# Cannabis Use With GLP-1 Therapy: What a Diabetes Cohort Found

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/cannabis-glp1-diabetes-cardiovascular-kidney-risk/
> **Published:** 2026-08-03T23:25:14-04:00 | **Last Modified / Clinically Audited:** 2026-09-27T22:01:26-04:00
> **Clinical Summary:** Cannabis and GLP-1 therapy were linked to higher heart, kidney, and mortality risks in a matched diabetes cohort, but causality remains unproven.

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CED Clinical Relevance #84 Safety Signal A newly indexed, peer-reviewed matched cohort addresses a current clinical question in 8,234 adults with type 2 diabetes receiving GLP-1 receptor agonists. The associations are clinically important, but retrospective diagnosis-code exposure and residual confounding prevent causal interpretation.

Clinical Insight | CED Clinic
A retrospective health-record study found that adults with type 2 diabetes who had repeated cannabis-related diagnosis codes before starting a GLP-1 receptor agonist experienced higher rates of death, major cardiovascular events, and major kidney events than matched patients without those codes. The findings persisted after matching on more than 40 measured characteristics and in sensitivity analyses. They are a meaningful safety signal, not evidence that cannabis caused the outcomes or erased the established benefits of GLP-1 therapy. Diagnosis codes may identify a population with [cannabis use disorder](https://cedclinic.com/sex-differences-cannabis-stress-reactivity-oxytocin/), heavier exposure, other substance use, barriers to care, or unmeasured illness that the database could not fully capture. The practical response is better history-taking and risk assessment, not abrupt medication changes based on an observational association.

[Cannabis Safety](https://cedclinic.com/respiratory-effects-inhalational-marijuana/)Type 2 DiabetesGLP-1 TherapyCardiovascular RiskKidney Risk

Audience
Adults with type 2 diabetes, clinicians prescribing GLP-1 receptor agonists, caregivers, and cannabis-science readers

Primary Topic
[cannabis use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/) among adults with type 2 diabetes starting GLP-1 receptor agonist therapy

Source
[Read the full source](https://pubmed.ncbi.nlm.nih.gov/42546368/)

A retrospective matched cohort compared 4,117 cannabis-coded adults with 4,117 controls after GLP-1 therapy initiation. Cannabis coding was associated with higher mortality, cardiovascular events, and kidney events over a median 2.6 years, but the design cannot establish that cannabis caused those outcomes.

What This Study Teaches Us
Repeated cannabis-related diagnosis codes identified a GLP-1-treated diabetes group with higher observed risks after extensive measured matching. The result supports clinical screening and prospective research, while leaving exposure detail, causality, and residual confounding unresolved.

Why This Matters
GLP-1 receptor agonists are widely used for type 2 diabetes and carry established cardiovascular and kidney benefits in appropriate patients. Many patients also use cannabis. Clinicians need evidence-literate ways to discuss that overlap without assuming safety or overstating a database association.

Study Snapshot

Study Type
Retrospective propensity score-matched cohort study

Data Source
TriNetX Research Network, January 2017 through December 2025

Eligible Population
614,333 adults with type 2 diabetes initiating GLP-1 receptor agonist therapy

Matched Cohorts
4,117 people with cannabis-related codes and 4,117 comparison patients

Cannabis Definition
At least two ICD-10-CM F12.x codes in the two years before GLP-1 therapy initiation

Matching
More than 40 measured baseline covariates

Median Follow-up
2.6 years

Primary Outcome
All-cause mortality

Secondary Outcomes
Four-point major adverse cardiovascular events and major adverse kidney events

Mortality Association
Hazard ratio 1.64; 95% CI 1.38 to 1.96

Cardiovascular Association
Hazard ratio 1.42; 95% CI 1.26 to 1.59

Kidney Association
Hazard ratio 1.55; 95% CI 1.34 to 1.79

Exposure Gradient
Mortality HR 2.20 for [cannabis use disorder](https://cedclinic.com/sex-differences-cannabis-stress-reactivity-oxytocin/) and 1.73 for non-disordered use categories

Robustness Check
Reported E-values ranged from 2.21 to 2.63

Major Limitation
Observational coded-record design with no product, dose, route, timing, adherence, or complete behavioral detail

Journal
Drug and Alcohol Dependence

Published Online
July 29, 2026

Authors
Aseel Salameh and colleagues

PMID / DOI
42546368 / 10.1016/j.drugalcdep.2026.113296

Clinical Bottom Line
This large matched cohort raises a clinically important safety signal among cannabis-coded adults with diabetes starting GLP-1 therapy. It justifies careful screening and prospective study, but it does not prove that cannabis caused cardiovascular, kidney, or mortality outcomes.

