Diabetes medications approved by the FDA are tested on carefully selected patient groups, but once they hit the market, they're used by far more diverse populations with different health conditions and backgrounds. This gap between clinical trial results and real-world effectiveness is forcing researchers and doctors to rethink how we understand whether diabetes treatments actually work for the people who need them most.

Why Do Clinical Trials Look So Different From Real Life?

When pharmaceutical companies design clinical trials to get FDA approval, they intentionally keep their study groups relatively homogeneous. This means excluding patients who are too old, too sick, or have multiple other health conditions. The reasoning is straightforward: a cleaner, simpler study population makes it easier to prove that a drug works and gets regulatory approval faster. However, this approach creates a significant problem once the drug reaches patients in hospitals, clinics, and pharmacies across the country .

David K. Ryan, a doctoral fellow at the Institute of Health Informatics and clinical pharmacology doctor at University College London, explained the disconnect: "It is often the case that the treatment dilemmas we face in the clinic do not align perfectly with the current evidence base. Frequently, there is a gap between what is studied in a randomized controlled trial and the decisions physicians must make in everyday clinical practice."

"It is often the case that the treatment dilemmas we face in the clinic do not align perfectly with the current evidence base. Frequently, there is a gap between what is studied in a randomized controlled trial and the decisions physicians must make in everyday clinical practice," said David K. Ryan.

David K. Ryan, Doctoral Fellow, Institute of Health Informatics and ST4 Doctor in Clinical Pharmacology and Therapeutics, University College London

One striking example illustrates this gap: Ryan's research examined the SGLT2 inhibitor empagliflozin, a medication that helps control blood glucose levels. In the original 2015 clinical trial that led to FDA approval, all participants had to have established cardiovascular disease. But when Ryan analyzed real-world prescribing data from 62,503 people with diabetes over eight years, he found something surprising: fewer than 20% of actual patients taking empagliflozin would have qualified for that original trial. In fact, 70% of real-world users did not have cardiovascular disease at all .

What Can Real-World Data Tell Us That Clinical Trials Cannot?

Real-world data comes from electronic medical records, pharmacy records, and nationwide health databases that capture how medications actually perform when used by diverse patient populations in everyday settings. This type of evidence can answer questions that traditional clinical trials never address .

Researchers have used real-world data to uncover several important findings about diabetes care:

• Medication Comparisons: Real-world studies showed that SGLT2 inhibitors perform better than metformin at preventing delirium, a serious confusion condition, in diabetes patients.
• Device Effectiveness: When researchers tracked 74,679 patients with type 2 diabetes who switched to continuous glucose monitors (CGMs), they found that users required fewer hospital visits and had better odds of reducing their A1C levels below 9, a key measure of long-term blood sugar control.
• Patient Behavior Patterns: Real-world data can explain why patients with diabetes stop, restart, and switch between GLP-1 receptor agonist medications and SGLT2 inhibitors, information that clinical trials cannot capture.
• Guideline Adherence: Studies can determine whether primary care physicians are actually prescribing medications according to current medical guidelines.
• Safety Signals: Real-world evidence countered FDA warnings about inhaled insulin and lung disease; analysis of millions of health records found only one case of pulmonary disease among 647 inhaled insulin users, compared to 27 cases of chronic obstructive pulmonary disease (COPD) among 1,830 controls.

Irl B. Hirsch, professor and diabetes treatment and teaching chair at the University of Washington School of Medicine, is a strong advocate for real-world evidence. "What you see in real-world evidence is something that pharma can do something about," he noted .

"What you see in real-world evidence is something that pharma can do something about," said Irl B. Hirsch.

Irl B. Hirsch, MD, Professor and Diabetes Treatment and Teaching Chair, University of Washington School of Medicine and UW Medicine Diabetes Institute

How to Bridge the Gap Between Trial Evidence and Your Treatment Plan

• Ask Your Doctor About Real-World Evidence: When your physician prescribes a diabetes medication, ask whether real-world data supports its use for your specific situation, especially if you have multiple health conditions or are older than typical trial participants.
• Discuss Your Individual Risk Factors: Share all your health conditions, medications, and concerns with your doctor so they can consider how a diabetes treatment might work for you specifically, not just for the idealized patients in clinical trials.
• Monitor Your Response Closely: Keep detailed records of how you respond to your diabetes medication, including blood sugar patterns, side effects, and any changes in your overall health, and share these observations with your healthcare team regularly.
• Advocate for Guideline-Based Care: If your doctor hasn't prescribed a medication that current guidelines recommend for your situation, ask why; real-world evidence shows that guideline-directed therapies improve outcomes when used consistently.

Are Disparities in Diabetes Care Being Overlooked?

Real-world data has also exposed troubling disparities in how diabetes medications are prescribed. A major study based on medical records from 590,000 people in Europe found that SGLT2 inhibitors, which help control blood glucose levels, were prescribed more frequently to men than women, to White people compared to other racial groups, and to people under 60 years of age .

These disparities are particularly concerning because real-world evidence confirms that these medications are effective across diverse populations. "We know from randomized controlled trials and accumulating real-world evidence that these drugs are effective, so it is important to address systemic barriers to ensure equitable access to evidence-based diabetes care," Ryan stated .

"We know from randomized controlled trials and accumulating real-world evidence that these drugs are effective, so it is important to address systemic barriers to ensure equitable access to evidence-based diabetes care," said David K. Ryan.

David K. Ryan, Doctoral Fellow, Institute of Health Informatics and ST4 Doctor in Clinical Pharmacology and Therapeutics, University College London

The challenge now is translating these real-world findings into actual changes in clinical practice. Doctors need to be aware of this evidence, and healthcare systems need to implement policies that ensure all patients, regardless of age, gender, or race, have access to the most effective diabetes treatments available .

As diabetes care continues to evolve, the message is clear: the medications that work in carefully controlled clinical trials can work even better in the real world when prescribed thoughtfully to diverse patient populations. Your doctor's job is to use both traditional trial evidence and real-world data to create a treatment plan tailored to your unique health situation.