ESI Clinical Practice Guidelines for the Evaluation and Management of Obesity in India – An Update (2025)

INTRODUCTION The previous endocrine society of India clinical practice recommendations were published in 2022, however a lot of developments have occurred in the obesity space in the Indian setting following that.[1,2] From more recent clinical studies in the Indian population to newer approvals, availability and reduced cost for some of the anti-obesity medications, led to the need to develop this document. While the previous document was exhaustive, the four key domains that were identified as key areas, where an update is required included the fast-changing epidemiology of obesity, a summary of the pharmacological options, the associated medication counselling, and the novel concepts in the psycho-social aspects of obesity management. SECTION A – FAST CHANGING EPIDEMIOLOGY OF INDIAN OBESITY Obesity has reached pandemic proportions globally, and the prevalence is rapidly increasing even in developing countries like India. Obesity is defined as presence of excessive fat in the body that leads to an increased risk of adverse health outcome. This excessive fat could be present either globally, in specific regions of the body or in organs as ectopic lipids.[3] Globally, approximately 650 million adult people and about 340 million children and adolescence between the age of 5 to 19 years, live with obesity and these numbers are rapidly increasing.[4] As per the most recent data published from the United States, using the National Health and Nutrition Examination Survey about 42.4% of adults have a body mass index of more than equal to 30 kg/m2 and 20.9% of children have a ≥95th age and gender matched BMI percentile.[5] The World Obesity Federation now provides a national obesity risk for each country. This represents a composite score based on the obesity prevalence, rate of increase and indicators of treatment. India has been given a score of 7 out of 10. In the recently published, The Indian Council of Medical Research–India Diabetes (ICMR-INDIAB) study, which is a nationwide cross-sectional population-based survey among individuals above the age of aged 20 years from urban and rural areas across 31 states and Union territories of the country.[6] Generalized and abdominal obesity was defined as per the WHO Asia Pacific guidelines. A whopping number of estimated 254 million people with generalized obesity (28.6%) and 351 million individuals with abdominal obesity (39.5%) were found in this study. The state with the highest rates of abdominal and generalized obesity was Puducherry (53.3% and 61.2%) and that with the lowest rates was Jharkhand (11.6% and 18.4%). Furthermore, the urban population in these states was found to have a prevalence of more than 25%.[3] Obesity data from India across the life span Obesity in Indian children Child hood obesity has shown a rising trend over the last few decades. Initial studies in India done from Delhi,[7-10] Chandigarh,[11] Chennai,[12] Pune,[13] and West Bengal,[14] have shown the prevalence of childhood obesity around 10%–12% and overweight around 12%–22%. More recent literature, however has shown a significantly higher prevalence of obesity approaching in up to 30% of patients.[15-17] Obesity in young adults among the Indian population In another study, conducted among 647,168 women with a median age of about 30 years the prevalence of overweight women was 22.6% and that of women with obesity was 10.7%. Older women, those who were married, had previous history of pregnancy, were highly educated, wealthy, and living in urban regions had higher prevalence and odds of having overweight/obesity.[18] This has been further corroborated from the data obtained through the national family health surveys that have shown a prevalence of overweight and obesity between 35% to 40%.[19] Obesity in the older population in India In a recent study by Singhania et al.,[20] the prevalence of overweight and obesity in rural middle aged postmenopausal women in North India was found to be about 35.5%. In another study among rural south Indian women, predominantly farmers with a mean age of about 60 years, about two thirds of the study population was found to have body mass index (BMI) in obese range.[21] A recent paper by Verma et al.