What the Researchers Compared

Investigators identified adults with type 2 diabetes who initiated GLP-1 receptor agonist therapy in a multinational health-record network. People with at least two cannabis-related diagnosis codes in the prior two years were matched one-to-one with comparison patients.

Matching covered more than 40 recorded characteristics. That can improve comparability for measured factors, but it cannot recover exposures or vulnerabilities that were never recorded accurately.

What the Associations Showed

Over a median 2.6 years, the cannabis-coded cohort had higher observed all-cause mortality, major cardiovascular events, and major kidney events. Confidence intervals excluded no association for all three outcomes.

The authors also reported a stronger mortality association in the [cannabis use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/) disorder category than in the non-disordered cannabis category. That pattern strengthens the safety signal but does not, by itself, establish a biological dose-response.

Why Diagnosis Codes Are an Imperfect Exposure Measure

F12.x codes do not specify THC or CBD content, dose, route, frequency, current use, medical authorization, product quality, or whether use continued after GLP-1 initiation.

Repeated coding may preferentially identify people whose [cannabis use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/) was clinically visible, problematic, or connected to other health and social risks. It should not be treated as equivalent to every form of cannabis exposure.

Association Is Not Proof of Harm

Propensity matching balances recorded covariates, but unmeasured confounding can remain. Tobacco, alcohol, other substances, socioeconomic conditions, health-care access, medication adherence, diabetes severity, frailty, and reasons for cannabis use may be incompletely captured.

Reverse causation is also possible when people with greater symptom burden are more likely to use cannabis or acquire a diagnosis code. A hazard ratio describes an association in this dataset, not a guaranteed effect for an individual patient.

What Clinicians Can Do Now

Ask about the actual product, cannabinoid content, dose, route, frequency, reason for use, impairment, tobacco co-use, other substances, and symptoms of [cannabis use disorder](https://cedclinic.com/sex-differences-cannabis-stress-reactivity-oxytocin/). Review cardiovascular and kidney risk, glycemic management, and medication adherence in context.

The paper does not support stopping GLP-1 therapy or cannabis automatically. It supports a more complete conversation, risk-factor optimization, and monitoring while prospective studies clarify whether the association reflects exposure, patient selection, or both.

How Strong Is This Evidence?
The study used a large source population, matched 8,234 patients on more than 40 recorded factors, examined clinically important outcomes, reported confidence intervals, explored cannabis use disorder separately, and used sensitivity analyses and E-values to test robustness.

Where This Paper Deserves Skepticism
Retrospective database matching cannot remove unmeasured confounding. Cannabis exposure was inferred from diagnosis codes rather than verified product, dose, route, frequency, biomarkers, or continued use. Coding may select a clinically different population, and the exploratory SGLT-2 findings should not be interpreted as a protective prescribing rule.

What This Paper Does Not Show
The study does not prove that cannabis causes death, heart events, or kidney events; show that occasional use carries the reported risk; distinguish THC from CBD; establish a safe dose; show that cannabis cancels GLP-1 benefits; or justify stopping either therapy without individualized review.

How This Fits With the Broader Clinical Conversation

Randomized trials establish cardiovascular and kidney benefits for several GLP-1 receptor agonists in defined populations. This observational paper asks a different question: whether cannabis-coded patients receiving those drugs have different real-world outcomes.

The next step should be prospective work with validated exposure measurement, product and dose detail, tobacco and substance-use assessment, disease severity, adherence, and patient-centered reasons for cannabis use.

