GLP-1 Stack Guide 2026: NAD+, B12, Sermorelin & Adjunct Protocols
Updated May 6, 2026 · By Chad Simpson
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What Is GLP-1 Stacking?
GLP-1 stacking refers to combining a GLP-1 receptor agonist — semaglutide (Wegovy, Ozempic, or compounded) or tirzepatide (Mounjaro, Zepbound) — with one or more adjunct therapies to address side effects, support lean muscle preservation, improve energy, or optimize overall metabolic outcomes during weight loss.
The concept comes from the longevity medicine and functional medicine communities and has moved into mainstream telehealth weight loss programs. Providers like Eden Health and Ivim Health now market bundled GLP-1 + adjunct protocols rather than GLP-1 monotherapy alone.
Important Caveat Upfront
None of the stacks described here have RCT data confirming additive weight loss benefit over GLP-1 monotherapy. The rationale for most is mechanistic (biologically plausible) or based on independent evidence for the adjunct compound alone. All stacks require physician supervision. Do not self-prescribe adjunct peptides or inject anything not prescribed by a licensed physician.
Why Stack? The Lean Mass Problem
GLP-1 agonists produce weight loss primarily by reducing appetite and caloric intake. This caloric deficit is effective — but it is not selective. The STEP-1 semaglutide trial showed that approximately 25% of total weight lost was lean mass (muscle and bone density). This is similar to other caloric restriction approaches and is a known limitation of all non-exercise-based weight loss interventions.
Strategies to mitigate lean mass loss during GLP-1 therapy include resistance training (best evidence), adequate protein intake (1.2–1.6g/kg body weight), and adjunct therapies like sermorelin or NAD+. Tirzepatide (dual GIP/GLP-1) may have a more favorable lean mass preservation profile than semaglutide alone — SURMOUNT trials showed better lean mass retention — but data is still emerging.
5 Common GLP-1 Stacks
GLP-1 + NAD+ (Injection or IV)
Most Popular AdjunctRationale
During caloric restriction, the cell switches to a fasting-like metabolic state that upregulates sirtuins — a family of NAD+-dependent deacetylase enzymes involved in mitochondrial biogenesis, fat oxidation, and cellular stress response. The hypothesis: supplemental NAD+ (via injection or IV infusion) may support sirtuin function during the significant caloric deficit induced by GLP-1s, potentially preserving lean mass and cellular energy during weight loss.
Evidence Base
No published RCT directly tests NAD+ as a GLP-1 adjunct. Mechanistic rationale is biologically plausible. NAD+ IV therapy has been studied independently for metabolic and fatigue indications.
Available From
- Eden Health (GLP-1 + NAD+ programs)
- Ivim Health (liraglutide + NAD+ protocols)
GLP-1 + Sermorelin (Growth Hormone Peptide)
Lean Mass FocusRationale
Sermorelin is a synthetic analogue of growth hormone-releasing hormone (GHRH). It stimulates the pituitary to release endogenous growth hormone. During a GLP-1-induced caloric deficit, growth hormone levels naturally decline. Sermorelin co-administration aims to maintain or restore GH signaling to support muscle protein synthesis and reduce lean mass losses — a key concern given that ~25% of weight lost in STEP-1 was lean tissue.
Evidence Base
Sermorelin is well-studied for GH deficiency but has no published RCT data as a GLP-1 combination therapy for lean mass preservation. Off-label use in longevity and anti-aging medicine is common.
Available From
- Physician-supervised compounding programs (provider varies)
GLP-1 + Vitamin B12
Fatigue SupportRationale
Fatigue and low energy are among the most common early side effects of GLP-1 agonists, particularly during dose titration. Vitamin B12 (methylcobalamin or cyanocobalamin) is included in some compounded semaglutide formulations under the rationale that B12 supports neurological function, energy metabolism via the methylation cycle, and red blood cell production. B12 deficiency itself causes fatigue — and patients on caloric restriction may have dietary B12 shortfalls.
Evidence Base
No controlled trial data isolates B12's contribution in combination semaglutide + B12 formulations. B12 inclusion is low-risk and low-cost. Some providers market this as a meaningful differentiator; evidence doesn't support strong claims of additive weight loss benefit.
Available From
- TMates (confirmed semaglutide + B12 formulation)
- Various 503A compounders
GLP-1 + Lipotropic Injections (MIC/B12)
Liver & Fat MetabolismRationale
Lipotropic injections typically combine methionine, inositol, and choline (MIC) with B12. The methionine-inositol-choline triad theoretically supports hepatic fat export and fatty acid metabolism — relevant during rapid weight loss when the liver processes a high load of mobilized fat. Some providers include lipotropic injections as an adjunct to GLP-1 programs to support liver function and accelerate fat mobilization.