[22] analysing the prevalence of obesity through the Longitudinal Ageing Study in India found the prevalence to be 27% in 72,250 older adults. Prevalence of the unique South Asian thin-fat obesity The South Asian ethnicity is known to have a predisposition to develop obesity related complications at a lower body mass index.[23,24] This was first shown in the famous paper called the YY Paradox and has thus been validated in several studies by different names like the normal weight obesity, metabolic obesity, skinny fat and thin-fat phenotype.[25] The prevalence of this phenotype has been about 15% in Chennai and about 16% in Mumbai.[26,27] In another recent study by Kapoor et al.[28] from Kerala the prevalence of normal weight obesity among the high diabetes risk individuals was found to be about 30 percent of the population. They were also found to have a significantly higher prevalence of diabetes, hypertension and dyslipidaemia as compared to non-obese, normal fat containing individuals and were resistant to change following a life style intervention.[28,29] Concordance with the Lancet Commission on obesity The ESI guidelines are concordant with the philosophy expressed by the Lancet Commission on obesity.[30] In fact, in many ways, the ESI’s statements ante-date, and amplify, the message shared by the Commission. The multifactorial etiopathogenesis of obesity, and the varied clinical presentations of the disease, are clearly mentioned by ESI. The need for complete barophenotypic characterization has been highlighted in the ESI recommendations. This includes the need for multiple anthropometric measurements, and addresses the syndromes of normal weight obesity, as well as sarcopenic obesity. The disparate diagnostic criteria for clinical obesity listed in the Lancet publication have been grouped in a reader friendly 4M format (medical, musculoskeletal, mood related and monetary) in our recommendations. The ESI statement lays equal emphasis on the psychosocial as well as biomedical determinants and downstream effects of obesity. Thus, they offer a balanced perspective of the syndrome. The threshold of diagnosis of clinical obesity, or the threshold of intervention, is not based on BMI alone. This message is evidence in the ESI document as well, which calls for a comprehensive evaluation of the patient. The various interventions available, and practical means of behavioural therapy, are detailed in the ESI recommendation, too. The ESI guidelines represent a person-centred approach to obesity management. This is evident in our continued use of the word ‘overweight’, which we feel is less stigmatizing, less threatening, and more person friendly than obesity. At the same time, the guidelines offer definitive advice regarding thresholds of intervention, whether by non-pharmacological, pharmacological, or surgical means. With regular updates and addenda, read in conjunction with global advances in obesity science, the ESI guidelines will continue to serve as the bellwether upon which Indian obesity care will function. SECTION B – NEXT GENERATION MEDICINES FOR OBESITY MANAGEMENT Liraglutide Glucagon-like peptide 1 (GLP1) receptor agonist liraglutide has 97 percent sequence homology to human GLP-1 [Table 1]. The half-life of liraglutide is 11 to 13 hour due to its avid binding to serum albumin.[31,32] LEADER trials are the phase 3 clinical trials of liraglutide on glycaemic efficiency of the drug in patients with type-2 diabetes mellitus. With the use of doses of 1.2 mg and 1.8 mg subcutaneous liraglutide daily, the Hba1c reduction have been 1.1%–1.8% and the weight loss documented have been 2–3 kg across the LEADER trials.[33] However, Liraglutide reduces body weight in a dose dependent manner. People with obesity without diabetes lost a mean weight of 6.2–8 kgs (7.4% body weight) with 3 mg of daily injectable liraglutide in Satiety and Clinical Adiposity—Liraglutide Evidence clinical trial (SCALE) trials.[34,35] Liraglutide 3 mg has also been investigated in patients with diabetes and obesity (SCALE Diabetes and SCALE insulin).