By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv

What is CKM syndrome, and why does it change obesity treatment?

CKM syndrome reflects a quiet but profound revolution in medicine. In the past, doctors saw obesity, diabetes, heart disease and kidney disease as separate fields. Today, a new understanding is taking hold: these are links in a single biological chain. The body does not divide itself into medical specialties. Instead, the heart, kidneys, liver, blood vessels and metabolism work together, affect one another and sometimes fail together.

CKM syndrome is short for cardiovascular-kidney-metabolic syndrome. The American Heart Association defined it in an official advisory in October 2023. The definition covers the overlap between obesity, type 2 diabetes, chronic kidney disease and cardiovascular disease. According to the association, a third of adults in the United States have at least three risk factors for the syndrome.

The five stages of CKM syndrome

The association divided the syndrome into five stages. These stages help us understand where each patient stands and what the treatment goal is:

• Stage 0: no risk factors. The goal is prevention through healthy habits.
• Stage 1: excess body fat, abdominal obesity or prediabetes. The recommendation includes lifestyle changes and losing at least 5% of body weight.
• Stage 2: type 2 diabetes, high blood pressure, high blood lipids or kidney disease, but still no heart disease.
• Stage 3: early heart disease without symptoms, or a particularly high cardiac risk.
• Stage 4: heart disease with symptoms, alongside obesity, metabolic risk factors or kidney disease.

The clinical implications are dramatic. Treating obesity and diabetes is no longer just about weight or blood sugar. Rather, the goal is to prevent heart attacks, kidney failure, stroke and premature death.

The CVOT Summit: the studies changing the picture

This approach was at the center of the international CVOT Summit, held in November 2025. CVOTs are cardiovascular outcome trials, which test how drugs affect heart events and not just lab values. The summit report appeared in 2026 in the journal Cardiovascular Diabetology. It summarized the new studies along the cardiovascular-kidney-metabolic continuum.

Tirzepatide versus dulaglutide: the trial that changed the rules

One of the key trials in the report was SURPASS-CVOT. It is the first cardiovascular outcomes trial to compare two active drugs head to head, rather than against a placebo. The trial compared tirzepatide with dulaglutide in 13,165 people with diabetes and atherosclerotic heart disease.

A major cardiac event (cardiac death, heart attack or stroke) occurred in 12.2% of patients on tirzepatide, compared with 13.1% on dulaglutide. In other words, tirzepatide was no worse than a drug already proven to protect the heart, but it did not significantly outperform it either. In addition, it led to much greater drops in weight and blood sugar. According to the data presented, all-cause mortality was 16% lower with tirzepatide.

This brings us to one of the key insights of the new era. Large weight loss does not always translate automatically into a large drop in heart events. That is why the researchers suggest that the heart-protective mechanisms of GLP-1 drugs go beyond their effect on weight and sugar. Today, we see obesity not only as excess fat but also as an inflammatory, hormonal and vascular disease. You can read about the heart protection of semaglutide in my article on the SELECT trial.

Has the era of obesity pills arrived?

Part of the report focused on orforglipron, a GLP-1 agonist in pill form. Until recently, the most effective drugs came only as injections. The ATTAIN-1 trial enrolled 3,127 people with obesity and without diabetes. After 72 weeks, weight fell by 11.2% on the 36 mg dose, compared with 2.1% on placebo. Waist circumference, blood pressure and blood lipids also improved.

Since the report, things have moved fast. The US approved the drug in April 2026 under the name Foundayo, and it is also available in Israel, as I described in my article on Foundayo in Israel. Admittedly, the weight loss does not reach the strength of tirzepatide. Even so, a daily pill could greatly expand the number of patients willing to start treatment.

CKM syndrome and the kidneys: more than weight loss

One of the summit’s strongest messages was the shift from glucose-centered thinking to multi-system thinking. The CONFIDENCE trial tested a combination of finerenone and empagliflozin in people with diabetes and chronic kidney disease. After 180 days, the combination reduced urine albumin by 29% more than finerenone alone, and by 32% more than empagliflozin alone. Albumin in the urine is an early sign of kidney damage.

GLP-1 drugs protect the kidneys as well. In the FLOW trial, semaglutide reduced the risk of major kidney events by 24% in people with diabetes and kidney disease. This matters enormously. Chronic kidney disease is a silent and deadly complication of obesity and diabetes. Sometimes the patient feels perfectly fine until a very advanced stage. So the new approach aims to step in early, before irreversible damage occurs.

CKM syndrome: which tests are worth doing?

The practical message is simple. People living with obesity should check not only their weight and blood sugar, but also their heart and kidneys. A routine checkup can measure blood pressure, waist circumference, HbA1c (average blood sugar over the past three months) and a lipid profile. In addition, a urine test for albumin and a blood test for kidney function (eGFR) can detect kidney damage at an early stage. So ask your doctor to check all these measures together, and find out which stage of CKM syndrome you are in.

A new world of combination drugs

Another prominent theme in the report is the development of multi-hormone treatments. The first generation focused on GLP-1 alone. Today, researchers are developing drugs that combine additional mechanisms, such as GIP, glucagon, amylin and PYY. One example is retatrutide, which acts on three receptors.

The goal is not just greater weight loss. The researchers are aiming for a deep effect on inflammation, insulin resistance, liver fat, blood pressure, blood vessel function and cardiac risk. In fact, we are approaching an era in which obesity drugs will serve as a multi-system treatment to prevent metabolic aging.

Health organizations are changing their approach too

In December 2025, the World Health Organization issued its first global guideline on the use of GLP-1 medicines for treating obesity. The guideline gives a conditional recommendation for long-term use of these drugs in adults. At the same time, it recommends combining them with a behavioral program of diet and physical activity.

This is a historic step. For years, many people saw obesity as a problem of willpower. Today, official medical thinking views it as a chronic disease that requires long-term treatment, just like high blood pressure or diabetes.

CKM syndrome and the future: medicine for the whole person

Perhaps the most important message of the report is that cardiometabolic medicine is becoming integrative medicine. Today’s cardiologist understands the importance of liver fat. The nephrologist deals with obesity, and the endocrinologist thinks about stroke prevention. Meanwhile, the family doctor needs to see inflammation, sleep, stress, nutrition and physical activity as part of drug treatment.

Ultimately, CKM syndrome reminds us that the future is not about treating one disease at a time. The future is about seeing the person as a whole system, and that change has already begun.

The information in this article is general and does not replace personalized medical advice.

References

CVOT Summit Report 2025: advances along the cardiovascular-kidney-metabolic disease continuum

Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association

Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes

SURPASS-CVOT: Tirzepatide Bests Dulaglutide for Cardiovascular Protection

Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment

Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes

Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes

WHO issues global guideline on the use of GLP-1 medicines in treating obesity

SURPASS-CVOT and ATTAIN-1 were funded by Lilly, CONFIDENCE by Bayer, and FLOW by Novo Nordisk.