Evidence Base
Lipotropic injection efficacy for weight loss is not supported by large RCTs. Individual components (choline, inositol) have metabolic roles but the injectable combination has limited controlled trial data. Used as a supportive adjunct, not a primary intervention.
Available From
- Various medical weight loss clinics
- Some telehealth programs
GLP-1 + Metformin
Best Evidence BaseRationale
Metformin is a first-line type 2 diabetes drug with decades of safety data and established metabolic effects: AMPK activation, hepatic glucose production suppression, and mild insulin sensitization. It is already co-prescribed with GLP-1 agonists in T2D guidelines. For obesity patients without diabetes, metformin is used off-label based on AMPK pathway overlap with GLP-1 mechanisms, potential gut microbiome modulation, and possible attenuation of muscle loss via AMPK activation.
Evidence Base
Well-studied in T2D where combination with GLP-1 agonists is standard of care. RCT data for metformin as an obesity stack adjunct (non-diabetic patients) is limited but mechanistically credible. Longest-studied agent on this list.
Available From
- Most telehealth providers can prescribe metformin off-label
Providers Offering GLP-1 + Adjunct Programs
Most standard telehealth GLP-1 programs are monotherapy. The following providers specifically offer bundled GLP-1 + adjunct protocols as of May 2026:
Eden Health
Broadest Adjunct ProgramOffers GLP-1 programs that can be bundled with NAD+ injection therapy. Physician intake included. NAD+ can be added to semaglutide or tirzepatide programs. Comprehensive telehealth platform with ongoing provider access.
Adjuncts: NAD+ injections, optional peptide protocols
See Eden Health ProgramsIvim Health
Microdosing-focused GLP-1 protocols (liraglutide-based) combined with NAD+ therapy. Ivim positions itself as a longevity-forward provider and explicitly bundles NAD+ infusion or injection support alongside weight loss programs.
Adjuncts: NAD+ infusions/injections, liraglutide microdosing protocols
See Ivim Health ProgramsTMates
Verified on brand site Invalid DateConfirmed semaglutide + B12 compounded formulation. If B12 inclusion matters to you (fatigue support during titration), TMates offers this as standard in their compounded semaglutide program.
Adjuncts: B12 included in compounded semaglutide formulation
See TMates PlansWhat the Evidence Does and Doesn't Support
| Stack | Biologically Plausible | RCT as GLP-1 Adjunct | Risk Level |
|---|---|---|---|
| GLP-1 + NAD+ | Yes | No | Low–Moderate (cost) |
| GLP-1 + Sermorelin | Yes | No | Moderate (GH axis effects) |
| GLP-1 + B12 | Modest | No | Very Low |
| GLP-1 + Lipotropics | Theoretical | No | Low |
| GLP-1 + Metformin | Yes (T2D standard of care) | Yes (for T2D); limited for obesity | Low (if renally cleared) |
The absence of RCT data doesn't mean these combinations are ineffective — it means they haven't been studied as GLP-1 combinations. The metformin + GLP-1 combination has the strongest evidence base because it is standard of care in type 2 diabetes. For the others, you are accepting biologically plausible reasoning alongside the GLP-1's proven efficacy. A conservative physician will recommend GLP-1 + resistance training + adequate protein before adding any other adjunct.
Frequently Asked Questions
What does "GLP-1 stacking" mean?
Combining a GLP-1 receptor agonist (semaglutide or tirzepatide) with adjunct therapies — NAD+, B12, sermorelin, lipotropics, or metformin — to address side effects, preserve lean muscle, or support metabolic outcomes. All stacks require physician supervision.
Do GLP-1 medications cause muscle loss?
GLP-1s cause a caloric deficit that is not muscle-selective. In STEP-1, approximately 25% of total weight lost was lean mass. This is comparable to other caloric restriction approaches. Resistance training and adequate protein remain the best-evidence strategies for lean mass preservation.
Does NAD+ help with GLP-1 side effects?
No RCT specifically tests this. The rationale is mechanistic: caloric restriction activates NAD+-dependent sirtuins. Whether supplemental NAD+ meaningfully improves GLP-1 outcomes is not established by clinical evidence.
Is sermorelin safe to take with semaglutide?
No published safety studies cover the combination. It is used off-label in physician-supervised settings. Sermorelin affects the GH/IGF-1 axis and requires physician evaluation including baseline lab work before prescribing.
What providers offer GLP-1 + NAD+ bundled programs?
Eden Health and Ivim Health both offer GLP-1 programs that can be bundled with NAD+ therapy. Expect $300–$700/month for bundled programs depending on the specific protocol.
Does semaglutide with B12 reduce side effects?
B12 is included in some compounded semaglutide formulations to support energy metabolism and reduce fatigue during titration. No controlled trial data isolates B12's contribution. TMates and other providers offer B12-inclusive formulations.
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