1Associate Professor, department of Pharmacology, Shree Venkateshwara college of Paramedical Science Gobi-638455, Erode (DT), Tamil Nadu Affiliated to The Tamil Nadu Dr. MGR Medical University, Chennai.
2Department of Pharmacology, Shree Venkateshwara College of Paramedical Science Gobi-638455, Erode (DT), Tamil Nadu Affiliated to The Tamil Nadu Dr. MGR Medical University, Chennai
Obesity, which refers to the state of excessive body fat accumulation owing to an imbalance between energy intake and expenditure, is a major risk factor for non-communicable diseases, such as type 2, diabetes mellitus, dyslipidaemia, cardiovascular diseases, stroke, and some cancers. the world health organization(who)defined obesity is major public health problem in 1997. Lifestyle modification such as diet and exercise intervention is essential both prevention and management of obesity, and pharmacotherapy may be considered if the interventions are ineffective for individuals with a body mass index [bmi] ≥30 kg/M OR FOR THOSE WITH bmi ≥27kg/m when co-morbidities, such as hypertension or type 2 diabetes mellitus are present. However, anti-obesity drugs are a frequent adjunct because these interventions have limited long term success and the weight is regained when treatment is discontinued. Many modifications have been used to manage obesity over the years. However, most of the anti-obesity drugs that were approved and marketed have now been withdrawn due to serious adverse effects. In the 1990s, fenfluramine and dexfenfluramine were withdrawn from the market because of heart valve damage. In 2000, the European medicines agency recommended the market withdrawal of several anti-obesity drugs including phentermine, diethylpropion, and mazindol, due to an unfavourable risk to benefit ratio. The first selective CB1 receptor blocker, rimonabant, was available in 56 countries from 2006 but was never approved by the us. food and drug administration (FDA) due to an increased risk of psychiatric adverse events, including depression, anxiety, and suicidal ideation. Subsequently, rimonabant was withdrawn from the European market in 2009.
Definition of Obesity (WHO Criteria) World Health Organization defines obesity as an abnormal or excessive accumulation of body fat that presents a risk to health. In clinical and epidemiological practice, obesity is most assessed using Body Mass Index (BMI), calculated as weight in kilograms divided by the square of height in meters (kg/m²). According to WHO criteria, BMI 18.5–24.9 kg/m² is considered normal, 25.0–29.9 kg/m² as overweight, and ≥30 kg/m² as obesity. Obesity is further subclassified into Class I (30.0–34.9 kg/m²), Class II (35.0–39.9 kg/m²), and Class III (≥40 kg/m²), reflecting increasing health risk. Although BMI does not directly measure body fat percentage, it is strongly correlated with adiposity and is widely used due to its simplicity and reproducibility in large populations (1,4).
Difference Between Overweight and Obesity
Overweight and obesity are distinct categories based on BMI and associated health risks. Overweight (BMI 25.0–29.9 kg/m²) indicates excess body weight relative to height but does not necessarily imply excessive body fat or metabolic dysfunction. Obesity (BMI ≥30 kg/m²), however, represents a pathological excess of adipose tissue associated with increased morbidity and mortality. Research demonstrates that the risk of type 2 diabetes mellitus, hypertension, dyslipidaemia, and cardiovascular disease rises progressively with increasing BMI, particularly beyond 30 kg/m². Additionally, fat distribution—especially central (abdominal) obesity measured by waist circumference—is more strongly associated with metabolic complications than total body weight alone (7,8).
Obesity as a Chronic Metabolic Disease
Obesity is now recognized as a chronic, relapsing, multifactorial metabolic disease rather than merely a lifestyle condition. It results from complex interactions among genetic predisposition, environmental influences, neuroendocrine regulation, and behavioural factors. Excess adipose tissue acts as an active endocrine organ, secreting adipokines and inflammatory mediators that contribute to insulin resistance, chronic low-grade inflammation, and metabolic syndrome. The genetic contribution to obesity is estimated to account for 25–40% of variability in BMI, though polygenic influences predominate in most individuals. Given its chronic and progressive nature, obesity requires long-term management strategies including lifestyle modification, pharmacotherapy, and, in selected cases, bariatric surgery (9,7).
