Mega Doctor News
By Roberto Hugo González
On March 1, 2025, healthcare professionals, students, and medical leaders gathered at the Renaissance Edinburg Conference Center for the DHR Health Obesity Summit—an event aimed at addressing the increasingly complex and overlapping challenges of obesity and diabetes. Attendees were given a rare opportunity to engage with leaders in the field of metabolic medicine. Among them was Dr. Ralph A. DeFronzo, a pioneer in diabetes research and treatment, known for his foundational work in defining the underlying causes of Type 2 Diabetes.
The summit served as an educational forum where new treatment guidelines, evolving research, and practical clinical approaches were presented and discussed. The central goal was to translate emerging evidence into actionable strategies that clinicians can use to improve patient outcomes, particularly among populations disproportionately affected by obesity and Type 2 Diabetes.
Dr. DeFronzo began his keynote address by making an important point: obesity and Type 2 Diabetes are biologically and clinically inseparable. In his words, “Obesity and diabetes go hand in hand,” and the absence of lean individuals with Type 2 Diabetes is becoming increasingly rare. His focus centered on what he calls “the pathophysiology-based treatment model”— a strategy that emphasizes understanding the root causes of disease over merely treating symptoms.
The core of Dr. DeFronzo’s presentation centered on a concept he introduced nearly four decades ago, known as “the Triumvirate.” This concept describes the three primary physiological defects in Type 2 Diabetes: insulin resistance in the liver, insulin resistance in muscle, and beta cell failure in the pancreas. However, this model has since evolved into what he now calls the “Ominous Octet,” a more comprehensive framework that adds five additional components: dysfunction in fat cells, the gastrointestinal tract, the alpha cells of the pancreas, the kidneys, and the brain.
Dr. DeFronzo walked the audience through each of these eight factors in detail. For example, he explained how fat cells, once overloaded, release free fatty acids into the bloodstream, worsening insulin resistance. He also highlighted the role of the gastrointestinal tract in producing hormones like GLP-1 and GIP, which help stimulate insulin but are less effective in people with Type 2 Diabetes due to cellular resistance.
One of the key takeaways from his talk was that long-term control of diabetes requires a multi-pronged approach. In his view, single-drug treatments are doomed to fail because they target only one or two of the eight underlying defects. Instead, he advocated for combination therapies that begin early in the disease course, focusing on long-term beta cell preservation and insulin sensitivity.
To support his recommendations, Dr. DeFronzo cited several landmark studies, including the UK Prospective Diabetes Study (UKPDS), the ADOPT study, and the more recent GRADE study. Each of these large-scale investigations examined the effectiveness of different medications in maintaining long-term glycemic control. They all pointed to a common conclusion: traditional treatments, such as metformin, sulfonylureas, and DPP-4 inhibitors, are insufficient over time. “If you think stepwise therapy with these drugs is going to work, you’re delusional,” he stated candidly.
Despite metformin being one of the most prescribed diabetes medications in the U.S., Dr. DeFronzo argued that it only addresses hepatic glucose production and fails to protect beta cells or improve muscle insulin resistance. Sulfonylureas, he added, may work briefly by forcing the pancreas to release insulin, but they accelerate beta cell failure. DPP-4 inhibitors, meanwhile, offer minimal efficacy and do not meaningfully influence long-term outcomes.
In contrast, he spoke highly of thiazolidinediones (TZDs), particularly pioglitazone. These medications not only improve insulin sensitivity in muscle, liver, and fat but also help preserve beta cell function. He emphasized their long-term efficacy, cardiovascular benefits, and cost-effectiveness— pioglitazone, for instance, can cost as little as $5 per month. He pointed to multiple studies that demonstrated durable glycemic control with TZDs, as well as evidence supporting their positive impact on cardiovascular health and liver fat (NAFLD/NASH).
However, the most promising class of drugs, in Dr. DeFronzo’s view, are the GLP-1 receptor agonists and the newer dual agonists like tirzepatide. These drugs offer comprehensive benefits: they stimulate insulin secretion in a glucose-dependent manner, reduce glucagon levels, suppress hepatic glucose production, promote weight loss by acting on appetite-regulating centers in the brain, and help protect beta cell function. Unlike sulfonylureas, these agents do not cause hypoglycemia because blood glucose levels modulate their activity.
He particularly praised tirzepatide for its superior efficacy in both glycemic control and weight loss. In head-to-head studies against semaglutide, tirzepatide achieved greater reductions in A1C and led to an average weight loss of approximately 20–25% in non-diabetic obese individuals, comparable to the results seen with bariatric surgery. He noted that future iterations of these drugs, such as IcoSema and CagriSema, are likely to offer even more potent effects.
Yet, cost remains a significant barrier. These medications often exceed $1,000 per month, putting them out of reach for many patients. Dr. DeFronzo acknowledged this challenge but stressed that clinicians must understand which therapies are most effective, so that if and when cost barriers are resolved through policy changes, insurance coverage, or the introduction of generics, clinicians are already equipped to deliver optimal care.
Another central theme of his talk was the importance of early intervention. He emphasized that waiting for treatment failure before escalating therapy is a flawed approach. By the time many patients receive intensive treatment, substantial and irreversible damage to beta cells has already occurred. Instead, he argued, aggressive combination therapy should be initiated at diagnosis— or even earlier, in the pre-diabetes stage— when beta cells are still functional.
Beyond pharmacology, Dr. DeFronzo touched on lifestyle interventions. While he acknowledged their value, he was also frank about their limitations. “Over 200 studies have shown that long-term success with diet and exercise alone is rare,” he said. “If your patient doesn’t gain weight, that’s a win. If they lose weight and keep it off, that’s a miracle.” This realistic perspective was well-received by the audience, who appreciated his balance of scientific rigor and clinical pragmatism.
The DHR Health Obesity Summit as a whole served as a vital educational experience for all attendees. By bringing together top-tier speakers, interactive discussions, and cutting-edge science, it provided healthcare professionals with the tools they need to confront two of the most pressing public health issues of our time: obesity and Type 2 Diabetes.
Dr. DeFronzo’s presentation stood out not only for its depth of content but also for its clarity. His combination of humor, clinical insights, and a relentless focus on what works— and what doesn’t— left a lasting impression. He reminded the audience that while the science of obesity and diabetes is complex, the principles of effective treatment are straightforward when grounded in pathophysiology.
In sum, the DHR Health 2025 Obesity Summit offered more than just continuing education credits. It delivered a perspective on how to treat patients more effectively and equitably in an era of evolving science and shifting clinical expectations. For those who attended, it was a chance to learn from the best— and bring that knowledge back to their practices to improve lives across the Rio Grande Valley.
See related story:
