The study, presented at NUTRITION 2026 by Dr Xiaowen Wang, investigated whether the health effects of plant-based diets differed according to their level of processing.

Dr Wang and team analysed dietary and health data from three long-running US cohort studies:

• Nurses’ Health Study (1984-2018)
• Nurses’ Health Study II (1991-2021)
• Health Professionals Follow-Up Study (1986-2020)

The analysis included 203,275 adults (160,690 women and 42,585 men) who were free from cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at baseline.

Researchers developed six plant-based diet indices that differentiated between healthy and unhealthy plant foods while also accounting for whether foods were ultra-processed (UPF) or non-ultra-processed.

Over the follow-up period, researchers documented:

• 26,209 cases of cardiovascular disease
• 21,006 cases of type 2 diabetes
• 55,493 deaths

Researchers found that overall diet quality was strongly associated with the risk of cardiovascular disease, type 2 diabetes and mortality.  Individuals following healthier dietary patterns – regardless of level of processing – experienced better health outcomes, while those consuming poorer-quality diets had higher cardiometabolic disease risks.

Notably, only the unhealthy ultra-processed plant-based diet pattern showed a statistically significant association with increased mortality risk.  Importantly, within healthy and unhealthy categories, the health risks were almost identical regardless of processing classification.

This study challenges the assumption that highly processed foods are inherently detrimental within plant-based eating patterns.  The findings suggest that the health benefits of a plant-based diet depend more on the nutritional quality of the foods chosen than on how processed they are.

This large prospective study indicates that healthy plant-based foods can support cardiometabolic health regardless of their level of processing, whereas poor-quality plant-based diets are associated with less favourable outcomes.

The therapeutic approach to obesity and type 2 diabetes mellitus (T2DM) is evolving in a similar way to how clinicians use antibiotics: targeting several pathways that often produce stronger and more durable effects than acting on a single pathway.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) laid the foundation, but the complexity of fat mass regulation quickly revealed the limits of one hormonal signal¹.

This has led to multi-hormonal agents that act simultaneously on glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin and/or peptide YY (PYY), better replicating the physiological and coordinated post-prandial response.

By engaging these pathways, the new therapies achieve broader and more synergistic metabolic improvements, marking a shift from single target drugs to integrated hormone-based treatment¹.

GLP-1–Based Therapies

GLP-1 is secreted by intestinal endocrine cells after nutrient ingestion.  It enhances glucose-dependent insulin secretion, slows gastric emptying, reduces appetite and promotes weight loss^1–5.

Central nervous system GLP-1 signalling within the hypothalamus and brainstem is central to regulating fat mass⁶.

Beyond glycaemia, GLP-1 exerts anti-inflammatory, endothelial and lipid-modulating effects¹.  Long-acting GLP-1RAs on their own such as semaglutide achieve substantial weight loss and glycaemic improvement, aided by gradual dose escalation strategies that improve tolerability¹.

Oral semaglutide represents a significant advancement, using SNAC (sodium N-(8-[2-hydroxybenzoyl] amino) caprylate) to overcome gastrointestinal degradation and enable systemic absorption, despite low bioavailability (~1%) and strict fasting administration requirements⁷.

Further innovations include small-molecule oral GLP-1RAs, such as orforglipron, which activate the GLP-1 receptor (GLP-1R) without peptide structures and offer simpler administration but without the same weight loss range^1,8-9.

GIP-Related Therapies

GIP is also released by different endocrine cells in the small intestine.  It stimulates insulin secretion during normoglycemia and influences lipid storage, though its metabolic effects are highly context-dependent¹.

Importantly, both GIP receptor (GIPR) agonism and GIPR antagonism have been shown to reduce body weight; an unexpected therapeutic paradox¹.  Central GIPR signalling suppresses appetite in rodents, while peripheral GIP actions vary with insulin sensitivity^1,10.

In humans, exogenous GIP shows limited appetite loss (anorectic) effects, suggesting species-specific physiological differences¹¹.

GLP-1/GIP Dual Agonists

Dual agonism of the GLP-1R and GIPR aims to capitalise on complementary hormonal effects.  Tirzepatide is the first approved dual GLP-1/GIP agonist and achieves greater weight loss and glycaemic improvement than semaglutide alone, suggesting synergistic incretin modulation¹².

Additional co-agonists, including SCO-094, VK2735, CT-388 and DR10627, are under development to refine receptor balance and broaden metabolic benefits¹.

Unimolecular GLP-1RAs/GIPR Antagonists

In contrast to co-agonists, unimolecular agents combining GLP-1R activation with GIPR blockade exploit evidence that GIPR antagonism enhances weight loss by disrupting adipogenic GIP signalling and amplifying GLP-1 driven satiety pathways¹.

Maridebart cafraglutide (formerly AMG-133) exemplifies this approach by merging GLP-1 agonism with a monoclonal GIPR-blocking antibody.  Monthly dosing produces meaningful body weight reductions (12–16%) and improves glycaemia in people with obesity and T2DM^1,13.

Pre-clinical work with the GIPR antagonist AT-7687 shows similar synergy when paired with GLP-1RAs¹.

