Introduction
Living to age 90 and beyond—what researchers call exceptional longevity—remains a major focus of aging and health research. A new study published in the The Journals of Gerontology: Series A (DOI: 10.1093/gerona/glaf095) explores whether the widely-used diabetes drug Metformin, when started by post-menopausal women with type 2 diabetes, is associated with higher odds of reaching age 90 compared to another class of diabetes drugs. PubMed+2ScienceAlert+2
In this article we’ll break down the study’s design, findings, implications, mechanisms under consideration, limitations, and what this might mean for future aging/geroscience research.
What the Study Did — Study Design & Cohort
The primary paper, “Comparative Effectiveness of Metformin Versus Sulfonylureas on Exceptional Longevity in Women With Type 2 Diabetes: Target Trial Emulation,” by Shadyab et al., used a “target trial emulation” framework among participants in the Women’s Health Initiative (WHI) cohort. PubMed
Key design features:
The study identified women aged ≥ 60 years from the WHI with incident type 2 diabetes (i.e., newly diagnosed, no prior hypoglycemic agents or insulin) who initiated either metformin monotherapy or sulfonylurea monotherapy. PubMed+1
They matched 1:1 via propensity scores on demographics, lifestyle behaviors, diabetes duration, comorbidities (hypertension, cardiovascular disease, COPD, cancer), body-mass index, and concomitant medications to balance treatment groups. PubMed
The endpoint: survival to age 90 (i.e., avoid death before age 90). They followed women from treatment initiation until death before 90, turning age 90, last contact, or Feb 17 2024. PubMed
Among 438 matched women (219 metformin initiators, 219 sulfonylurea initiators), they compared incidence rates of death before age 90. PubMed
Findings:
Incidence rate of death before age 90: 3.7 deaths per 100 person-years (95% CI: 3.1-4.4) for metformin initiators vs. 5.0 deaths per 100 person-years (95% CI: 4.2-5.8) for sulfonylurea initiators. PubMed+1
Adjusted hazard ratio (HR) for death before age 90 for metformin vs sulfonylurea: 0.70 (95% CI: 0.56-0.88). That is, ~30% lower risk. PubMed
The authors conclude: “In this first target-trial emulation… we found that metformin initiation increased exceptional longevity compared with sulfonylurea initiation among women with type 2 diabetes.” OUP Academic+1
Why This Study Matters — Context & Significance
The idea of gerotherapeutics—drugs repurposed to target the biology of aging (rather than just diseases)—is gaining traction. Metformin is one of the most investigated candidates because it is inexpensive, widely used, and has an established safety profile. Technology Networks+1
Previous observational data hinted that metformin users have lower mortality than non-users (even adjusting for diabetes). However, previous studies seldom employed rigorous matching or emulated a trial, especially with the explicit endpoint of survival to age 90. This study adds new rigour.
For women with type 2 diabetes—a population at elevated risk of cardiovascular disease, cancer, and other age-related morbidities—finding that one commonly used drug may confer additional survival benefit is notable.
It opens up further research into whether the benefit is due to improved diabetes control, fewer complications, or direct effects on aging processes (mitochondria, inflammation, cellular senescence, etc.).
Potential Mechanisms — How Metformin Might Influence Longevity
Although this study did not probe mechanisms, the authors and prior literature suggest several plausible biological pathways by which metformin could influence longevity:
AMPK activation / mitochondrial effects: Metformin is known to inhibit mitochondrial complex I, activate AMP-activated protein kinase (AMPK), leading to improved cellular energy balance, reduced reactive oxygen species (ROS) production, and enhanced metabolic stress resilience. Wikipedia+1
Reduced insulin/IGF-1 signalling: Some longevity models in animals tie reduced insulin/IGF-1 signalling to lifespan extension; metformin’s insulin-sensitising effects may contribute.
Reduced chronic inflammation: Low-grade systemic inflammation (“inflammaging”) is a hallmark of aging; metformin may dampen inflammatory mediators.
Cellular senescence / DNA damage protection: Some observational studies suggest metformin limits DNA damage, improves DNA repair, reduces accumulation of senescent cells. ScienceAlert+1
Modulation of metabolic/gut-microbiome interaction: Emerging research shows metformin alters the gut microbiome, with downstream effects on metabolism and possibly aging-relevant pathways. Wikipedia
Mimicking caloric restriction: Because caloric restriction is one of the most robust lifestyle interventions for lifespan extension in multiple species, the notion that metformin acts as a pharmacologic “exercise/CR mimetic” has been floated. Wikipedia
Thus, while improved glycaemic control and fewer complications in diabetes likely contribute, the notion that metformin has pleiotropic effects beyond glucose regulation is central to its candidacy as an “anti-aging” therapeutic.