[34,35] When liraglutide 3 mg was tried in people with diabetes and obesity with three oral antidiabetic medication the weight reduction observed was 6% with liraglutide vs 2% kg with placebo and when liraglutide 3 mg was used in population with obesity and diabetes on insulin the weight loss was 5.8% vs 1.2% in placebo arm.Table 1: Currently approved medications for obesity managementSemaglutide Semaglutide is currently one of the potent and efficacious GLP-1RA approved for weight loss and diabetes. Semaglutide is approved in once daily oral formulations (3, 7 and 14 mg) and once weekly (OW) SC (0.5, 1.0 and 2.0 mg) dosage for the management of type-2 diabetes mellitus and injectable semaglutide 2.4 mg OW for management of weight loss.[31-33] However, only the oral formulation is available in India for management of type-2 diabetes and Injectable semaglutide 2.4 mg has been approved by drug controller general of India for obesity management [Table 2]. However, injectable form is likely to be available in the next 24 months in a generic form.Table 2: Upcoming drugs for obesity managementInjectable semaglutide Semaglutide Treatment Effect in People with Obesity (STEP) trials are the phase 3 clinical trial program with semaglutide 2.4 mg OW for the management of obesity. Semaglutide 2.4 mg showed weight loss of up to 17.4% at the end of trial and one third of patients lost >20% of their baseline body weight.[36-43]Table 3 summarized different STEP trials. Participants who received semaglutide 2.4 mg over 104 weeks achieved a mean weight loss of 15.2% demonstrating a persistent effect of weight loss and other weight-related endpoints over a 2-year period. STEP 1 extension trial showed discontinuation of therapy for 1 year will lead to regain of two third of lost body weight. STEP trials also showed improvement in cardiometabolic risk factors like reduction in blood pressures, lipids and Hs C-Reactive Protein (CRP) levels.[37-43] More than 80% of subjects reversed to normoglycemia from prediabetes in STEP trials. Inj semaglutide has been approved for the management of obesity in children of 12 years of age and above based on STEP TEEN trial.[44] SELECT, a cardiovascular outcomes trial with semaglutide 2.4 mg has shown significant reduction (20%) in 3 point major adverse cardiovascular events in patients with overweight or obesity along with CVD.[45] Semaglutide also showed functional improvement in heart failure with preserved ejection fraction (HFpEF) in obese patients in STEP HFpEF trials. STEP trials have also showed the safety profile of semaglutide is in line with other GLP-1RAs as a class. Most common side effects are GI adverse events which are transient and mild to moderate in nature.[37-43]Table 3: STEP: Phase 3 clinical trial programme for Inj Semaglutide 2.4 mg[ 6-13 ]Oral semaglutide Oral semaglutide of 14 mg has been comparable to 1 mg injectable semaglutide in terms of weight reducing potential. PIONEER PLUS trial has taken higher strengths of oral semaglutide (25 mg and 50 mg) in people with obesity and type-2 diabetes mellitus.[46] In this trial oral semaglutide 50 mg showed a significantly higher weight loss vs. oral semaglutide 14 mg (−9.2 vs. −4.5 Kg, P < 0.0001) at the end of 68 weeks. However, OASIS 1 trial has taken 50 mg oral semaglutide against placebo in people living with obesity without T2DM showing a placebo-subtracted weight loss of −15.6% at week 68.[46] Cagri-Sema Cagri-Sema, a combination of Semaglutide and Cagrilintide is expected to further revolutionize the obesity management. Cagrilintide, is a novel long-acting amylin analogue peptide. In the hypothalamus and hindbrain, cagrilintide and semaglutide both target neurons that are relevant for homeostatic and hedonic food intake via different receptors.[47] Both will lead to weight loss via reduced appetite and cravings, improved control of eating and reduced calorie intake.[48] Cagrilintide has a half-life of 180 h thus can be used in combination with semaglutide as a once weekly injection for synergistic weight loss benefits. CagriSema has potential to provide additional weight loss without compromising tolerability. CagriSema appears to have a safe and well-tolerated profile in people with overweight and obesity.[49] In a phase 2 study Cagrilintide 4.5 mg OW alone showed weight loss up to 10.8% after 26 weeks. Weight loss increased with increasing dose of cagrilintide with significantly greater weight loss after 26 weeks at all dose levels vs. placebo, and for 4.5 mg vs. liraglutide 3.0 mg. GI adverse event and treatment discontinuation rate were lower with cagrilintide in comparison to liraglutide 3.0 mg.