Endocrine & Metabolic
Type 2 Diabetes Mellitus
GoalLower fasting/postprandial glucose, prevent microvascular and atherosclerotic complications, and — when possible — reverse the underlying insulin resistance.
Conventional / Rx
Metforminfirst-line
Strong- Mechanism
- Activates hepatic AMPK → suppresses gluconeogenesis; sensitises peripheral insulin signalling.
- Dose
- 500 mg PO BID with meals; titrate to 1 g BID (max 2 g/day).
- Watch
- Lactic acidosis if estimated glomerular filtration rate <30; GI side effects in first 2 weeks.
glucagon-like peptide-1 RA (semaglutide, liraglutide)first-line
Strong- Mechanism
- Mimics native glucagon-like peptide-1 → glucose-dependent insulin release + delayed gastric emptying + appetite suppression.
- Dose
- Semaglutide 0.25 mg SC weekly × 4 wk → 0.5 mg → up to 2 mg.
- Watch
- Pancreatitis risk; contraindicated in personal/family MTC or MEN-2.
sodium-glucose cotransporter 2 inhibitors (empagliflozin, dapagliflozin)first-line
Strong- Mechanism
- Blocks proximal-tubule glucose reabsorption → glucosuria + natriuresis. Independent CV/renal benefit.
- Dose
- Empagliflozin 10 mg PO daily; ↑ to 25 mg.
- Watch
- Euglycaemic diabetic ketoacidosis; genital mycotic infections; volume depletion.
Basal insulin (glargine, degludec)
Strong- Mechanism
- Replaces deficient endogenous insulin; suppresses overnight hepatic glucose output.
- Dose
- Start 0.1–0.2 U/kg SC at bedtime; titrate +2 U every 3 days until FBG <130.
- Watch
- Hypoglycaemia (especially with sulfonylureas); weight gain.
dipeptidyl peptidase-4 inhibitors (sitagliptin)
Moderate- Mechanism
- Prolongs endogenous glucagon-like peptide-1 half-life by inhibiting its degradation.
- Dose
- Sitagliptin 100 mg PO daily; reduce in chronic kidney disease.
- Watch
- Joint pain; rare bullous pemphigoid. Weight-neutral, no hypoglycaemia.
Natural / Lifestyle
Berberine
Moderate- Mechanism
- AMPK activator (similar pathway to metformin); modulates gut microbiome.
- Dose
- 500 mg PO TID with meals.
- Watch
- GI upset; CYP3A4 inhibition — increases drug levels of statins, cyclosporine.
Bitter melon (Momordica charantia)
Limited- Mechanism
- Contains charantin and polypeptide-P with insulin-mimetic activity.
- Dose
- 50–100 mL fresh juice daily, or 500 mg standardised extract TID.
- Watch
- Hypoglycaemia when combined with insulin/sulfonylureas; avoid in pregnancy.
Cinnamon (Cassia)
Mixed- Mechanism
- MHCP enhances insulin receptor phosphorylation; small ↓ in hemoglobin hemoglobin hemoglobin A1c (~0.3%).
- Dose
- 1–6 g/day standardised.
- Watch
- Coumarin content (Cassia >> Ceylon) — hepatotoxicity at high doses.
Ginseng (Korean, American)
Limited- Mechanism
- Ginsenosides modulate insulin secretion and peripheral sensitivity.
- Dose
- 1–3 g PO daily.
- Watch
- Stimulant effects; interacts with warfarin.
Fenugreek seeds
Limited- Mechanism
- Soluble fibre delays carbohydrate absorption; trigonelline ↑ insulin sensitivity.
- Dose
- 5–10 g powdered seed with meals.
- Watch
- Bleeding risk; lowers thyroid hormone absorption — separate dosing.
Side-by-side — evidence × effect × cost × time to effect
| Option | Evidence | Effect | Cost (estimated) | Time to effect | Resources |
|---|---|---|---|---|---|
Metformin conventional· first-line | Strong | Strong | ~$4 – $30/mo (generic) | 2–4 weeks | |
glucagon-like peptide-1 RA (semaglutide, liraglutide) conventional· first-line | Strong | Strong | ~$900 – $1,400/mo (list) | 2–4 weeks | |
sodium-glucose cotransporter 2 inhibitors (empagliflozin, dapagliflozin) conventional· first-line | Strong | Strong | ~$900 – $1,400/mo (list) | 2–4 weeks | |
Basal insulin (glargine, degludec) conventional | Strong | Moderate-strong | ~$35 – $300/mo | 2–4 weeks | |
dipeptidyl peptidase-4 inhibitors (sitagliptin) conventional | Moderate | Moderate | ~$4 – $30/mo (generic) | 2–4 weeks | |
Berberine natural | Moderate | Moderate | ~$8 – $40/mo | 4–8 weeks | |
Bitter melon (Momordica charantia) natural | Limited | Mild | ~$8 – $40/mo | 2–4 weeks | |
Cinnamon (Cassia) natural | Mixed | Moderate | ~$4 – $30/mo (generic) | 2–4 weeks | |
Ginseng (Korean, American) natural | Limited | Mild | ~$4 – $30/mo (generic) | 2–4 weeks | |
Fenugreek seeds natural | Limited | Mild | ~$4 – $30/mo (generic) | 2–4 weeks |
Cost is a typical U.S. adult outpatient estimate and varies by insurance, region, and product quality — confirm with GoodRx or your pharmacy. Time-to-effect and effect strength are derived from the option's evidence label and first-line status; the per-card detail below has the authored mechanism, dose, and watch-for notes. Resource links point to NIH, FDA, NCCIH, CDC, GoodRx, and peer society pages — never to commercial retailers.
When this framework fails — escalate
- ▸diabetic ketoacidosis (Kussmaul breathing, fruity breath, anion gap >12) — emergency department now.
- ▸hyperosmolar hyperglycemic state (glucose >600, osmolality >320, altered mentation) — intensive care unit.
- ▸New-onset diabetic foot ulcer with crepitus or systemic signs — surgical eval.
- ▸Pregnancy with hemoglobin hemoglobin hemoglobin A1c >6.5% — switch to insulin + maternal-fetal medicine referral.
Bedside pearls
- ·Metformin + glucagon-like peptide-1 + sodium-glucose cotransporter 2 is the modern 'cardiometabolic triple' for patients with ASCVD, chronic kidney disease, or heart failure with reduced ejection fraction.
- ·Berberine and metformin share AMPK — don't double-stack without monitoring.
- ·Patients on sodium-glucose cotransporter 2 inhibitors can develop diabetic ketoacidosis at near-normal glucose — check anion gap if vomiting.