Global Prevalence and Epidemiological Trends
Obesity has reached epidemic proportions globally. According to the World Health Organization, worldwide obesity has nearly tripled since 1975. In 2016, more than 1.9 billion adults were overweight, of whom over 650 million were obese. The prevalence is rising not only in high-income countries but also in low- and middle-income nations, particularly in urban settings. Childhood obesity is also increasing at an alarming rate, predisposing younger populations to early onset of metabolic diseases. Epidemiological studies consistently show a strong association between increasing BMI and higher risks of cardiovascular disease, type 2 diabetes, certain cancers, and all-cause mortality (2,10).
Economic and Social Burden of Obesity
The economic and social burden of obesity is substantial and multifaceted. Direct medical costs include expenses related to the management of diabetes, cardiovascular disease, orthopaedic complications, and obesity-related cancers. Indirect costs arise from reduced productivity, absenteeism, disability, and premature mortality. In many countries, obesity-related healthcare expenditures account for a considerable proportion of total healthcare spending. Beyond economic implications, obesity contributes to social stigma, discrimination, psychological distress, and reduced quality of life. The increasing prevalence of obesity places considerable strain on healthcare systems and underscores the need for comprehensive public health strategies focusing on prevention, early intervention, and long-term management (11,9).
2. Body Mass Index (BMI) Classification (WHO & Asian Criteria)
World Health Organization classifies Body Mass Index (BMI) as a practical anthropometric index to categorize nutritional status in adults. BMI is calculated as weight in kilograms divided by height in meters squared (kg/m²). According to WHO international criteria, BMI 18.5–24.9 kg/m² is considered normal, 25.0–29.9 kg/m² as overweight, and ≥30 kg/m² as obesity. Obesity is further divided into subclasses based on severity. However, because Asian populations develop metabolic complications at lower BMI levels, WHO and expert consultation groups proposed lower cut-off values for Asian populations: normal BMI 18.5–22.9 kg/m², overweight 23.0–24.9 kg/m², and obesity ≥25 kg/m². These modified thresholds improve early identification of cardiometabolic risk in Asian individuals (1,3).
Class I, II and III Obesity (Morbid Obesity)
Obesity is further categorized based on severity to estimate health risk. According to WHO and the National Institutes of Health classification, Class I obesity is defined as BMI 30.0–34.9 kg/m², Class II obesity as BMI 35.0–39.9 kg/m², and Class III obesity as BMI ≥40 kg/m². Class III obesity is often termed “morbid obesity” because it is associated with markedly increased risk of cardiovascular disease, type 2 diabetes mellitus, obstructive sleep apnea, osteoarthritis, and premature mortality. Epidemiological studies demonstrate a progressive rise in morbidity and mortality with increasing BMI categories, particularly beyond 35 kg/m². This classification helps guide clinical decisions regarding pharmacotherapy and bariatric surgery (4,7).
Central vs General Obesity
Obesity may be classified not only by total body fat (general obesity) but also by fat distribution. General obesity refers to overall excess adiposity measured primarily by BMI. In contrast, central obesity (also called abdominal or android obesity) refers to excess fat accumulation in the abdominal region, particularly visceral adipose tissue. Studies have shown that central obesity is more strongly associated with insulin resistance, dyslipidaemia, hypertension, and cardiovascular disease than general obesity. Waist circumference is a simple and reliable measure of central obesity, with cut-off values of >102 cm in men and >88 cm in women indicating increased metabolic risk. Imaging techniques such as computed tomography and magnetic resonance imaging provide accurate assessment of visceral fat but are not practical for routine clinical use. (12,7).
