GLP-1 Agonists (Ozempic/Wegovy): Functional Medicine Support During Use

The Tool and the Terrain

Semaglutide — marketed as Ozempic for diabetes, Wegovy for weight loss, and tirzepatide (Mounjaro/Zepbound) combining GLP-1 and GIP activity — has become the most consequential pharmaceutical development in obesity treatment in decades. The weight loss is real: 15-20% of body weight in clinical trials. The appetite suppression is profound. For many patients who have failed every diet, every program, every attempt at willpower-based restriction, these medications offer the first experience of not being controlled by hunger.

Functional medicine does not dismiss this. Nor does it worship it.

The question is not whether GLP-1 agonists work. They do. The question is what happens alongside them, what happens without them, and what happens after them. Because a medication that suppresses appetite without addressing why appetite was dysregulated creates a dependency. And a medication that causes rapid weight loss without protecting the body’s composition, nutrient stores, and metabolic function creates a different kind of damage.

How GLP-1 Agonists Work

GLP-1 (glucagon-like peptide-1) is an incretin hormone released by L-cells in the small intestine after eating. It does four things: stimulates insulin secretion (glucose-dependent, so low hypoglycemia risk), suppresses glucagon, slows gastric emptying (food sits in the stomach longer), and signals satiety to the hypothalamus through vagal afferents and direct central action. The native hormone has a half-life of 2 minutes — DPP-4 enzymes degrade it almost immediately. Semaglutide is engineered to resist DPP-4 degradation, extending the half-life to approximately seven days, hence the weekly injection.

Tirzepatide adds GIP (glucose-dependent insulinotropic polypeptide) receptor agonism, which appears to enhance the weight loss effect beyond GLP-1 alone — SURMOUNT-1 trial showed 22.5% body weight loss at the highest dose.

The appetite suppression is not subtle. Patients describe food noise — the constant background hum of thinking about food — going silent for the first time in their lives. This is likely mediated through the brain’s reward circuitry: GLP-1 receptors are present in the nucleus accumbens, ventral tegmental area, and hypothalamus. Some patients also report reduced cravings for alcohol, nicotine, and compulsive behaviors — suggesting the mechanism extends beyond appetite into broader reward modulation.

The Muscle Mass Problem

This is the single most important concern and the least discussed. When weight is lost through caloric restriction alone — whether pharmaceutical or behavioral — approximately 25-40% of weight lost is lean mass (muscle, bone, organ tissue). The STEP-1 trial for semaglutide showed roughly 40% of weight lost was fat-free mass. This is catastrophic.

Muscle is the body’s metabolic engine. Every pound of muscle burns approximately 6 calories per hour at rest. Lose 15 pounds of muscle and resting metabolic rate drops by approximately 2,160 calories per day. This is why weight regain after stopping GLP-1 agonists is nearly universal — the body now burns significantly fewer calories than before treatment, but appetite hormones return to their original settings (or higher, as leptin plummets from reduced fat mass).

The solution is resistance training. This is not optional. It is as important as the medication itself. Patients on GLP-1 agonists who perform progressive resistance training 3-4 times per week preserve significantly more lean mass. The minimum effective dose: 2-3 sets of 8-12 repetitions per major muscle group, 2-3 times weekly, with progressive overload. A qualified trainer who understands the unique context of rapid weight loss is ideal.

Protein Requirements

The standard recommendation of 0.8g protein per kilogram of body weight is inadequate for anyone on GLP-1 agonists. The combination of caloric deficit and appetite suppression makes hitting protein targets actively difficult — patients simply do not feel like eating.

Minimum targets during GLP-1 use:

• Sedentary: 1.2g per kg of ideal body weight daily
• With resistance training: 1.4-1.6g per kg of ideal body weight daily
• Over 60: 1.6g per kg minimum (sarcopenia risk compounds age-related muscle loss)

For a person with an ideal body weight of 70 kg, this means 84-112g of protein daily. With suppressed appetite and slowed gastric emptying, this requires strategic effort:

• Protein-first eating: begin every meal with the protein component
• Protein supplementation: whey isolate, collagen peptides, pea protein, bone broth protein — 20-30g supplemental daily
• Spread intake across 3-4 meals (the body can only utilize approximately 30-40g per meal for muscle protein synthesis)
• Liquid protein (smoothies, bone broth) may be better tolerated than solid protein given delayed gastric emptying

Managing GI Side Effects

Nausea, constipation, and occasional vomiting are the most common side effects and the primary reason patients discontinue.

Nausea (40-50% of patients)

• Ginger: 250mg capsules 2-4 times daily, or ginger tea, or ginger chews. Evidence-based antiemetic (Viljoen 2014)
• Small, frequent meals rather than large ones (stomach is emptying slowly — do not overload it)
• Avoid lying flat for 30 minutes after eating
• Avoid high-fat meals initially (fat further delays gastric emptying)
• Peppermint tea or enteric-coated peppermint oil 200mg
• Dose titration: slow and gradual — stay at each dose level for 4+ weeks before increasing
• B6 25-50mg twice daily (anti-nausea, same mechanism used in pregnancy nausea)

Constipation (25-30% of patients)

Slowed gastric motility extends throughout the GI tract. Manage with:

• Magnesium citrate or oxide 400-800mg at bedtime (osmotic laxative effect)
• Ground flaxseed 2 tablespoons daily in smoothie
• Adequate water: 2.5-3 liters daily minimum
• Fiber increase (gradual — too fast worsens symptoms): vegetables, psyllium husk
• Movement: walking 20-30 minutes daily stimulates peristalsis
• Probiotic with motility support: Bifidobacterium lactis HN019 (Waller 2011 — reduced transit time)
• If severe: consider 2mg triphala at bedtime, or cascara sagrada short-term

Gastroparesis Risk

Cases of severe gastroparesis — stomach paralysis — have been reported, some persisting after medication discontinuation. Monitor for: persistent vomiting, severe abdominal pain, early satiety to the point of inability to eat, undigested food in vomit. This requires medical evaluation and possible gastric emptying study.

