Peptides for Medical Professionals

Core topics

What's covered

Click any topic to expand a deeper drill-down with mechanism, key references, and a take-home summary.

Learning objectives

By the end of this module you will be able to

L01Place semaglutide, liraglutide, and dulaglutide on a dosing/efficacy comparison.
L02State the SELECT trial result and what it changed about prescribing.
L03Counsel a patient about MTC/MEN2 contraindication, gallbladder risk, and gastroparesis warnings.
L04Identify three real risks of compounded semaglutide.

Expected takeaways

What you should walk away believing

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Takeaway mastery

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Lesson · Core emphasis

What this means for you

Patient summary

GLP-1 medications mimic a natural gut hormone that tells your brain you're full and your pancreas to release insulin only when blood sugar is high. They cause meaningful weight loss, lower diabetes complications, and reduce heart attacks. Side effects are mostly GI (nausea, constipation) and improve over weeks.

Clinician summary

Dose escalation is the difference between a tolerable course and a discontinuation. Start low, escalate on the manufacturer schedule, and counsel for nausea/early satiety. Monitor for gallstones (especially with rapid weight loss) and sarcopenia in older or frailer patients (consider DXA / resistance training pairing).

Advanced note

The GIP arm of tirzepatide adds efficacy without proportional GI burden — receptor pharmacology is non-additive. Watch retatrutide (GLP-1/GIP/glucagon) and oral orforglipron.

Diagram

Visual reference

Myth-buster

Patients who stop GLP-1s regain all the weight, so the drugs don't 'work'.

Reality

STEP-4 showed substantial regain after discontinuation — but this is also true for antihypertensives. Obesity is a chronic disease; chronic treatment is the default expectation, not a failure mode.

Case study

Recurrent nausea limiting titration

62-year-old woman with T2D (HbA1c 8.4%), BMI 34, on metformin. Started semaglutide 0.25 mg → 0.5 mg → 1.0 mg, but at 1.0 mg has persistent nausea, early satiety, and one episode of vomiting per week. She wants to continue therapy.

Question

What is your next step before considering discontinuation?

Evidence-graded claims

What the data say

A

Semaglutide reduces 3-point MACE by ~20% in patients with established CVD without diabetes (SELECT)

Lincoff et al., NEJM 2023.

A

Semaglutide reduces composite kidney/CV outcome in T2D + CKD (FLOW)

Perkovic et al., NEJM 2024. Trial stopped early for benefit.

C

GLP-1 RAs slow Parkinson's disease progression

Lixisenatide LIXIPARK (NEJM 2024) modest signal; exenatide PD-2 negative. Pre-specified meta still hypothesis-generating.

D

Semaglutide causes thyroid C-cell tumors in humans

Rodent finding; human signal uncertain. Class label remains, MTC/MEN2 remain contraindications.

F

Compounded GLP-1s save patients money safely during shortages

FDA adverse-event reports include dosing errors, overdoses, and infections; salt forms are not interchangeable.

Case vignettes

Apply it

The thyroid nodule incidentally found

55-year-old man with T2D and BMI 36 wants semaglutide. On exam you palpate a 1.5 cm right thyroid nodule. Family history is unremarkable.

Most appropriate next step before prescribing?

A.Prescribe semaglutide; the MTC signal is rodent-only
Order thyroid ultrasound and TFTs; defer GLP-1 RA pending workup
C.Refer to endocrine surgery first
D.Prescribe a non-GLP-1 weight-loss drug instead without imaging

Rationale ·A palpable nodule warrants ultrasound regardless of GLP-1 plans. Once benign etiology is established, GLP-1 RA can be considered if no MTC/MEN2 history.

Quick check

Test yourself

Q1Which is an ABSOLUTE contraindication to GLP-1 RA therapy?

Q2What did SELECT (2023) demonstrate?

Q3Most common reason for early GLP-1 discontinuation?

Flashcards · Spaced repetition

Lock it in — review what's due

Due5Total5

FrontNew

5 in queue

Semaglutide MOA?

Click to reveal answer

Glossary

Key terms & abbreviations

Incretin effect: Greater insulin response to oral than IV glucose at matched glycemia, mediated by GLP-1 and GIP.
MASHMetabolic dysfunction-associated steatohepatitis: Formerly NASH. GLP-1 and dual/triple agonists show histologic improvement in trials.
MEN2Multiple Endocrine Neoplasia type 2: RET mutation syndrome predisposing to MTC; absolute contraindication to GLP-1 RAs.

Optional deeper dive

Semaglutide and Cardiovascular Outcomes (SELECT) — Lincoff AM et al., NEJM 2023
Effects of Semaglutide on Chronic Kidney Disease in T2D (FLOW) — Perkovic V et al., NEJM 2024
Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP-1) — Wilding JPH et al., NEJM 2021

References · 8

Sources cited in this module

[1]
Standards of Care in Diabetes — 2025
American Diabetes Association · 2025Guideline · T1
[2]
Medications containing semaglutide marketed for type 2 diabetes or weight loss
U.S. FDA Drug Safety Communication · 2024Regulatory · T1
[3]
Effects of Semaglutide on Chronic Kidney Disease in Patients with T2D (FLOW)
Perkovic V. et al. · NEJM · 2024RCT · T1
[4]
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Lincoff AM. et al. (SELECT) · New England Journal of Medicine · 2023RCT · T1
[5]
Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)
Wilding JPH. et al. · NEJM · 2021RCT · T1
[6]
Daily Oral Orforglipron in Adults with Type 2 Diabetes — Phase 2
Frias JP. et al. · NEJM · 2023RCT · T2
[7]
The discovery and development of liraglutide and semaglutide
Knudsen LB, Lau J. · Frontiers in Endocrinology · 2019Review · T2
[8]
Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide
Lau J. et al. · Journal of Medicinal Chemistry · 2015Mechanism / preclinical · T2

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GLP-1 Receptor Agonists