Health Risk Levels Based on BMI and Waist Circumference
Health risk increases progressively with both BMI and waist circumference. Individuals with overweight and obesity have elevated risks of type 2 diabetes, coronary heart disease, stroke, certain cancers, and all-cause mortality. Importantly, individuals with normal BMI but increased waist circumference may still carry high cardiometabolic risk due to excess visceral fat. Clinical guidelines therefore recommend combining BMI with waist circumference to better stratify health risk. For example, a person with BMI 25–29.9 kg/m² and elevated waist circumference has a substantially higher risk than someone with the same BMI but normal waist measurement. This combined assessment improves identification of individuals requiring early intervention and intensive lifestyle modification (8,3).
3. High-Calorie Diet and Processed Foods
Consumption of high-calorie diets rich in saturated fats, refined carbohydrates, and ultra-processed foods is a major contributor to obesity. Energy-dense foods promote positive energy balance when caloric intake exceeds expenditure, leading to triglyceride accumulation in adipose tissue. Diets high in sugar-sweetened beverages and processed snacks are associated with increased visceral fat deposition and insulin resistance. Research indicates that chronic overnutrition alters hypothalamic appetite regulation and promotes adipocyte hypertrophy and hyperplasia. Additionally, excessive intake of refined carbohydrates contributes to hyperinsulinemia, which favours lipogenesis and inhibits lipolysis. Thus, dietary overload is not merely a caloric issue but also a metabolic driver of adiposity and related complications (13,14).
Sedentary Lifestyle and Reduced Physical Activity
Physical inactivity is a critical etiological factor in obesity. Modern lifestyles characterized by prolonged sitting, reduced occupational physical labour, and increased screen time significantly reduce total daily energy expenditure. When energy expenditure declines without a proportional reduction in caloric intake, fat accumulation ensues. Sedentary behaviour also impairs lipid oxidation, decreases insulin sensitivity, and contributes to chronic low-grade inflammation. Studies show that regular physical activity improves glucose utilization, enhances mitochondrial function, and reduces central adiposity. Therefore, insufficient physical activity not only promotes weight gain but also accelerates metabolic dysfunction (13,14).
Genetic and Familial Factors
Genetic predisposition significantly influences susceptibility to obesity. Twin and family studies demonstrate that 25–40% of BMI variability can be attributed to genetic factors. Genes regulate appetite, satiety, energy expenditure, and adipocyte differentiation. Mutations affecting leptin signalling, melanocortin receptors, and neuropeptide pathways may lead to hyperphagia and reduced thermogenesis. Furthermore, familial clustering of obesity reflects both shared genetic makeup and environmental influences such as dietary habits and physical activity patterns. Although genetics alone rarely causes obesity, it increases vulnerability when combined with obesogenic environmental factors (13).
Endocrine Disorders (Hypothyroidism, PCOS, Cushing’s Syndrome)
Certain endocrine disorders contribute to secondary obesity. Hypothyroidism reduces basal metabolic rate, leading to weight gain and fluid retention. Polycystic Ovary Syndrome (PCOS) is associated with insulin resistance, hyperandrogenism, and central obesity, creating a vicious cycle that promotes further metabolic disturbance. Cushing’s syndrome, characterized by chronic glucocorticoid excess, leads to truncal obesity, muscle wasting, and impaired glucose tolerance. Hormonal imbalances in these disorders disrupt normal metabolic regulation and favour fat deposition, particularly in the abdominal region. Early diagnosis and appropriate hormonal therapy are essential to prevent progressive weight gain and metabolic complications (14,13).
Stress, Emotional Eating and Psychological Factors
Psychological stress plays a substantial role in obesity through neuroendocrine and behavioural pathways. Chronic stress activates the hypothalamic–pituitary–adrenal (HPA) axis, increasing cortisol secretion, which promotes visceral fat accumulation and insulin resistance. Emotional eating, characterized by consumption of high-calorie comfort foods in response to stress or negative emotions, further contributes to weight gain. Additionally, depression and anxiety are frequently associated with dysregulated appetite and reduced motivation for physical activity. These psychological factors create a feedback loop that sustains obesity and complicates its management (13).
