The Incretin Effect in One Paragraph

GLP-1 (glucagon-like peptide-1) is a gut hormone released after meals. It does four things that matter clinically: potentiates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and acts centrally to reduce appetite. GLP-1 receptor agonists are long-acting analogs that exploit all four effects. Tirzepatide adds a GIP receptor agonist component, which amplifies the weight-loss signal. The slowed gastric emptying is what drives both the GI side-effect burden and the peri-op aspiration concern.

Who Gets These Drugs — and Why

Your patients are on these drugs because they work — the weight, glucose, CV, and renal signals are real. The PT's job is not to second-guess the prescription; it is to manage the tradeoffs while the patient benefits.

Renal and Cardiovascular Signals — What to Expect, Not What to Fear

• Mild eGFR dip on initiation is expected and not harmful — similar to SGLT2i and RAAS blockers.
• Improved long-term kidney outcomes (FLOW).
• Reduced major adverse CV events across LEADER, SELECT, and other CV outcomes trials.
• Heart-failure benefit in HFpEF + obesity specifically (STEP-HFpEF) — symptomatic and functional.

None of these benefits require anything specific from PT — they accrue as long as the patient stays on therapy and avoids the pitfalls below.

The Sarcopenia Signal — the Most PT-Relevant Concern

Weight loss on GLP-1 RAs is not proportional across compartments. Body-composition sub-studies of semaglutide and tirzepatide show that approximately 25–40% of total weight loss comes from lean mass rather than fat, depending on the drug, dose, and whether the patient resistance-trains. This is similar to lean-mass loss in any calorie-deficit weight-loss program, but the speed of GLP-1–driven weight loss amplifies it. For older adults, sarcopenic-obesity patients, and anyone with pre-existing functional limitations, this matters a lot — lost lean mass predicts falls, sarcopenia, and loss of independence.

Resistance training protects lean mass during GLP-1 therapy. The exact quantitative benefit varies by study, but the direction of effect is consistent: patients who resistance-train during weight loss preserve more lean mass and come out of the weight-loss course stronger, not weaker. PT is the intervention.

GI Side Effects — the #1 Reason Patients Stop

• Nausea, vomiting, diarrhea, constipation, abdominal discomfort — worst during titration, usually diminishes over 4–8 weeks.
• Severe enough in some patients to impair food intake (protein intake in particular) and reduce exercise tolerance.
• Rare: pancreatitis (stop drug, seek care); gastroparesis worsening in diabetic patients.

The SELECT trial had 16.6% discontinuation for adverse events in the semaglutide arm vs 8.2% placebo^[2] — so roughly 1 in 6 patients will stop because of GI burden. Expect this.

The High-Risk Patient Profile

• Older adults — sarcopenia risk amplified; falls; frailty.
• Patients on insulin or sulfonylureas — hypoglycemia risk when combined with GLP-1 RA, especially with missed meals.
• Patients in the first 4–8 weeks of titration — GI symptoms, volume shifts, early orthostatic changes.
• Patients heading to surgery within the next 1–2 weeks — aspiration risk.
• Patients with a history of diabetic gastroparesis — may be exacerbated.
• Patients with rapid weight loss (>1 kg/week sustained) — higher lean-mass loss, more orthostasis.

Red Flags — What to Watch For During PT

Decision Algorithm

Patient on a GLP-1 RA (or GIP/GLP-1) arrives to PT
        ↓
Surgery in the next 1–2 weeks?
        ├── YES → Verify surgical team knows the hold plan per current
        │         ASA/ADA guidance. Do NOT tell patient to hold the
        │         drug on your own — coordinate with prescriber.
        │
        └── NO  → Continue below.
        ↓
In the first 4–8 weeks of titration?
        ├── YES → Expect GI symptoms, orthostasis. Modify intensity;
        │         shorter sessions; check orthostatic vitals.
        │
        └── NO  → Likely at steady state; proceed with normal progression.
        ↓
Is the patient losing weight rapidly (>1 kg/week) or already 10%+ down?
        ├── YES → Resistance training is the priority. Add protein
        │         counseling. Screen for sarcopenia markers.
        │
        └── NO  → Proceed with normal PT plan; still emphasize resistance
                  training as part of the program.
        ↓
Red flag present?
        ├── YES → Pause session. Escalate to prescribing clinician or
        │         urgent care/ED per severity.
        │
        └── NO  → Proceed, reinforce teaching, document.

