The scale showed similar weight loss across all three diets, but the liver responded very differently.

Losing weight may improve metabolic health regardless of the diet used—but a recent randomized controlled trial suggests that what people eat could influence which metabolic benefits they see, even when weight loss is similar.

Published in Cell Metabolism, the study found that people with metabolically unhealthy obesity who lost about 10% of their body weight experienced improvements in insulin sensitivity across three different diets. However, those following a very-low-carbohydrate ketogenic diet (KD) showed substantially greater improvements in several measures of liver health and glucose metabolism than participants following either a Mediterranean diet or a very-low-fat, plant-forward diet.

The findings could have implications for dietary strategies aimed at people with obesity accompanied by conditions such as prediabetes and excess liver fat, although larger studies are needed before drawing firm conclusions.

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Why diet composition may matter

Obesity is closely linked with metabolic problems including prediabetes, abnormal blood lipids, insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD).

Weight loss itself can improve many of these conditions. But researchers have increasingly questioned whether the composition of a diet can produce additional metabolic effects beyond simply reducing body weight.

Previous nutrition studies have often struggled to answer that question because participants don’t always follow their assigned diets closely, and different diets can produce different amounts of weight loss. If one group loses substantially more weight, it becomes difficult to determine whether its metabolic improvements came from the diet itself or from the greater weight reduction.

The new trial attempted to address this issue by comparing three diets while aiming for a similar degree of weight loss.

Inside the study

Researchers randomized 55 adults with metabolically unhealthy obesity—defined in the study as obesity accompanied by prediabetes and hepatic steatosis—to one of three dietary approaches:

Ketogenic diet: very low in carbohydrates
Mediterranean diet: based on the Mediterranean dietary pattern
Plant-forward diet: very low in fat and emphasizing plant foods

Participants followed their assigned diets for approximately five months and were asked to lose around 10% of their starting body weight.

Of the 55 people randomized, 42 completed the study and were included in the main analysis. Each final diet group included five men and nine women, with an average age of about 43 years and an initial BMI close to 39 kg/m².

To maximize adherence, researchers supplied the study food and conducted weekly consultations with dietitians. Participants logged more than 95% of their meals and snacks as consumed.

The researchers examined a broad range of outcomes, including insulin sensitivity, liver fat, glucose control, pancreatic beta-cell function, blood lipids, hormones and blood pressure.

Weight loss was similar—but metabolic changes weren’t

Across all three groups, losing approximately 10% of body weight produced a major improvement in skeletal-muscle insulin sensitivity, which increased by nearly 50%.

Liver insulin sensitivity also improved across the diets. But the magnitude of the improvement was notably greater among participants following the ketogenic diet—roughly two to three times greater than the changes seen with the Mediterranean and plant-forward diets.

The biggest difference emerged in the liver.

Liver fat fell substantially more with keto

All three diets reduced hepatic triglyceride content, but the reduction was considerably larger in the ketogenic group.

Ketogenic diet: liver triglycerides fell by about 67%
Mediterranean and plant-forward diets: reductions were approximately 45%

The ketogenic diet was also associated with a greater reduction in hepatic de novo lipogenesis—the process through which the liver creates new fat.

These findings suggest that achieving the same amount of weight loss does not necessarily produce identical changes in liver metabolism.

Glucose and insulin responses also favored keto

The ketogenic group experienced the largest reduction in 24-hour plasma glucose exposure, which fell by approximately 20%, compared with around 8% in the other two groups.

Twenty-four-hour insulin exposure decreased in all groups as well, but the difference was striking:

Ketogenic diet: approximately 74% reduction
Mediterranean diet: approximately 44% reduction
Plant-forward diet: approximately 27% reduction

Insulin clearance—the rate at which the body removes insulin from circulation—also increased most in the ketogenic group.

Several other measures of metabolic health showed similar patterns. Fasting glucose and insulin, very-low-density lipoprotein particle size and the lipoprotein-insulin resistance index all improved most among ketogenic-diet participants.