Sleep Deprivation and Circadian Rhythm Disturbance
Inadequate sleep and disruption of circadian rhythms are increasingly recognized as contributors to obesity. Sleep deprivation alters appetite-regulating hormones, decreasing leptin levels and increasing ghrelin secretion, thereby stimulating hunger and preference for calorie-dense foods. It also impairs glucose metabolism and increases insulin resistance. Chronic circadian misalignment, such as that seen in shift workers, disrupts metabolic homeostasis and promotes adiposity. Epidemiological evidence suggests that individuals sleeping fewer than 6 hours per night have a significantly higher risk of developing obesity compared to those with adequate sleep duration (13).
Environmental and Socioeconomic Influences
Environmental and socioeconomic factors strongly influence obesity prevalence. Urbanization, easy availability of inexpensive processed foods, reduced opportunities for physical activity, and marketing of energy-dense foods contribute to an obesogenic environment. Lower socioeconomic status is associated with limited access to healthy foods, inadequate healthcare, and reduced awareness of lifestyle modification strategies. Cultural practices and social norms also affect dietary patterns and body weight perception. Therefore, obesity is not solely an individual problem, but a complex public health issue shaped by environmental, social, and economic determinants (14).
4. Energy Imbalance Theory
The Energy Imbalance Theory is the fundamental concept underlying the pathogenesis of obesity. It states that obesity develops when energy intake chronically exceeds energy expenditure, resulting in a positive energy balance. Excess calories are stored primarily as triglycerides in adipose tissue. Modern lifestyles characterized by high-calorie diets, processed foods, and reduced physical activity contribute significantly to sustained energy surplus. Although simple in principle, energy balance is tightly regulated by neuroendocrine mechanisms, and even small daily imbalances over time can lead to substantial weight gain. Genetic susceptibility and environmental factors further influence energy storage efficiency and metabolic adaptation, thereby promoting obesity development (15).
Adipose Tissue Expansion and Hypertrophy
Adipose tissue plays a central role in obesity by serving as the primary storage site for excess energy. During positive energy balance, adipose tissue expands through two mechanisms: hypertrophy (increase in adipocyte size) and hyperplasia (increase in adipocyte number). In early obesity, hypertrophy predominates, leading to enlarged adipocytes that become metabolically dysfunctional. Hypertrophic adipocytes exhibit impaired lipid storage capacity, increased lipolysis, and secretion of pro-inflammatory cytokines. As adipose tissue expands beyond its vascular supply, local hypoxia develops, triggering macrophage infiltration and inflammatory signalling pathways. This dysfunctional adipose tissue contributes to metabolic complications associated with obesity (16).
Role of Hypothalamus in Appetite Regulation
The hypothalamus is the primary brain region responsible for regulating appetite and energy homeostasis. Within the hypothalamus, the arcuate nucleus contains two key neuronal populations: orexigenic neurons (NPY/AgRP) that stimulate appetite and anorexigenic neurons (POMC/CART) that suppress food intake. These neurons respond to peripheral hormonal and nutrient signals to maintain energy balance. When regulatory signalling is disrupted, as seen in obesity, hypothalamic inflammation and leptin resistance impair satiety signalling, leading to increased food intake and reduced energy expenditure. Thus, dysfunction of hypothalamic pathways contributes significantly to sustained weight gain (17).