Oxyntomodulin Physiology and -Based Therapies

Oxyntomodulin (OXM) is also secreted by the endocrine cells in the intestine but does not have a dedicated receptor.  Instead OXM binds to both the glucagon and GLP-1R¹⁴.

Glucagon as a standalone peptide is secreted by pancreatic alpha-cells.  It increases hepatic glycogenolysis and gluconeogenesis during fasting but also regulates satiety, enhances hepatic β-oxidation, reduces liver fat and increases energy expenditure^1,15.

OXM mimics many of these same effects when it binds the glucagon receptors¹⁴.  These metabolic properties support OXM use within multi-agonist therapies, without the risk of pure glucagon’s inherent hyperglycaemic potential.

OXM analogues (GLP-1/Glucagon Co-agonists)

Co-activation of GLP-1R and glucagon receptors leverages the anorectic and insulinotropic actions of GLP-1 with glucagon-driven increases in energy expenditure.  Survodutide and mazdutide are leading examples.

Survodutide has demonstrated up to 13–15% weight loss, alongside significant improvement in metabolic dysfunction–associated steatohepatitis (MASH)^1,16-17.

Mazdutide produces dose-dependent weight reduction and glycaemic improvement with good tolerability¹⁸.

Triple GIP/GLP-1/Glucagon Co-agonists

Retatrutide is a triple agonist that simultaneously activates GLP-1Rs, GIPRs and glucagon receptors.  This design aims to maximise appetite suppression and thermogenesis.

In phase 2 trials, retatrutide achieved approximately 17–18% weight loss in individuals with obesity without T2DM, surpassing most available pharmacotherapies^1,19.

Amylin Physiology and -Based Therapies 

Amylin is co-secreted with insulin and slows gastric emptying, suppresses glucagon and increases satiety through pathways distinct from other anorectic hormones ^1,20.  Long-acting analogues such as cagrilintide produce clinically significant weight loss²¹.

Amylin/GLP-1 Dual Agents

CagriSema, a fixed combination of semaglutide and cagrilintide that integrates GLP-1–mediated appetite suppression with amylin driven satiety and gastric emptying effects.  Recent trials show approximately 23% weight loss, exceeding either monotherapy or approaching metabolic surgery efficacy^1,21.

Peptide YY Physiology and Related Medicines

Peptide YY (PYY) is co-secreted with GLP-1 by endocrine cells in the intestine and converted to its active form PYY 3-36, which acts via Y2 receptors to inhibit neuropeptide Y (NPY) neurons and promote satiety^1,22.

After bariatric surgery, postprandial PYY, GLP-1 and OXM rises sharply and contributes to improved adipocyte mass regulation.  Early PYY analogues show reduced food intake and modest weight loss in short-term studies^1,22.

Table 1.  Comparison Table of Novel GLP-1–Based Medications

Conclusion

Together, these advances mark a decisive shift in obesity and T2DM therapeutics from a single pathway modulation toward integrated, multimodal hormone-based interventions.

GLP-1 remains the backbone, but layering complementary signals from GIP, glucagon, amylin and PYY allows for unprecedented degrees of weight reduction and metabolic restoration, as summarised for comparison in Table 1.

As uni-, dual- and triple-molecular agents continue to refine receptor balance, the field is rapidly approaching the efficacy once achievable only through metabolic surgery.

The emerging challenge is no longer whether we can produce profound metabolic benefits, but rather how to optimise durability, individualise receptor targeting and translate these complex pharmacologic innovations into long term clinical decision making.

This therapeutic evolution represents not merely incremental drug development, but a redefinition of how we conceptualise and treat the chronic diseases of obesity and type 2 diabetes.

Why do we see recommendations to reduce saturated fat intake, while at the same time see headlines from studies showing full-fat dairy may be healthy for us?

The answer lies in the fact that food can often be more than the sum of its parts.

Dairy, saturated fat & health

Dairy is a nutrient rich food group which has been championed for its role in bone, dental and muscle health for decades. On the contrary, dairy has also been the subject of ‘negative press’ concerning its saturated fat content, which is linked to heart disease and other metabolic complications. Cardiovascular disease (CVD) remains the number 1 cause of mortality globally, representing 31% of all deaths (1).

The effect of saturated fat on health has been hotly debated in recent years and the latest evidence review for Saturated Fat and Health from the UK Scientific Advisory Committee on Nutrition (August 1^st, 2019) recommends limiting saturated fat intake to ~10% of total calories (2). Saturated fat raises blood cholesterol levels, particularly low-density lipoprotein (LDL) cholesterol, which is a primary risk factor for cardiovascular disease.

At the same time, recent evidence from several large prospective cohort studies, systematic reviews and meta-analyses combining the results of thousands of subjects, have shown that milk and dairy foods, which can be high in saturated fat, have neutral or protective effects on cardiometabolic diseases (3-6).

These studies are having an impact on people’s beliefs of dairy. The idea that dairy fat is healthy is becoming more widespread among consumers. Bulletproof coffee, which encourages adding dairy fat to coffee specifically for potential health benefits, has grown into a successful lifestyle brand, and full-fat dairy is often encouraged as part of the ketogenic diet, one of the most popular diets in the world.