Nutrient Depletion During Rapid Weight Loss

Eating significantly less food means ingesting significantly fewer micronutrients. Combined with increased metabolic demands of tissue remodeling, this creates depletion risk:

Nutrient	Risk Factor	Dose
B-complex (methylated)	Reduced intake + increased demand	Complete B-complex daily
Zinc	Critical for immune, skin, taste	30mg daily with food
Magnesium	Already deficient in 50%+ of population	400mg glycinate or citrate
Omega-3 (EPA/DHA)	Anti-inflammatory, brain, mood	2g combined EPA/DHA
Vitamin D3	Fat-soluble, may be released from fat stores erratically	Test and target 50-80 ng/mL
Iron	Monitor ferritin, especially menstruating women	Only supplement if deficient
Probiotics	GI microbiome disruption from motility changes	Multi-strain, 20-50 billion CFU
Collagen peptides	Support connective tissue during rapid remodeling	10-15g daily

The Gallbladder Problem

Rapid weight loss is the single strongest modifiable risk factor for gallstone formation. Fat stored in adipose tissue releases cholesterol when mobilized. This cholesterol is excreted through bile. When the gallbladder receives a sudden surge of cholesterol-saturated bile without adequate stimulation (because the person is eating less fat), stones form. The STEP trials reported gallbladder-related events in 1.5-2.5% of participants — likely an undercount given short follow-up.

Prevention strategy:

• Do not go ultra-low-fat — include moderate healthy fat at each meal to stimulate gallbladder contraction
• Ursodeoxycholic acid (UDCA) 300mg twice daily — the standard prophylaxis for gallstone formation during rapid weight loss (Sugerman 1995, Shiffman 1995). Discuss with prescribing physician
• Bile support supplements: taurine 500-1000mg (conjugates bile acids), ox bile 125-500mg with fatty meals, phosphatidylcholine 1200mg, artichoke extract 500mg (choleretic)
• Beet consumption or beet-derived betaine: supports bile flow
• Warning signs: right upper quadrant pain after fatty meals, pain radiating to right shoulder blade, nausea after eating — get ultrasound evaluation

What Happens After Stopping

The STEP-4 trial data is sobering. Participants who discontinued semaglutide after 20 weeks regained two-thirds of the weight lost within one year. Appetite hormones — ghrelin, leptin, GLP-1, PYY — returned to pre-treatment levels. The “food noise” returned. For many patients, stopping felt like the end of the only thing that had ever worked.

This is where functional medicine offers its deepest value — not as a replacement for the medication, but as the work that gives the medication an exit strategy.

The Parallel Protocol: Building the Off-Ramp

While using the GLP-1 agonist, simultaneously address every root cause driving appetite dysregulation and metabolic dysfunction:

Fix Insulin Resistance

The medication suppresses appetite, but if the underlying insulin resistance is not resolved, metabolic dysfunction persists. Berberine 500mg twice daily, chromium 200-1000mcg, alpha-lipoic acid 600mg, magnesium, resistance training, time-restricted eating (when tolerated alongside the medication).

Optimize Thyroid

Hypothyroidism — even subclinical — slows metabolic rate and promotes weight regain. Test full thyroid panel (TSH, free T4, free T3, reverse T3, TPO antibodies, thyroglobulin antibodies). Address Hashimoto’s if present. Optimize T3 levels.

Address Emotional Eating

If the medication has silenced food noise but the underlying trauma, stress patterns, and nervous system dysregulation have not been addressed, stopping the medication will reactivate the same patterns. This window of reduced cravings is the optimal time for therapy — somatic experiencing, IFS, EMDR, mindful eating training.

Heal the Gut

Optimize the microbiome (Akkermansia muciniphila is associated with better metabolic outcomes — Depommier 2019). Address SIBO, dysbiosis, intestinal permeability. Support GLP-1’s natural production by gut microbes through prebiotic fiber (when tolerated).

Reduce Systemic Inflammation

Inflammation drives leptin resistance. Anti-inflammatory diet, omega-3, curcumin 1000mg, adequate sleep, stress management.

Long-Term Monitoring

Every patient on a GLP-1 agonist should have regular monitoring beyond standard labs:

• DEXA scan: Body composition at baseline, 6 months, and 12 months. Tracking lean mass preservation is critical — scale weight alone is misleading
• Metabolic panel: Comprehensive metabolic panel, lipids, HbA1c, fasting insulin, HOMA-IR
• Nutrient levels: B12, folate, vitamin D, zinc, magnesium, ferritin, complete iron panel
• Thyroid panel: TSH, free T4, free T3 (rapid weight loss can affect thyroid hormone conversion)
• Gallbladder ultrasound: At baseline and 6 months if not already done, especially with symptoms
• Bone density: Consider DEXA bone density in postmenopausal women and anyone losing >15% body weight

The Honest Conversation

GLP-1 agonists are powerful tools. For some patients — particularly those with severe obesity, type 2 diabetes, or cardiovascular risk — they may be life-saving. Functional medicine is not anti-medication. It is anti-monotherapy. It objects to a model where the medication is the entire treatment plan, where the patient receives a weekly injection and no other intervention, and where the inevitable discontinuation leads to predictable regain because nothing underneath has changed.

The best outcome: use the medication to create a window of reduced appetite, use that window to do the deep work — fix the metabolism, heal the gut, address the trauma, build the muscle, rewire the habits — and then taper the medication with a functional foundation in place.

Is the medication treating the disease, or is it buying you time to treat the terrain?