Hormonal Regulation (Leptin, Ghrelin, GLP-1, Insulin)
Hormones play a crucial role in appetite control and metabolic regulation. Leptin, produced by adipocytes, signals satiety to the hypothalamus and reduces food intake; however, in obesity, elevated leptin levels lead to leptin resistance, diminishing its anorexigenic effect. Ghrelin, secreted by the stomach, stimulates hunger and increases before meals, promoting food intake. GLP-1 (glucagon-like peptide-1), released from intestinal L-cells, enhances insulin secretion and promotes satiety, thereby reducing caloric intake. Insulin, beyond its metabolic role in glucose uptake, also acts centrally to suppress appetite. Dysregulation of these hormonal pathways contributes to overeating, weight gain, and metabolic disturbances in obesity (18).
Development of Insulin Resistance
Insulin resistance is a hallmark metabolic complication of obesity. It develops when peripheral tissues such as skeletal muscle, liver, and adipose tissue become less responsive to insulin signalling. Enlarged adipocytes release excessive free fatty acids into circulation, leading to ectopic fat deposition in liver and muscle. Accumulation of intracellular lipid metabolites interferes with insulin receptor signalling pathways. Additionally, pro-inflammatory cytokines such as TNF-α and IL-6 further impair insulin action. As a result, higher insulin levels are required to maintain glucose homeostasis, eventually contributing to hyperinsulinemia and type 2 diabetes mellitus (19).
Chronic Low-Grade Inflammation
Obesity is characterized by chronic low-grade systemic inflammation. Expanded adipose tissue recruits immune cells, particularly macrophages, which shift toward a pro-inflammatory phenotype. These immune cells release inflammatory mediators including TNF-α, IL-6, and C-reactive protein. Persistent inflammatory signalling disrupts insulin signalling pathways and promotes metabolic dysfunction. Unlike acute inflammation, this low-grade inflammation is sustained over prolonged periods and contributes to the development of insulin resistance, cardiovascular disease, and other obesity-related complications. Therefore, obesity is now recognized not only as a metabolic disorder but also as a chronic inflammatory condition (20).
5. Obesity-Related Diseases
Obesity is a chronic, relapsing metabolic disorder characterized by excessive accumulation of adipose tissue that impairs health and predisposes individuals to multiple systemic diseases. It results from a long-term imbalance between energy intake and energy expenditure, influenced by genetic, environmental, hormonal, and behavioural factors. The World Health Organization defines obesity as a body mass index (BMI) ≥30 kg/m², although lower BMI thresholds are recommended for certain Asian populations because of higher cardiometabolic risk at comparatively lower body weights. The global rise in obesity prevalence has made it a major contributor to morbidity, mortality, and healthcare burden worldwide (13).
Cardiovascular disease
Cardiovascular disease is the most significant and life-threatening complication of obesity. Numerous epidemiological studies, including long-term population analyses, have demonstrated a positive association between obesity and coronary artery disease, myocardial infarction, cerebrovascular disease, and congestive heart failure. Although adiposity alone may not directly cause atherosclerosis, obesity contributes indirectly through associated risk factors such as hypertension, diabetes mellitus, dyslipidaemia, and reduced high-density lipoprotein (HDL) cholesterol levels. These metabolic abnormalities accelerate endothelial dysfunction and plaque formation, increasing the risk of thrombotic events and premature cardiovascular mortality (14).
Hypertension
Hypertension is strongly linked with obesity and is one of its most common comorbid conditions. Increased adipose tissue leads to expanded plasma volume, elevated cardiac output, and activation of the renin–angiotensin–aldosterone system, resulting in increased blood pressure. Sodium retention and sympathetic nervous system stimulation further aggravate hypertension in obese individuals. Obesity-related hypertension significantly increases the risk of stroke, heart failure, and kidney disease. Importantly, clinical evidence shows that even moderate weight reduction can produce substantial reductions in blood pressure, emphasizing the importance of lifestyle intervention in management (14).