The Matsuda index, a measure of whole-body insulin sensitivity, improved across all three diets, with a larger increase in the ketogenic group than in the Mediterranean group.

HbA1c also declined more with the ketogenic diet.

Prediabetes remission was more common with keto

The researchers reported that 50% of participants in the ketogenic group achieved remission of prediabetes, compared with:

29% in the Mediterranean group
7% in the plant-forward group

That result is potentially important, but it needs to be interpreted cautiously. The study was relatively small, and outcomes other than the two primary insulin-sensitivity measures were considered exploratory and were not adjusted for multiple comparisons.

In other words, these findings are promising but aren’t sufficient to establish that a ketogenic diet is superior for preventing diabetes or reducing long-term cardiovascular risk.

What happened to cholesterol and triglycerides?

Not every metabolic marker favored one diet.

Measures including LDL cholesterol, apolipoprotein B and 24-hour plasma triglycerides did not differ significantly between the diets.

This is an important distinction. The ketogenic diet produced larger improvements in several measures of glucose regulation and liver metabolism, but that does not mean it improved every aspect of cardiometabolic health more effectively.

Other biological changes

The ketogenic diet was also associated with several additional changes.

Participants following the diet experienced increases in estimated glomerular filtration rate (eGFR) and reductions in cystatin C, TNF-α and plasminogen activator inhibitor-1.

Urinary 8-isoprostane, a marker associated with oxidative stress, also decreased in the ketogenic group but not in the other two groups.

Researchers additionally observed differences in nitrogen excretion and hormone levels. Urinary nitrogen increased among ketogenic-diet participants, while it decreased in the Mediterranean and plant-forward groups.

Plasma glucagon increased by about 52% with the ketogenic diet but fell by roughly 30–40% in the other groups. Consequently, the glucagon-to-insulin ratio increased more than threefold in the ketogenic group.

No serious adverse events were reported in any of the three groups.

What does the study actually tell us?

The most interesting message isn’t simply that “keto causes more weight loss.” The participants were studied after achieving a similar target of approximately 10% weight loss.

Instead, the findings raise the possibility that macronutrient composition influences how the body responds to weight loss.

All three diets improved insulin sensitivity and reduced liver fat. But the ketogenic diet was associated with particularly large changes in:

Liver fat
Hepatic insulin sensitivity
Glucose exposure
Circulating insulin
Hepatic fat production
Several markers of metabolic dysfunction
Prediabetes remission

That makes the liver findings especially noteworthy. The scale may tell us that two people have lost a similar amount of weight, while their underlying metabolic responses can look quite different.

Important limitations

The results shouldn’t be interpreted as proof that a ketogenic diet is universally better than a Mediterranean or plant-forward diet.

The study had a small sample size, with only 42 participants completing the intervention. The trial also focused on a specific population—people with obesity, prediabetes and fatty liver—so the findings may not apply to people without these conditions.

Most importantly, many of the reported outcomes were exploratory. The researchers did not adjust those outcomes for multiple statistical comparisons, increasing the possibility that some observed differences could have occurred by chance.

The study also cannot establish whether less restrictive carbohydrate reduction that doesn’t produce ketosis would generate similar benefits. Nor does it answer whether the liver improvements would persist if participants adopted the ketogenic diet while maintaining, rather than losing, weight.

Finally, improved biomarkers don’t automatically translate into fewer heart attacks, strokes, cases of diabetes or other long-term health outcomes.

The bottom line

This trial adds to evidence that weight loss and diet composition may influence metabolic health in partly independent ways.

Losing about 10% of body weight improved insulin sensitivity across all three diets. But the very-low-carbohydrate ketogenic diet produced substantially larger improvements in liver fat, hepatic insulin sensitivity, glucose exposure and several other metabolic measures.

The results are intriguing, particularly for people with obesity, prediabetes and fatty liver. But they are best viewed as a signal for further research rather than a definitive verdict on the best diet.

Larger and longer trials will be needed to determine whether the metabolic advantages observed with a ketogenic diet translate into meaningful reductions in diabetes and cardiovascular disease—and whether similar benefits can be achieved with less restrictive approaches.