Dr. Caplan’s Take

*I would use this study as a prompt to ask better questions, not as a reason to frighten patients. A repeated cannabis diagnosis code carries more clinical information than a simple yes-or-no use history, but it still does not tell us what product was used, how much, or why.*

*For a patient with diabetes, the practical priorities remain cardiovascular and kidney risk reduction, medication adherence, glycemic care, and an honest review of cannabis exposure. The association deserves attention while causality remains unproven.*

What a Careful Reader Should Take Away
The signal is strong enough to improve screening and counseling, but not strong enough to assign causation or make automatic treatment changes.

Evidence Interpretation Guide

Table of Contents

- [How to Interpret the Cannabis and GLP-1 Safety Signal](#How_to_Interpret_the_Cannabis_and_GLP-1_Safety_Signal)[A Four-Step Reading Frame](#A_Four-Step_Reading_Frame)
- [The Same Study Can Mean Different Things Depending on the Question Being Asked](#The_Same_Study_Can_Mean_Different_Things_Depending_on_the_Question_Being_Asked)[Bring Specifics to the Conversation](#Bring_Specifics_to_the_Conversation)
- [Screen Beyond a Yes-or-No Question](#Screen_Beyond_a_Yes-or-No_Question)
- [Coding Can Select a Different Population](#Coding_Can_Select_a_Different_Population)
- [Residual Confounding Remains](#Residual_Confounding_Remains)
- [A New Question About a High-Risk Population](#A_New_Question_About_a_High-Risk_Population)
- [Optimize Established Risk Factors](#Optimize_Established_Risk_Factors)
- [Measure Cannabis Exposure Directly](#Measure_Cannabis_Exposure_Directly)
- [Clinical Data Need Product Clarity](#Clinical_Data_Need_Product_Clarity)
- [Frequently Asked Questions](#Frequently_Asked_Questions)[Related](#Related)

## How to Interpret the Cannabis and GLP-1 Safety Signal

Large observational studies can reveal clinically important patterns.

Four checks keep this pattern from becoming a causal claim.

### A Four-Step Reading Frame

**Identify the exposure**The study measured repeated cannabis-related diagnosis codes, not a standardized cannabis product or verified dose.

**Separate matching from randomization**Matching can balance recorded factors, but only randomization balances measured and unmeasured factors by design.

**Read relative risk with context**Hazard ratios describe group associations and do not provide an individual’s absolute risk without baseline-event data.

**Translate to action carefully**The immediate clinical response is better assessment and risk optimization, not an automatic medication change.

The Research Question
Were cannabis-related diagnosis codes associated with cardiovascular, kidney, and mortality outcomes among adults with diabetes starting GLP-1 therapy?

The Patient Question
Does this mean cannabis is unsafe for me if I take a GLP-1 medication?

The Bottom Line
The study raises a safety signal that warrants individualized review, while causality and product-specific risk remain unknown.

CED Perspective Lens

## The Same Study Can Mean Different Things Depending on the Question Being Asked

Scientific papers rarely answer a single question. Patients, clinicians, researchers, policymakers, and critics often read the same data differently. The perspectives below explore how this study looks through several evidence-based lenses.

Lens Overview
Eight perspectives help translate a large real-world association without treating diagnosis codes as a randomized exposure.

#### Bring Specifics to the Conversation

Tell your clinician what you use, how often, by which route, and for what reason.

Do not stop a GLP-1 medication or cannabis abruptly because of one observational report.

Lens takeaway
Specific exposure details support safer decisions.

#### Screen Beyond a Yes-or-No Question

Assess product, dose, route, frequency, impairment, co-use, and cannabis use disorder symptoms.

Integrate that history with cardiovascular, kidney, glycemic, and adherence risk.

Lens takeaway
The signal supports structured assessment.

#### Coding Can Select a Different Population

Repeated F12.x codes may capture clinically visible or problematic use more often than casual exposure.

That selection can contribute to outcome differences even after extensive matching.

Lens takeaway
Exposure misclassification may be clinically meaningful.

#### Residual Confounding Remains

Database studies cannot fully measure behavior, access, adherence, symptom burden, or every comorbidity.

E-values test robustness assumptions but do not prove that confounding is absent.

Lens takeaway
Sensitivity analysis strengthens, but does not causalize, an association.