Type 2 diabetes mellitus
Type 2 diabetes mellitus is a major metabolic consequence of obesity. Excess adipose tissue, particularly visceral fat, releases pro-inflammatory cytokines and adipokines that interfere with insulin signalling pathways. This leads to insulin resistance, reduced glucose uptake by peripheral tissues, and persistent hyperglycaemia. Chronic insulin resistance places increased demand on pancreatic beta cells, eventually resulting in beta-cell dysfunction and overt diabetes. The inflammatory state associated with obesity, often termed “meta inflammation,” further exacerbates glucose intolerance. Therefore, obesity is considered the most important modifiable risk factor for the development of type 2 diabetes mellitus (13).
Dyslipidaemia
Dyslipidaemia frequently accompanies obesity and plays a significant role in cardiovascular complications. Obese individuals commonly exhibit elevated levels of low-density lipoprotein (LDL) cholesterol and triglycerides along with decreased HDL cholesterol. These lipid abnormalities contribute to the formation of atherosclerotic plaques within arterial walls. Altered lipid metabolism in obesity increases hepatic synthesis of very-low-density lipoproteins and impairs lipid clearance, thereby enhancing the risk of coronary heart disease and stroke (14).
Metabolic syndrome
Metabolic syndrome represents a clustering of obesity-related metabolic abnormalities, including central obesity, hyperglycaemia, hypertension, hypertriglyceridemia, and reduced HDL cholesterol. Central adiposity is considered a key pathogenic component because visceral fat is metabolically active and strongly associated with insulin resistance. Individuals with metabolic syndrome have a markedly increased risk of developing cardiovascular disease and type 2 diabetes. The syndrome reflects the interconnected pathophysiological processes of inflammation, hormonal imbalance, and metabolic dysregulation seen in obesity (13).
Gallbladder disease
Gallbladder disease, particularly cholelithiasis, is more prevalent among obese individuals. Obesity alters cholesterol metabolism, leading to supersaturation of bile with cholesterol and promoting gallstone formation. Increased hepatic secretion of cholesterol into bile and reduced gallbladder motility contribute to stone formation. Rapid weight loss, especially following very-low-calorie diets, may further increase the risk of gallstone development (14). Obesity is increasingly recognized as a chronic low-grade inflammatory condition. Adipose tissue acts as an endocrine organ and secretes various pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α), interleukins, and C-reactive protein, while decreasing anti-inflammatory adipokines like adiponectin. Macrophage infiltration into adipose tissue enhances this inflammatory environment. This persistent inflammation contributes to insulin resistance, endothelial dysfunction, atherosclerosis, and progression of metabolic diseases (13). Certain cancers have also been linked to obesity. Chronic hyperinsulinemia, increased levels of insulin-like growth factors, sex hormone alterations, and systemic inflammation create a favourable environment for carcinogenesis. Epidemiological data suggest increased risk of breast, colorectal, endometrial, and other hormone-related cancers in obese individuals. Thus, obesity not only affects metabolic health but also contributes to oncological risk (13). In addition to metabolic and cardiovascular disorders, obesity causes mechanical and functional complications. Excess body weight places increased stress on weight-bearing joints, leading to osteoarthritis and chronic musculoskeletal pain. Accumulation of adipose tissue in the thoracic and abdominal regions impairs respiratory mechanics, predisposing individuals to reduced pulmonary function and sleep-disordered breathing. These complications significantly reduce quality of life and functional capacity.14 Diagnosis and Clinical Evaluation of Obesity (1).
6. Body Mass Index (BMI)
Calculation and Clinical Use Body Mass Index (BMI) is the most widely used and practical method for diagnosing obesity in clinical and epidemiological settings. It is calculated using the formula: BMI = Weight (kg) / Height (m²). According to international guidelines, BMI values are classified as follows: normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), and obesity (≥30 kg/m²). Obesity is further subclassified into Grade I (30–34.9 kg/m²), Grade II (35–39.9 kg/m²), and Grade III (≥40 kg/m²). Although BMI correlates well with body fat at the population level, it does not differentiate between fat mass and lean body mass. Therefore, muscular individuals may be misclassified as overweight or obese. Despite this limitation, BMI remains the primary screening tool due to its simplicity, reproducibility, and strong association with morbidity and mortality risk (7).