Limitations & Important Caveats
No study is without nuance. Key limitations of this work include:
Observational design: Despite the target-trial emulation and matching, this is not a randomized controlled trial (RCT). The authors emphasize that causality cannot be inferred. PubMed+1
Active comparator only: The comparison was metformin versus sulfonylurea monotherapy—not versus no treatment or versus healthy non-diabetic women. Therefore, the observed survival benefit could in part reflect differences in the underlying treatments, patient selection, or unmeasured confounders (e.g., severity of diabetes, treatment adherence, kidney/liver function).
Women only: The cohort comprises post-menopausal women from the WHI, so the findings may not generalize to men, younger individuals, or non-diabetic populations. New Atlas
Sample size: Although the matching produced 438 women, this is still moderate in size, and the event of reaching age 90 is relatively rare—limiting precision.
Residual confounding: Propensity score matching balances measured covariates, but unmeasured variables (e.g., socio-economic status, genetic longevity factors, subclinical health conditions) might still influence the outcomes.
Treatment initiation bias: The study considered women initiating therapy at age ≥ 60; earlier diabetes duration, prior untreated hyperglycaemia, or differential healthcare access could impact survival.
Endpoint of survival to age 90: Using age 90 as threshold for “exceptional longevity” is useful but somewhat arbitrary; survival beyond age 90 is influenced by many genetics/lifestyle factors outside medication effects.
Mechanistic ambiguity: The study doesn’t establish how metformin might extend longevity—only an association.
The authors themselves caution: “Because this comparison was not made to placebo in a randomized controlled trial and given the observational design with potential for residual confounding, causality cannot be inferred.” PubMed
Implications & What It Means for Practice and Research
For clinical practice:
It’s too early to recommend metformin solely as a longevity drug for women without diabetes. The study is suggestive but not definitive.
However, in women with type 2 diabetes who are candidates for metformin (and not contraindicated), this adds an extra possible benefit to choosing metformin over sulfonylureas (where clinically appropriate).
Clinicians should continue to tailor diabetes treatment per guidelines (e.g., first-line metformin barring contraindications, lifestyle interventions, etc.).
Awareness of aging/geroscience perspectives is growing—but until RCTs confirm effects, medication choices should prioritize established outcomes (glycaemic control, complication prevention, cardiovascular risk) rather than speculative longevity.
For research and drug development:
This work strengthens the case for metformin as a candidate gerotherapeutic and supports further investigation into aging-modulating drugs in humans.
The “target-trial emulation” methodology helps strengthen inference from observational data — usefully bridging between large cohort data and expensive, long-duration RCTs.
Future research priorities include:
RCTs comparing metformin versus placebo (or versus other agents) in broader populations (including men, non-diabetic individuals, younger adults) with endpoints of health-span and lifespan.
Mechanistic studies—identifying which aging pathways (e.g., inflammation, mitochondrial function, senescence) are modified in humans by metformin.
Biomarker studies—identifying whether metformin initiators show slower “biological age” progression (e.g., via epigenetic clocks, telomere attrition, proteomic/metabolomic signatures).
Safety/long-term hydration/renal monitoring in older individuals, given that some older women might have comorbidities affecting drug metabolism/excretion.
For public health & aging policy:
If metformin (or similar agents) truly enable a meaningful increase in healthy lifespan, the implications for healthcare systems, pension planning, and aging populations are substantial.
However, ethical and practical issues remain: Who should receive gerotherapeutic drugs? At what age/dose? With what monitoring?
Ensuring access, avoiding off‐label misuse, and maintaining rigorous safety surveillance are paramount.
Real-World Use-Case Scenarios
A 65-year-old post-menopausal woman newly diagnosed with type 2 diabetes
– She is overweight, has hypertension, normal renal function.
– Initiating metformin (as first-line) aligns with guidelines and (if the study findings hold) may confer a higher likelihood of reaching age 90 compared to choosing a sulfonylurea.
– The clinician monitors HbA1c, kidney function, vitamin B12 levels (metformin may reduce B12 absorption).
– Lifestyle interventions remain foundational (diet, exercise, weight management). Medication isn’t a substitute.
A 72-year-old woman with type 2 diabetes and moderate chronic kidney disease (eGFR ~ 45 mL/min/1.73 m²)
– Choice of diabetes medication must carefully weigh renal safety. Metformin might be contraindicated or require dose‐adjustment depending on guidelines.
