Medications developed to control blood sugar are now at the center of a very different scientific story: how they might raise or lower the odds of developing cancer. As researchers follow millions of people taking these drugs, they are finding patterns that suggest some treatments could subtly fuel tumor growth while others may help hold it back. The emerging picture is complex, but it is already reshaping how I think about the next generation of diabetes and cancer care.
What is becoming clear is that the relationship between diabetes drugs and cancer is not a side note, it is a second act in the life of medicines that were once seen as purely metabolic. The same pathways that keep glucose in check also touch cell growth, inflammation, and the immune system, and that is where the surprising links are starting to appear.
Why diabetes and cancer keep showing up in the same patients
Before looking at specific drugs, I find it essential to understand why diabetes and cancer are so tightly intertwined in the first place. Large epidemiologic work has shown that Diabetes, particularly type 2, is associated with an increased incidence of several cancers, even after accounting for age and weight. One review noted in its Abstract that, Although the mortality attributable to cancer is lower than that from cardiovascular disease in this population, the signal is strong enough that oncologists and endocrinologists can no longer treat these conditions as separate worlds.
Mechanistically, chronic high insulin and glucose levels appear to be a major bridge between the two diseases. Hyperinsulinemia stands out as a major factor contributing to the association between DM and cancer, with modulation of circulating insulin and related growth signals emerging as a plausible way to influence tumor risk. A broader review of the Cancer and diabetes connection in the United States and the rest of the world concluded that the choice of glucose-lowering therapy can shift this hormonal environment in very different directions, which is why the Abstract and Background of that work call for closer scrutiny of specific medications.
Metformin, the workhorse drug that keeps turning up in cancer data
Among all diabetes drugs, Metformin has attracted the most attention for a possible protective effect against cancer. In one synthesis of case control work, Metformin use was associated with a lower incidence of liver cancer, with a reported relative risk of 0.54 and a confidence interval of 95% that stretched from 0.29 upward, a signal that is hard to ignore even if it does not yet prove causation. Earlier observational work that followed 8,000 people with diabetes treated with metformin also suggested lower cancer risk and mortality compared with those on other regimens, hinting that this old generic pill may be doing more than just nudging glucose down.
Researchers are now probing how this might work at the cellular level. A recent review described Metformin as a potential dual role player in oncology, influencing both tumor metabolism and the response to therapy, and used tools such as ROBINS and the RoB 2 tool to grade the risk of bias in observational and randomized studies. The authors concluded that evidence certainty fluctuated from moderate to low and stressed a need for large RCTs, a reminder that while the association between Metformin and lower cancer risk is intriguing, it is not yet a license to repurpose the drug as a stand alone anticancer agent outside clinical trials.
GLP‑1 receptor agonists: weight loss stars with an oncology subplot
Few drug classes have captured public attention like GLP‑1 receptor agonists, the GLP drugs behind brands such as Ozempic and Wegovy, and their rapid rise has drawn oncology researchers into the conversation. One large analysis of adults with obesity tracked the Outcomes of GLP‑1RA users by looking at the Incidence of 13 obesity related cancers, including bladder, colorectal, kidney, breast, endometrial, thyroid, pancreatic and others. Among 43,317 GLP‑1RA users, the investigators reported lower rates of several of these malignancies compared with matched controls, and the patterns were consistent across sensitivity analyses, suggesting that the effect was not simply an artifact of study design.
Another study presented as a target trial emulation used an observational study framework and reported that GLP‑1 receptor agonists might slightly reduce the risk of fourteen obesity related cancers in people with diabetes, particularly in women. The average BMI in that cohort was 38.5 kg/m2, underscoring that these were high risk patients in whom even modest shifts in cancer incidence could translate into thousands of avoided diagnoses over time. As one summary of the field put it, Studies of GLP‑1RAs in adults with diabetes and obesity now raise the possibility that these agents could lower the risk of obesity related cancers compared with some older drugs such as DPP‑4 inhibitors.
Sorting signal from noise on GLP‑1 safety, from thyroids to big pharma bets
As prescriptions for GLP drugs have surged, so have questions about long term safety, particularly around thyroid cancer. A large registry analysis compared GLP‑1 (short for Glucagon like peptide 1 receptor agonist) users with people taking SGLT2 inhibitors such as canagliflozin (Invokana), empagliflozin (Jardiance) or ertugliflozin (Steglatro), and did not find a major excess of thyroid malignancies in the GLP‑1 group. That kind of head to head comparison is important because it helps separate the effect of the drug from the underlying risk that comes with having diabetes and obesity in the first place.
At the same time, the commercial stakes around these molecules are enormous, and that is accelerating research. In one recent deal, Roche spent billions to acquire a company developing next generation GLP‑1 agents, with strategist Sourabh Nyalkalkar describing it as a “well timed move” that puts the company on par with incumbents in the GLP race. When that much capital is chasing a class of drugs, I expect oncology questions to be studied more, not less, because regulators and investors alike will want reassurance that the long term cancer profile of these agents is acceptable.