Waist Circumference and Waist–Hip Ratio
Assessment of fat distribution is a vital component of clinical evaluation because central (abdominal) obesity is more strongly associated with metabolic and cardiovascular complications than overall obesity. Waist circumference (WC) is measured midway between the lower rib margin and the iliac crest. Abnormal values are ≥102 cm in men and ≥88 cm in women. Waist–hip ratio (WHR) is calculated by dividing waist circumference by hip circumference. Elevated WC and WHR indicate visceral fat accumulation, which is linked to insulin resistance, type 2 diabetes mellitus, dyslipidaemia, and cardiovascular disease. Studies suggest that waist circumference is a better predictor of metabolic risk than BMI alone. Hence, combining BMI with waist measurements improves clinical risk stratification.
Body Fat Percentage Assessment Body fat percentage
provides a more accurate representation of adiposity than BMI because it distinguishes fat mass from lean mass. Obesity is defined as body fat ≥25% in men and ≥35% in women. Methods for assessment include skinfold thickness measurement, bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DEXA), underwater weighing, and fat mass index (FMI). Among these, BIA is commonly used in clinical practice due to its convenience and non-invasive nature. However, it requires population-specific predictive equations for accuracy. Studies have shown that BMI may misclassify individuals when compared with percentage body fat and FMI, highlighting the importance of body composition analysis in selected patients (21).
Laboratory Investigations
Laboratory evaluation is essential to detect obesity-related metabolic complications. The standard investigations include fasting blood glucose, HbA1c, lipid profile (total cholesterol, LDL, HDL, triglycerides), and sometimes liver function tests. Elevated fasting glucose and HbA1c indicate impaired glucose tolerance or type 2 diabetes mellitus. Dyslipidaemia in obesity typically presents as elevated triglycerides, increased LDL cholesterol, and reduced HDL cholesterol. These metabolic abnormalities significantly increase cardiovascular risk. Therefore, laboratory screening is crucial not only for diagnosis but also for risk assessment and therapeutic monitoring in obese patients (22).
Metabolic Syndrome
Criteria Metabolic syndrome is a cluster of metabolic abnormalities commonly associated with obesity, particularly central obesity. Diagnostic criteria include abdominal obesity, elevated triglycerides (≥150 mg/dL), reduced HDL cholesterol (<40 mg/dL in men, <50 mg/dL in women), elevated blood pressure (≥130/85 mmHg), and fasting glucose ≥100 mg/dL. The presence of three or more of these criteria confirms the diagnosis. Central adiposity plays a key role in the pathogenesis of insulin resistance, systemic inflammation, and atherogenesis. Identification of metabolic syndrome is important because it significantly increases the risk of cardiovascular disease and type 2 diabetes (7).