Whole milk and yoghurt have a saturated fat content of 2.3%, however cheese can range from 3-35% saturated fat which means that dairy is often targeted by public health bodies in efforts to reduce saturated fat intake. However, recent evidence has shown that cheese consumption does not raise LDL cholesterol compared to the same amount of fat from butter (7). This paradox may be due to a theory known as the ‘Dairy Matrix’. In reality, we eat whole foods rather than single nutrients. Dietary recommendations to reduce saturated fat do not distinguish between nutritionally poor ‘fried processed foods’ and nutritionally dense foods such as dairy.

How can a food high in saturated fat be healthy?

The Dairy Matrix: more than the sum of its parts

Dairy is a unique blend of nutrients including calcium, phosphorus, iodine, Vitamin B2 and B12, fermented cultures (yoghurt and cheese) bioactive peptides and high-quality protein containing all of the essential amino acids. Recently, scientists are considering the effects of milk and dairy foods on health beyond the benefits of the individual nutrients they contain. ‘The Dairy Matrix’ hypothesis suggests that the nutrients in dairy can interact with one another in ways that are beneficial for health (8).

Studies show that the dairy matrix has health benefits beyond the individual supplementation of the same nutrients and effective on cardiometabolic disease, weight management, bone mass density, bone metabolism, blood lipid levels and blood pressure (9).

Is cheese good or bad for heart health?

In relation to cheese, the explanation for the beneficial rather than harmful effects on cardiovascular diseases (CVD) might be due to interactions between components of the cheese matrix, including calcium, phosphorus, the milkfat globule membrane, and starter cultures, which together modify saturated fatty acid-induced increases in blood lipids. One thought is that these nutrients may block absorption of the saturated fats in cheese, but this has not been proven.

A 2018 study published in the American Journal of Clinical Nutrition examined the effects of dairy fat in cheese versus butter on markers of cardiometabolic health in 164 overweight volunteers. They consumed 40g dairy fat daily for 6 weeks, one group consumed the fat as cheddar cheese and another group consumed the fat as butter (matched for calcium and protein). Results indicated that dairy fat, eaten in the form of cheese, appears to differently affect blood lipids compared with the same constituents eaten in a butter matrix, with significantly lower total cholesterol observed when all nutrients are consumed within a cheese matrix (10). Observational studies have also shown that yoghurt and cheese consumption are linked to a reduce risk of diabetes (6, 8).

Dairy and bone health: more than just calcium?

Furthermore, the effects of milk and dairy foods on bone health may be due in part to positive interactions of calcium, protein and phosphorus with each other and with lactose and bioactive peptides in the dairy matrices, rather than simply a ‘calcium effect’ as is often assumed (11). Similarly, milk is a key element of the Dietary Approaches to Stop Hypertension (DASH) diet for preventing and treating blood pressure. This anti-hypertensive property is likely due to the combination of minerals and protein found in dairy. Moreover, a study examining the effects of cows’ milk, calcium fortified soy milk and calcium supplement on weight and body fat reduction in premenopausal overweight and obese women found that weight loss was greatest in subjects consuming milk compared to calcium matched soy drink and calcium supplements (12).

Emerging research on the dairy matrix and health

• Bioactive peptides present in milk are being investigated in relation to cardiometabolic health, immune health and (13).
• Fermented dairy contains bacteria with potential to produce short chain fatty acids in the gut which can have positive health benefits (14).
• Dairy fat has >400 fatty acids with different physiological properties. Milk fat globule membrane (MFGM) encloses the fatty acids and has shown potential benefits in relation to lipid metabolism (15)
• Dairy fat contains odd chain fatty acids C15 and C17 which cannot be synthesised by the body and are used as biomarkers of dairy intake. These fatty acids are contained in MFGM and may confer health benefits such as reduced risk of CVD and Type 2 Diabetes (16-17)
• Grass fed dairy products have higher levels of polyunsaturated fat Conjugated Linoleic acid which has shown potential benefits for cardiometabolic health. See link to our article about the Nutrition Benefits of Grass fed dairy.
• Food is complex in terms of its nutritional content and physical structure which can impact the digestion and metabolism of the nutrients. The structure of dairy products varies from the solid matrix of cheese, to the gel-like structure of yogurt, to liquid milk. Rates of gastric emptying can affect satiety and appetite.
• The matrix structure can also influence protein absorption. Casein consumed in a milk matrix is more slowly digested and absorbed than in supplement format, without an impact on muscle protein synthesis (18).

More research into the dairy matrix will allow us to fully understand the health benefits of dairy but current evidence indicates that dairy is a nutritious food group that contributes positively to overall health when eaten as part of a balanced diet.

In recent years, many people are choosing to reduce /remove dairy from their diet due to a variety of reasons such as veganism, taste preferences, intolerance, to promote animal welfare and environmental sustainability. However, removing dairy from the diet should be carefully considered as it is a major source of nutrients and significant efforts should be made to ensure the diet is nutritionally balanced. A registered Dietitian or Nutritionist can support with individualised advice for meeting dietary requirements.