SGLT2 inhibitors: kidney and heart drugs that may touch tumor outcomes
Another modern diabetes class, the SGLT2 inhibitors, was initially embraced for kidney and heart protection, but researchers are now asking whether they also influence cancer risk. A recent analysis pooled randomized trials of SGLT inhibitors and concluded that overall and site specific cancer risk did not appear to be substantially increased, although the authors called for long term research to confirm that reassuring early picture. That kind of meta analysis is crucial because individual cardiovascular outcome trials are not powered to detect modest shifts in relatively rare cancers.
There are also hints that SGLT2 inhibitors might help some patients who already have cancer. In a preprint focused on gastrointestinal malignancies, investigators compared a cohort of GI cancer patients who received SGLT2i with a control group that did not, and reported differences in survival over a 5 year horizon, with the intervention cohort showing signals of benefit that they linked to metabolic effects and fewer deaths due to late stage diagnoses, according to the Jan report. Clinically, these drugs are already entrenched in diabetes care, with Commonly prescribed SGLT2 inhibitors including dapagliflozin (Farxiga), empagliflozin (Farxiga), and Jardiance, as well as canagliflozin (Invokana), and long term cardiovascular outcome data for agents like Jardiance have already been described as a feather in the cap for SGLT‑2 inhibitors.
Older drugs, new questions: thiazolidinediones and insulin analogues
While newer drugs grab headlines, older diabetes medications are also under scrutiny for their cancer footprints. A sweeping umbrella review that screened a total of 13,535 articles and ultimately included 87 high quality studies found mixed but important associations between different antidiabetic drugs and site specific cancers, including signals around insulin, sulfonylureas, and thiazolidinediones for breast cancer. The authors of that Oct analysis emphasized that After applying strict inclusion and exclusion criteria, the remaining evidence still pointed to meaningful differences between drug classes that clinicians should keep in mind when tailoring therapy.
Thiazolidinediones (TZDs) in particular have been studied as potential anticancer agents because of their effects on cell differentiation and metabolism. A detailed review of TZDs concluded that the results of these studies, while mixed, have fostered sufficient interest to stimulate the investigation of TZDs in clinical trials as anticancer agents, and that their use in combination regimens or in chemopreventive strategies merits further consideration, according to the Thiazolidinediones as anti cancer agents report. That kind of dual identity, as both a metabolic and potential oncology drug, is becoming a recurring theme across the diabetes pharmacopeia.
Rewriting cancer biology through metabolism: from Watson to lab benches
What ties many of these observations together is a renewed focus on cancer metabolism, the idea that tumors can be starved or slowed by changing how they use fuel. In a widely discussed lecture, Watson argued that cancer treatments could be refocused on targeting glycolytic metabolism, highlighting studies in highly glycolytic p53 deficient cancer cells that responded differently when their energy pathways were disrupted. That line of thinking dovetails with the way Metformin, SGLT2 inhibitors, and GLP‑1 agonists all tweak glucose handling, insulin levels, and sometimes even appetite and fat storage.
Newer work is pushing this concept into specific malignancies. A recent social media clip that drew 6521 likes and 29 comments highlighted Exciting work by Researchers at @CambridgeUniversity on a form of acute myeloid leukaemia (AML), showing how tweaking metabolic pathways can make blood cancer cells more vulnerable. In parallel, a feature on Medications used to treat type 2 diabetes described how these drugs may be doing more than managing blood sugar, they could also shape cancer biology in unexpected ways by altering insulin, inflammation, and other underlying biological processes, as summarized in a companion piece that noted that Diabetes drugs may be doing more than previously appreciated.
From population signals to bedside decisions
For patients and clinicians, the challenge is translating these complex, sometimes conflicting data into practical choices. A recent overview framed the issue bluntly, noting that Anti diabetic Drugs and Their Surprising Impact on Cancer Progression mean that people with Diabetes, particularly Type 2, may be at higher risk for cancer but also may benefit from carefully chosen regimens that tilt biology in their favor. That same report, published by Newswise, underscored that oncologists are beginning to ask not just whether a patient has diabetes, but which drug they are on, when planning treatment.
At the population level, comprehensive reviews of the role of diabetes medications suggest that no single agent is universally good or bad for cancer risk, and that shared risk factors such as obesity, inactivity, and aging complicate the picture. One synthesis of the literature on medications for diabetes and cancer concluded that while some drugs like Metformin appear to be associated with lower incidence of certain tumors and others raise concerns in specific organs, the most important step is to recognize that glucose lowering therapy is part of the cancer risk equation, not separate from it. For now, I see the smartest approach as one that pairs aggressive management of blood sugar with an equally deliberate eye on how each prescription might shape a patient’s long term cancer odds.
More from MorningOverview