Table: Clinical Evaluation Parameters in Obesity
|
Parameter |
Method of Assessment |
Diagnostic Criteria |
Clinical Significance |
|
BMI |
Weight (kg) / Height (m²) |
≥30 kg/m² = Obesity |
General obesity classification |
|
Waist Circumference |
Measuring tape |
≥102 cm (men), ≥88 cm (women) |
Central obesity, metabolic risk |
|
Waist–Hip Ratio |
WC / HC |
>0.90 (men), >0.85 (women) |
Visceral fat risk |
|
Body Fat % |
BIA, DEXA, skinfold |
≥25% (men), ≥35% (women) |
Accurate adiposity measure |
|
Fasting Glucose |
Blood test |
≥100 mg/dL |
Diabetes risk |
|
HbA1c |
Blood test |
≥6.5% (diabetes) |
Long-term glycemic control |
|
Lipid Profile |
Blood test |
TG ≥150 mg/dL, Low HDL |
Cardiovascular risk |
|
Blood Pressure |
Sphygmomanometer |
≥130/85 mmHg |
Hypertension risk |
7. Non-Pharmacological Management of Obesity
Medical Nutrition Therapy (Calorie Restriction and Balanced Diet) Medical nutrition therapy (MNT)
MNT is the cornerstone of obesity management and is based on the principle of creating a sustained negative energy balance. A daily caloric deficit of 500–1000 kcal is recommended to achieve gradual weight loss of 0.5–1 kg per week. Balanced diets typically include 45–65% carbohydrates, 20–35% fats, and 10–20% proteins, with emphasis on fibre-rich foods, fruits, vegetables, whole grains, and lean protein sources. Clinical evidence demonstrates that structured dietary counselling significantly improves weight reduction and reduces obesity-related comorbidities such as hypertension, dyslipidaemia, and type 2 diabetes. Importantly, dietary intervention must be individualized according to age, sex, cultural preference, metabolic risk, and comorbid conditions to ensure long-term adherence and effectiveness (22).
Low-Carbohydrate and Ketogenic Diet
Low-carbohydrate diets restrict carbohydrate intake to less than 130 g/day, while ketogenic diets further reduce intake to less than 50 g/day, inducing a metabolic state of ketosis. In ketosis, the body shifts from glucose metabolism to fat oxidation, producing ketone bodies for energy. Studies show that these diets promote rapid short-term weight loss, improved insulin sensitivity, and reduced triglyceride levels. The mechanisms include appetite suppression, increased satiety from protein intake, and enhanced fat metabolism. However, long-term sustainability remains a concern, and potential risks such as micronutrient deficiency and lipid abnormalities require monitoring. Therefore, these diets should be medically supervised, especially in patients with metabolic syndrome or diabetes (23).
Mediterranean Diet
The Mediterranean diet emphasizes high consumption of fruits, vegetables, legumes, nuts, olive oil, and whole grains, moderate intake of fish and poultry, and low intake of red meat and processed foods. This dietary pattern is rich in monounsaturated fats and antioxidants, which contribute to cardiometabolic protection. Evidence indicates that the Mediterranean diet improves lipid profile, reduces inflammatory markers, enhances insulin sensitivity, and lowers cardiovascular risk in obese individuals. Unlike restrictive diets, it promotes sustainable eating habits and is associated with long-term weight maintenance (7).
Intermittent Fasting Intermittent fasting (IF):
IF involves structured periods of fasting and eating, such as the 16:8 method or alternate-day fasting. IF promotes weight loss primarily through caloric restriction and metabolic switching from glucose to fat utilization. It has been shown to improve insulin sensitivity, reduce visceral fat accumulation, and decrease systemic inflammation. Some studies suggest that intermittent fasting may enhance metabolic flexibility and mitochondrial function. However, adherence varies among individuals, and IF may not be suitable for pregnant women, elderly individuals, or patients with eating disorders. Therefore, patient selection and counselling are essential (23).
Physical Activity (Aerobic and Resistance Training)
Physical activity plays a critical role in both weight reduction and long-term weight maintenance. Aerobic exercises such as brisk walking, cycling, or swimming increase energy expenditure and improve cardiovascular fitness. Resistance training enhances lean body mass, increases resting metabolic rate, and prevents sarcopenia during weight loss. Current recommendations suggest at least 150–300 minutes of moderate-intensity aerobic activity per week, combined with resistance training two to three times weekly. Exercise also improves insulin sensitivity, reduces blood pr
Alauddin Basha I.*, Ashwin S., Dhinakaran E., Loganantham B., Manibharathi M., Srikanth N., Obesity & Innovative Anti-Obesity Drugs, Int. J. Sci. R. Tech., 2026, 3 (4), 57-80. https://doi.org/10.5281/zenodo.19389110
10.5281/zenodo.19389110