4b. Resistance Training Prescription (the Non-Negotiable)

• Frequency: 2–3 sessions/week, non-consecutive days.
• Volume: cover all major muscle groups — legs, hips, back, chest, shoulders, arms, core. Include compound lifts when possible.
• Intensity: moderate-to-high — 60–80% 1RM or RPE 6–8 on a 10-point scale. Light-weight "toning" does not protect lean mass adequately.
• Sets/reps: 2–3 sets of 8–12 reps per exercise is a reasonable starting point; progress load as tolerated.
• Supervision: higher in early weeks when orthostasis + GI fatigue are worst.
• Aerobic training: add it, but do not substitute for resistance training. Aerobic alone does not adequately protect lean mass during rapid weight loss.

4c. Peri-Operative Holds — the Aspiration Story

Delayed gastric emptying from GLP-1 RAs has led to case reports of pulmonary aspiration during anesthesia despite appropriate NPO windows. This drove a 2023 American Society of Anesthesiologists (ASA) consensus-based guidance recommending that GLP-1 RAs be held before elective procedures requiring general or deep sedation^[5]. Current practice is evolving; a 2023 ADA/multi-society statement urges balance between hold risk and glycemic control. General pattern:

• Daily formulations (liraglutide): hold the day of the procedure.
• Weekly formulations (semaglutide, dulaglutide, tirzepatide): hold the week before the procedure.
• Rapid-sequence or full-stomach precautions if surgery proceeds without holding.

PT's role: in pre-habilitation or pre-op PT visits, ask about the hold plan and confirm the surgical team has addressed it. Do NOT tell the patient to hold the medication on your own authority — that is a prescribing decision. Escalate if the patient seems unaware of the plan.

4d. Protein Counseling (quick version — full module later in this series)

• Target 1.2–1.6 g/kg/day in most adults during GLP-1 therapy — higher than the sedentary baseline (0.8 g/kg/day) to offset calorie deficit.
• Distribute across 3–4 meals (target approximately 25–40 g protein per meal — leucine threshold).
• If GI side effects are limiting food intake, protein-first eating (eat the protein portion of the meal first) helps.
• Coordinate with a dietitian or prescribing clinician; do not improvise a CKD patient's protein dose — the rules change in kidney disease (covered in the Protein PT handout later in this series).

4e. Hypoglycemia — When GLP-1 Is Combined With Insulin or Sulfonylurea

• GLP-1 RAs alone rarely cause hypoglycemia — insulin secretion is glucose-dependent.
• Combined with insulin or sulfonylurea, hypoglycemia risk rises substantially, especially if food intake drops due to GI symptoms.
• PT action: if the patient reports tremor, sweating, lightheadedness, confusion — check glucose if able. Treat with 15 g fast carbohydrate, recheck in 15 minutes. Notify prescribing clinician.

Scripts You Can Use Today

When to Call — Give the Patient the List

1. Severe, persistent abdominal pain — especially to back.
2. Vomiting for more than a day, or inability to keep fluids down.
3. New lightheadedness standing up, or falls.
4. Weight loss faster than about 2 lb per week, for more than two weeks.
5. Low blood sugar symptoms (if on insulin or sulfonylurea).
6. Surgery scheduled and no plan to hold the medication has been discussed.
7. Signs of dehydration — dry mouth, reduced urine, dark urine, weakness.