#### A New Question About a High-Risk Population

Prior GLP-1 evidence focuses on therapeutic cardiovascular and kidney outcomes.

This paper adds cannabis-coded status as a potential marker of risk within treated diabetes care.

Lens takeaway
The contribution is patient-context risk stratification.

#### Optimize Established Risk Factors

Blood pressure, lipids, kidney monitoring, glycemic control, tobacco exposure, and adherence remain actionable.

Cannabis counseling should be added to those priorities, not substitute for them.

Lens takeaway
Act first on risks with proven interventions.

#### Measure Cannabis Exposure Directly

Prospective studies need product, dose, route, timing, biomarkers, and persistence data.

They should also measure why patients use cannabis and how that relates to illness burden.

Lens takeaway
Better exposure data are essential for causal inference.

#### Clinical Data Need Product Clarity

Cannabis labels and records often lack standardized exposure detail useful for research or care.

Improved documentation could make future safety evidence more specific and less stigmatizing.

Lens takeaway
Better data can improve both safety and fairness.

Join the Conversation

Have a question about how this applies to your situation? [Ask Dr. Caplan](https://benjamincaplan.com/ask-dr-caplan)

Want to discuss this topic with other patients and caregivers? [Join the forum discussion](https://cedclinic.com/interact/discussion-forums/)

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Source: [Cannabis use and cardiovascular, renal, and mortality outcomes in patients with type 2 diabetes receiving GLP-1 receptor agonists: A propensity score-matched cohort study.](https://pubmed.ncbi.nlm.nih.gov/42546368/)

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[GLP-1 Receptor Agonists: Safety and Clinical Evidence](https://cedclinic.com/glp-1-receptor-agonists-safety-profile-review/)

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[Review GLP-1 safety](https://cedclinic.com/glp-1-receptor-agonists-safety-profile-review/)

[GLP-1 Drugs: Cardiovascular Outcomes Clinical Evidence](https://cedclinic.com/glp-1-receptor-agonists-cardiovascular-outcomes-evidence/)
Background on cardiovascular outcome evidence for GLP-1 receptor agonists in metabolic care.

[Read cardiovascular context](https://cedclinic.com/glp-1-receptor-agonists-cardiovascular-outcomes-evidence/)

[Exploring Cardiovascular and Renal Benefits of GLP-1 Receptor Agonists](https://cedclinic.com/glp-1-receptor-agonists-cardiovascular-renal-benefits/)
A focused review of cardiovascular and kidney benefits that helps frame the new observational safety signal.

[Compare heart and kidney evidence](https://cedclinic.com/glp-1-receptor-agonists-cardiovascular-renal-benefits/)

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## Frequently Asked Questions

What kind of study was this?

It was a retrospective propensity score-matched cohort study using records from the TriNetX Research Network.

How many patients were compared?

The analysis matched 4,117 cannabis-coded patients with 4,117 comparison patients after identifying 614,333 eligible adults.

How was cannabis use defined?

Exposure required at least two ICD-10-CM F12.x cannabis-related diagnosis codes in the two years before GLP-1 therapy initiation.

What outcomes were associated with cannabis coding?

Cannabis coding was associated with higher all-cause mortality, major cardiovascular events, and major kidney events.

Does the study prove cannabis caused those outcomes?

No. The observational design can identify associations but cannot eliminate residual confounding or prove causation.

Did the study identify THC, CBD, dose, or route?

No. Diagnosis codes did not provide product, cannabinoid content, dose, route, frequency, or verified continued exposure.

Does cannabis cancel the benefits of GLP-1 therapy?

The study does not establish that conclusion. It compared outcomes within GLP-1-treated patients and did not randomize cannabis exposure.

Should patients stop a GLP-1 medication because of this paper?

No automatic change is supported. Patients should review the evidence, their cannabis exposure, and their overall risk with a clinician.

What should clinicians ask about?

Ask about product, dose, route, frequency, reason for use, impairment, tobacco and other substances, and cannabis use disorder symptoms.

What research is needed next?

Prospective studies should measure cannabis exposure directly and capture adherence, disease severity, co-use, reasons for use, and absolute event risks.

 

### Related

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).