– This study’s findings highlight potential extra benefit, but safety comes first.
A non-diabetic woman interested in longevity interventions
– Some media articles may suggest “metformin for longevity.” However, the study applies to women with diabetes initiating metformin vs sulfonylurea—not to healthy non-diabetics initiating metformin.
– Off-label use of metformin for “anti-aging” remains speculative and should only be considered in clinical trial settings. The authors emphasise the lack of causation proof. New Atlas
How This Fits Into the Latest Trends in Aging & Medicine
The field of geroscience (studying aging mechanisms and interventions) is growing rapidly. Drugs like metformin, rapamycin/rapalogs, senolytics (drugs to clear senescent cells), NAD+ precursors, and others are under intense investigation.
This study reflects a trend: leveraging large, long-term cohorts (like WHI) and sophisticated statistical methods (matching, target-trial emulation) to infer potential effects on lifespan/health-span — bridging the gap between shorter clinical trials and the long timeline of aging research.
Precision aging: There's increasing interest in identifying which subgroups (by sex, genetics, comorbidity burden) may derive greatest benefit from gerotherapeutics. This study highlights women, but further work will clarify broader generalisability.
Biomarkers of aging: While this study uses age 90 survival as a “hard” endpoint, many future studies will use intermediate biomarkers (epigenetic clocks, proteomics, etc.) for earlier readouts of anti‐aging interventions.
Ethical/regulatory: The more aging is seen as a “treatable medical condition,” the more regulatory frameworks must adapt (e.g., trial design, endpoints, reimbursement). Studies like this help build evidence base for such shifts.
Key Takeaways
In a well-matched cohort of post-menopausal women with type 2 diabetes, initiating metformin monotherapy (vs sulfonylurea) was associated with ~30% lower risk of death before age 90 (HR≈0.70). PubMed+1
The findings are intriguing and align with the broader hypothesis that metformin has geroprotective effects, but causality cannot yet be concluded.
For women with diabetes, this provides an additional rationale (beyond glucose control) to consider metformin as a first-line therapy if not contraindicated—but this does not yet translate into prescribing metformin for non-diabetics purely for longevity.
Future RCTs and mechanistic studies are needed to confirm whether metformin truly delays aging and improves survival independent of diabetes control.
The study underscores the importance of treating aging-related decline as a targetable process, not just disease by disease.
What Should You Do? (From a Health/Aging Perspective)
If you are a clinician, patient, or informed health-consumer:
For those with type 2 diabetes: continue to follow guideline-based treatments (including lifestyle first, then pharmacotherapy). Discuss with your provider whether metformin is the best first-line agent for you (often it is) and monitor as appropriate (renal function, B12, etc.).
For those without diabetes: don’t interpret this study as a green light to take metformin for “anti-aging” outside of clinical trials. The evidence is promising but preliminary.
For all healthy-aging efforts: continue focusing on proven interventions — e.g., maintaining healthy weight, regular aerobic and resistance exercise, adequate sleep, healthy diet (e.g., Mediterranean or plant-rich), smoking cessation, stress management. Medication should complement, not replace, lifestyle.
Stay informed: As geroscience advances, new trials and evidence will emerge. This is an exciting area but still evolving.
Concluding Thoughts
The study by Shadyab et al. offers compelling evidence linking metformin initiation to increased likelihood of reaching age 90 among women with type 2 diabetes. While we must interpret with caution (given observational design and specific population), the results add meaningful weight to the notion of metformin as a potential gerotherapeutic.
In the broader narrative of aging research, this work exemplifies how large-scale cohort data, rigorous matching methods, and long-term follow-up can provide actionable insights ahead of (or in parallel with) standard RCTs.
Ultimately, whether metformin—or other drugs—will become mainstream “longevity therapeutics” remains to be seen. But for now, this study offers both hope and a roadmap for future investigation.
References:
Shadyab AH, Espeland MA, Odegaard AO, et al. Comparative Effectiveness of Metformin Versus Sulfonylureas on Exceptional Longevity in Women With Type 2 Diabetes: Target Trial Emulation. J Gerontol A Biol Sci Med Sci. 2025;80(7):glaf095. doi:10.1093/gerona/glaf095. PubMed+1
ScienceAlert: “Common Diabetes Drug Linked to ‘Exceptional Longevity’ in Women.” June 6 2025. ScienceAlert
New Atlas: “Common diabetes drug associated with ‘exceptional longevity’.” May 24 2025. New Atlas
