A groundbreaking discovery reveals that common diabetes drugs may hold the key to cancer prevention and treatment.
In the landscape of global health, two giants stand tall: diabetes and cancer. Individually, they represent significant public health challenges, but what happens when they intersect? Emerging research reveals a fascinating connection between the medications millions take to manage their diabetes and their risk of developing cancer. This discovery opens new avenues for cancer prevention and treatment, suggesting that the tools to fight one disease might unexpectedly help combat another.
With over 7.7% of adults worldwide expected to have diabetes by 2030, understanding medication impacts is crucial 1 .
Cancer diagnosis is projected to affect 20% of people globally during their lifetime 6 .
The implications are staggering—could the medicine used to control blood sugar today influence cancer risk tomorrow? This article explores the cutting-edge science behind this provocative question, examining how common diabetes medications might be our unexpected allies in the fight against cancer.
At first glance, diabetes and cancer might seem like unrelated conditions—one a metabolic disorder, the other characterized by uncontrolled cell growth. Yet decades of epidemiological evidence have revealed that people with diabetes have a significantly higher risk of developing certain cancers.
Source: Analysis of epidemiological studies 6
Diabetes and cancer share common ground in their origins. Both are influenced by aging, excess body weight, physical inactivity, poor diet, and smoking 1 . These overlapping risk factors create a perfect storm where one condition often accompanies the other.
Beyond external factors, internal biological processes create a direct link between diabetes and cancer:
High insulin levels, common in type 2 diabetes, can promote tumor growth by increasing the availability of insulin-like growth factor 1 (IGF-1), a potent cell growth stimulator 4 .
Diabetes creates a state of persistent, low-grade inflammation that can damage DNA and create an environment favorable to cancer development 1 .
High blood sugar provides abundant fuel for cancer cells, which famously consume glucose at accelerated rates—a phenomenon known as the Warburg effect 4 .
The plot thickens when we consider that diabetes medications themselves may modify cancer risk, either increasing or decreasing it depending on the drug class 6 . This revelation has launched an entirely new field of research, as scientists race to understand how these everyday medications might be repositioned as cancer prevention tools.
Comprehensive analysis of scientific studies has yielded fascinating patterns in how different diabetes medications affect cancer risk. A landmark systematic review published in 2023 analyzed 92 studies involving a staggering 171 million participants, providing the most complete picture to date of these relationships 6 7 .
The findings reveal that diabetes medications fall into three broad categories: those that appear protective against cancer, those that may increase risk, and those with mixed effects depending on cancer type.
Some diabetes medications demonstrate impressive associations with reduced cancer risk:
| Medication Class | Cancer Type | Risk Reduction | Significance |
|---|---|---|---|
| Biguanides (Metformin) | Colorectal | 15% lower risk | RR=0.85 6 7 |
| Biguanides (Metformin) | Liver | 45% lower risk | RR=0.55 6 7 |
| Thiazolidinediones | Breast | 13% lower risk | RR=0.87 6 7 |
| Thiazolidinediones | Lung | 23% lower risk | RR=0.77 6 7 |
| Thiazolidinediones | Liver | 17% lower risk | RR=0.83 6 7 |
| GLP-1 Agonists (Ozempic) | Multiple obesity-related cancers | Significant lower risk | 10 of 13 cancers studied |
Metformin's impressive protective effects, particularly for colorectal and liver cancers, may stem from its ability to lower insulin levels and reduce chronic inflammation 1 . Thiazolidinediones activate a pathway called PPARγ, which influences both fat metabolism and cancer cell behavior 2 . The newer GLP-1 agonists, which include drugs like Ozempic, show promise in "breaking the link between obesity and cancer" according to researchers .
On the other side of the spectrum, some diabetes medications associate with increased cancer risk:
| Medication Class | Cancer Type | Risk Increase | Significance |
|---|---|---|---|
| Insulin Secretagogues | Pancreatic | 26% higher risk | RR=1.26 6 7 |
| Insulins | Liver | 74% higher risk | RR=1.74 6 7 |
| Insulins | Pancreatic | 141% higher risk | RR=2.41 6 7 |
| Basal Insulins | Pancreatic | 49% higher risk (non-significant) | HR=1.49 5 |
These findings are particularly relevant for prescribing practices, especially for high-risk populations with diabetes 5 . The elevated risk associated with insulin and insulin secretagogues aligns with biological understanding—as growth-promoting hormones, they may potentially stimulate the growth of pre-existing cancer cells 1 .
Some medications display surprisingly complex relationships with cancer risk, appearing protective for some cancers while potentially harmful for others. Insulin, for instance, associates with lower risks of breast and prostate cancers even as it elevates risks for liver and pancreatic cancers 6 7 . This paradox highlights the complexity of cancer biology and the need for medication-specific, cancer-specific research.
While epidemiological studies reveal fascinating patterns, laboratory experiments show how we might harness these discoveries for innovative cancer treatments. A groundbreaking preclinical study published in September 2025 illustrates this potential perfectly, demonstrating how an old class of diabetes drugs might boost cutting-edge cancer therapy 2 .
