When the panel changed the prescription.
Anonymized cases written for prescribing clinicians. Each case shows the initial plan, the PGx or biomarker finding that changed the decision, and the actual outcome. CME-style; not patient marketing.
GLP-1 non-responder rescued by GIP-arm escalation
42-year-old female, BMI 34, T2D HbA1c 7.6. Six months on semaglutide 1.0 mg with only 3.2% weight loss and continued post-prandial glucose excursions. No AEs.
Escalate semaglutide to 2.0 mg.
GLP1R rs6923761 G/G (reduced response). GIPR rs1800437 wild-type (normal GIP signaling).
Postprandial GIP response intact; GLP-1 surrogate markers blunted.
Switched to tirzepatide 5 mg → 7.5 mg → 10 mg over 12 weeks instead of escalating semaglutide.
11.4% weight loss at 16 weeks, HbA1c 6.4. No additional GI burden vs prior semaglutide.
GLP-1R-reduced responders may benefit more from a dual agonist than from pushing GLP-1 mono to maximum — even when tolerance allows the higher dose.
SSRI co-medication and CYP2D6 poor metabolizer
38-year-old male on paroxetine 30 mg and tramadol PRN, considering peptide therapy for body composition.
Standard CJC-1295 / ipamorelin combination, weekly check-in.
CYP2D6 *4/*4 — poor metabolizer phenotype.
Baseline IGF-1 130 ng/mL (mid-reference for age).
Held peptide initiation pending psychiatry consult to switch SSRI to one with lower CYP2D6 dependence and to clarify tramadol risk. Restarted ipamorelin only after medication change.
No serotonergic event; IGF-1 rose to 198 ng/mL at month 4 with subjective recovery improvement.
Pharmacogenomics changes the order of operations — sometimes the right intervention is to fix the existing drug regimen first, not to add a new one.
MC4R loss-of-function carrier referred out
29-year-old female with hyperphagia since childhood, BMI 41, multiple failed weight-loss attempts including a prior GLP-1 trial that produced only 4% loss.
Tirzepatide initiation with PGx panel.
MC4R heterozygous loss-of-function variant detected.
Leptin elevated; insulin moderately elevated; thyroid normal.
Referred to obesity-medicine specialist with setmelanotide access (FDA-approved for MC4R-pathway monogenic obesity).
Patient initiated setmelanotide; ~9% loss at 6 months and significant hyperphagia reduction.
A small fraction of patients have a single-gene cause of obesity that GLP-1s do not address well. Detecting it routes them to a more appropriate therapy that the patient might never have been offered.
BPC-157 request declined despite patient enthusiasm
34-year-old male athlete requesting BPC-157 for chronic patellar tendinopathy after reading social media protocols.
Patient requested BPC-157 8-week protocol.
Not assessed — case declined before genomic workup.
Imaging confirmed chronic mid-substance tendinopathy; eccentric loading not yet trialed adequately.
Declined to prescribe BPC-157 given (a) no completed Phase II in humans, (b) untested grey-market supply chain, and (c) unexhausted first-line non-pharmacologic options.
Patient enrolled in supervised eccentric loading + isometric protocol; resolved at 14 weeks.
Saying no is part of the protocol. Where the human evidence does not exist and a first-line option has not been tried, the right answer is the boring one.
These are clinical teaching cases. Patient identifiers, dates, and irrelevant details have been changed; the clinical reasoning is preserved. Not formal CME credit; a CME-accredited version is in development with our medical advisory board.