Insulin Sensitivity

Scheduling, administration, biomarkers, and practical guidance.

Tirzepatide titration (FDA-approved)

2.5 mg SC once weekly × 4 weeks, then step up by 2.5 mg every 4 weeks

Target maintenance 5–15 mg weekly. 'Well-tolerated' before stepping up means resolved GI symptoms, not just reduced. Prescriber-supervised only.

Semaglutide titration (FDA-approved)

0.25 mg SC once weekly × 4 weeks, then step up

Step up at 4-week intervals (0.5, 1.0, 1.7, 2.4 mg) as GI tolerance allows. Target maintenance 1.0–2.4 mg weekly for weight/insulin indications; lower for diabetes-only use.

Oral semaglutide (Rybelsus)

Take first thing in the morning with ≤4 oz water; 30-min fast afterwards

Absorption is fasting-dependent. Any food or other medication within 30 minutes significantly degrades bioavailability.

Retatrutide (investigational)

Per clinical trial protocol — not outpatient

Phase 3 ongoing at time of writing. No standardised outpatient schedule exists; do not extrapolate trial doses to self-administration.

Tesamorelin (HIV lipodystrophy indication)

2 mg SC once daily

Approved only for HIV-associated lipodystrophy. Not indicated for general insulin sensitisation. Daily injection at consistent time.

MOTS-c (investigational — research only)

Phase 1a/1b dosing only within clinical trials

No established outpatient dose. Grey-market dosing advice is not evidence-based and the compound is not approved for any indication.

Khavinson bioregulators (Pancragen, etc.)

10–20 day pulses, repeated 1–3× per year (per Russian literature)

Pulse protocol differs from chronic daily therapy. Western clinical replication is limited — treat as investigational, clinician-supervised only.

Pre-anaesthesia discontinuation

Pause weekly incretin agents at least 1 week before elective procedures

Current anaesthesia guidance — regurgitation and aspiration risk from delayed gastric emptying is the documented concern. Disclose peptide use to every anaesthetist.