DM + CKD | Yes | Yes — FDA approved for DKD |
| Dapagliflozin (Farxiga) | DECLARE-TIMI 58: HHF reduction; DAPA-HF: HFrEF mortality benefit (non-diabetic too); DAPA-CKD | Yes (HFrEF + HFpEF) | Yes — CKD indication |
Mechanism & Side Effects
Block SGLT-2 in proximal tubule → inhibit glucose reabsorption → glycosuria → blood glucose reduction. Also reduce sodium reabsorption → osmotic diuresis → weight loss, BP reduction; reduce glomerular hyperfiltration (renoprotection); reduce preload/afterload (HF benefit).
🎯 Boards Pearl — SGLT-2 Adverse EffectsGenital mycotic infections (most common — vulvovaginal candidiasis, balanitis; yeast loves glucose). UTI risk increased. Volume depletion/hypotension. DKA (euglycemic DKA — BG may not be dramatically elevated — hold before surgery, fasting states, illness). Fournier's gangrene (necrotizing fasciitis of genitalia — rare). Canagliflozin: lower limb amputations (CANVAS trial) — use caution in PAD. Hold 3–7 days before major surgery. Hold when eGFR <20–30 (drug-specific thresholds).
DPP-4 Inhibitors (Gliptins)
| Drug | Dose | CV Safety | Notes |
|---|
| Sitagliptin (Januvia) | 100mg daily (reduce to 50mg if eGFR 30–50; 25mg if <30) | CV neutral (TECOS) | Well-tolerated; no weight change; no hypoglycemia; risk of pancreatitis (rare); saxagliptin increases HHF |
| Saxagliptin (Onglyza) | 5mg daily | Increased HHF (SAVOR-TIMI) | Avoid in HF patients; otherwise well-tolerated |
| Linagliptin (Tradjenta) | 5mg daily — no renal dose adjustment needed | CV neutral (CAROLINA) | Excreted biliary — safe in all stages of CKD without dose adjustment; preferred in CKD |
| Alogliptin (Nesina) | 25mg daily | CV neutral (EXAMINE) | Reduce dose in renal impairment |
Sulfonylureas & Meglitinides
| Drug | Mechanism | Examples | Key Concerns |
|---|
| Sulfonylureas | Stimulate pancreatic beta cells to secrete insulin by blocking ATP-sensitive K+ channels → depolarization → insulin release. Insulin-secretagogues (glucose-independent) | Glipizide, glimepiride, glyburide (1st gen: chlorpropamide, tolbutamide) | HYPOGLYCEMIA risk (especially glyburide — long-acting; avoid in elderly, renal impairment); weight gain (~2kg); avoid in G6PD (hemolytic anemia). Glipizide preferred in elderly (shorter-acting) |
| Meglitinides | Same mechanism as SUs; faster onset and shorter duration — taken with meals only | Repaglinide (Prandin), nateglinide (Starlix) | Less hypoglycemia risk vs. SUs (only take if eating); flexible mealtime dosing; useful for irregular meal schedules; expensive |
Other Antidiabetic Agents
| Drug Class | Examples | Mechanism | Notes |
|---|
| Thiazolidinediones (TZDs) | Pioglitazone (Actos), rosiglitazone (Avandia) | PPAR-γ agonist → improves insulin sensitivity in adipose and muscle | Weight gain (+2–4kg); fluid retention → HF exacerbation (contraindicated in NYHA III–IV HF); pioglitazone → bladder cancer risk; fracture risk. Pioglitazone has NASH benefit (off-label) |
| Alpha-glucosidase inhibitors | Acarbose (Precose), miglitol | Inhibit intestinal alpha-glucosidase → slow carbohydrate digestion → reduce postprandial glucose rise | Modest A1c reduction (~0.5–1%); GI side effects (flatulence, diarrhea) limit use; take with first bite of meal |
| Amylin analogue | Pramlintide (SymlinPen) | Amylin analogue → reduces glucagon secretion, slows gastric emptying, promotes satiety | Used with insulin in T1DM and T2DM; reduces postprandial glucose; weight loss; must reduce pre-meal insulin dose to avoid hypoglycemia |
| Colesevelam (Welchol) | Bile acid sequestrant | Reduces glucose through unknown mechanism (possibly reduced glucose absorption) | Modest A1c reduction (~0.5%); also lowers LDL; GI side effects; many drug interactions |
Pancreatic Enzyme Replacement Therapy (PERT)
| Feature | Detail |
|---|
| Indication | Exocrine pancreatic insufficiency (EPI) from chronic pancreatitis, pancreatic cancer, CF, post-Whipple; when >90% exocrine function lost → steatorrhea, malabsorption |
| Drugs | Pancrelipase (Creon, Pancreaze, Zenpep, Viokace) — contains lipase, amylase, protease derived from porcine pancreas |
| Dosing | Based on LIPASE units: 500–2500 lipase units/kg/meal (max 10,000 lipase units/kg/day). Typical: 40,000–50,000 lipase units with meals; half dose with snacks. Take WITH or IMMEDIATELY before meals |
| Monitoring | Assess steatorrhea (frequency, consistency of stools, weight gain). Monitor fat-soluble vitamin levels (A, D, E, K) |
| Key Points | Enteric-coated formulations (delayed release) protect enzymes from gastric acid. Take with food — pH of duodenum activates enzymes. Add PPI if inadequate response (raises duodenal pH → better enzyme activation). Do NOT chew or crush beads. Pork allergy → use Viokace (non-enteric-coated; add PPI) |
🎯 Boards PearlFat-soluble vitamin supplementation (A, D, E, K) is essential in EPI. Assess response by improved steatorrhea and weight gain — not by lipase levels. Creon is the most commonly prescribed PERT. CF patients require PERT due to mucus obstruction of pancreatic ducts. Adequate PERT reduces malnutrition, improves quality of life, and reduces risk of diabetes and osteoporosis in chronic pancreatitis.