Urothelial carcinoma (UC) is the second most common genitourinary cancer, causing over 16,000 deaths annually in the United States. The front-line treatment for metastatic UC is enfortumab vedotin (EV), an antibody-drug conjugate that targets a protein called NECTIN4 on bladder cancer cells 2 .
While EV initially shows strong response rates, treatment resistance often develops. The effectiveness of EV and similar therapies depends heavily on the level of the target protein—if cancer cells have low NECTIN4 expression, the treatment has less to attack.
Researchers at UCSF made a crucial discovery: the PPARγ pathway, which typically controls fat metabolism, also facilitates NECTIN4 expression 2 . This finding opened an exciting possibility—could they manipulate this pathway to increase NECTIN4 expression and make cancer cells more vulnerable to therapy?
The team turned to thiazolidinediones (rosiglitazone and pioglitazone), a class of diabetes medications known to stimulate PPARγ. Their hypothesis was simple yet revolutionary: these diabetes drugs might "prime" cancer cells for destruction by increasing their target expression.
Researchers first confirmed that NECTIN4 expression was highly variable in bladder cancer cells, explaining differences in treatment susceptibility 2 .
The team examined biopsies from patients before and after developing resistance to EV therapy, finding that most tumors still retained NECTIN4 expression, though at potentially insufficient levels 2 .
Scientists used thiazolidinediones to stimulate the PPARγ pathway in bladder cancer cells, successfully demonstrating increased NECTIN4 expression 2 .
The researchers combined this "priming" approach with NECTIN4-targeting CAR T-cell therapy, a sophisticated treatment that engineers a patient's own immune cells to attack cancer 2 .
The combination was tested in both cell lines and animal models to evaluate effectiveness 2 .
The findings were striking. By priming bladder cancer tumors with rosiglitazone, the researchers significantly increased the efficacy of NECTIN4 CAR T-cell therapy 2 . The diabetes medication had transformed less vulnerable cancer cells into better targets for immune therapy.
This approach worked in both treatment-naive settings and in cases where tumors had developed resistance to conventional NECTIN4-targeting therapy.
The research "lay[s] the groundwork for further CAR T cell development" and suggests drug combinations that could "expand the therapeutic window" of targeted cancer therapies 2 .
"By identifying and using a strategy to turn low-expressing tumors into higher-expressing tumors... we made the tumor cells more susceptible to NECTIN4-CAR T therapy." — Dr. Jonathan Chou, Senior Author 2
Behind these exciting discoveries lies a sophisticated array of research tools and methods. Here are some of the essential components in the diabetes-cancer research toolkit:
| Tool/Method | Function | Application Example |
|---|---|---|
| Large Healthcare Databases (CPRD, UK Biobank) | Provide real-world data on medication use and cancer outcomes | Population-based cohort studies on diabetes medications and pancreatic cancer risk 3 5 |
| Cancer Registries | Track cancer incidence and mortality in defined populations | Linking medication data to cancer outcomes in systematic reviews 3 6 |
| Cell Line Models | Allow laboratory study of cancer cell behavior under controlled conditions | Testing thiazolidinedione effects on NECTIN4 expression 2 |
| Animal Models | Enable study of cancer progression and treatment in living organisms | Evaluating CAR T-cell therapy efficacy after diabetes drug priming 2 |
| Systematic Review Methodology | Rigorously synthesize evidence from multiple studies | Comprehensive analysis of 92 studies on diabetes medications and cancer risk 6 7 |
| Time-varying Cox Proportional Hazards Models | Statistical analysis of time-to-event data | Calculating hazard ratios for pancreatic cancer risk with different diabetes medications 5 |
These tools have enabled researchers to move from initial observations to mechanistic understanding and therapeutic applications. Large databases provide the statistical power to detect patterns across millions of patients, while laboratory models allow scientists to uncover biological mechanisms and test innovative interventions.
Analysis of millions of patient records reveals patterns in medication effects.
Cell and animal models help uncover biological mechanisms behind observed effects.
Advanced statistical approaches account for confounding factors in observational data.
The fascinating intersection of diabetes treatment and cancer risk represents a paradigm shift in how we view these medications. They're not just blood sugar regulators—they're potential cancer prevention tools and therapy enhancers. The discovery that common diabetes medications can significantly influence cancer risk opens exciting possibilities for repurposing existing drugs for new therapeutic applications.
Understanding how different diabetes medications affect various cancer types will help clinicians tailor treatments for patients with diabetes, particularly those at high risk for specific cancers 5 .
The successful use of thiazolidinediones to enhance CAR T-cell therapy suggests a model for how other diabetes drugs might be repositioned as cancer treatment adjuvants 2 .
While more research is needed to fully understand the complexities of these relationships and translate them into clinical practice, the current evidence offers hope for innovative strategies to combat two of our most significant health challenges. As one researcher noted, this work "hold[s] promise in breaking the link between obesity and cancer" —a breakthrough that could benefit millions worldwide.
The conversation between diabetes and cancer research has begun, and it's revealing surprises that may transform how we prevent and treat both conditions for generations to come.