[49] In a phase 1 study by Enebo et al.,[50] compared semaglutide 2.4 mg alone to the same dose of semaglutide combined with increasing doses of cagrilintide [Table 4]. Remarkably, over a period of 20 weeks, the combination therapy achieved a weight loss of up to 17.1%. This level of weight reduction exceeds what has been previously observed with any other weight loss treatment, highlighting the potential effectiveness of this combined approach.Table 4: Phase 1 study of Cagri-SemaCurrently, Cagrisema is undergoing a robust phase 3 clinical trial program with the name of REDIFINE to evaluate efficacy and safety of Cagri-Sema in obesity. The recently announced topline results from REDIFINE 1 trial [Table 5] showed weight loss of 22.7% with cagrisema after 68 weeks compared to a reduction of 11.8% with cagrilintide 2.4 mg, 16.1% with semaglutide 2.4 mg and 2.3% with placebo in participants with overweight or obesity, while achieving a well-tolerated safety profile.[51]Table 5: REDIFINE Phase 3 program for Cagri-Sema[ 24-30 ]Tirzepatide Tirzepatide is an imbalanced dual agonist with glucose-dependent insulinotropic polypeptide (GIP) activity similar to the native molecule and GLP-1 activity five times lower.[52] It has a half-life of 5 days due to a C20-fatty acid chain attached to the 39 amino acid peptide chain.[53] It enhances insulin secretion: in the first and second phases and reduces the plasma glucagon levels resulting in glycaemic control.[54] It also causes weight loss by delaying gastric emptying and suppressing the appetite.[55] The initial clinical trials for Tirzepatide were done in people with type 2 diabetes and were named the SURPASS trials, which showed significant weight reduction in these participants. This led to the development of the SURMOUNT trials that was designed specifically to look at the obesity outcomes. SURMOUNT 1 was a Phase 3 trial which studied the efficacy and safety of tirzepatide in patients with obesity. At 72 weeks, the mean percentage change in body weight was −15.0% with 5 mg weekly dose, −19.5% with 10 mg dose, and −20.9% with 15 mg dose. SURMOUNT 2 was the next phase 3 trial that followed SUMOUNT 1 but was conducted in people with type 2 diabetes mellitus. Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg was –12·8% and with 15 mg was –14·7%.[56] SURMOUNT 3 was performed to study the effects of tirzepatide on weight reduction after 12 weeks of Successful (≥5% weight reduction) intensive lifestyle intervention. The results showed that the coprimary endpoint of additional mean per cent weight change from randomization to week 72`Q was met with changes of −18.4% (0.7) with tirzepatide and 2.5% (1.0) with placebo treatment percentage The coprimary endpoint of the percentage of participants achieving additional weight reduction was met with with tirzepatide and with placebo achieving this In SURMOUNT the continued Treatment with Tirzepatide for of Weight in with Participants who the period a mean weight reduction of The mean percent weight change from week to week was with tirzepatide vs with It is available in the Indian and is approved for weight loss in India. It as a of mg and 5 mg and is to be in the between and is at a lower dose of mg per week which is increased to 5 mg after weeks. It is further increased with mg per to a dose not 15 mg. subcutaneous the to plasma of tirzepatide from to 72 The mean of tirzepatide following subcutaneous was plasma tirzepatide were achieved following weeks of dose is required for or data on end and is The is in the or once a without any to the It be given as or The of be In of a dose, the is less than the dose as as with the next dose at its the is more than the dose and the next dose at the The of weekly can be as as is more than between the two be in patients with BMI kg/m2 or in individuals with a BMI kg/m2 with at one associated as type 2 diabetes and Tirzepatide be where a weight loss target of is Both tirzepatide and injectable semaglutide be where a weight loss target of only is SECTION – FOR is an of anti-obesity medication is required not only to but therapy as The and of medication to the type and dose of drug However, the of the use the format to a for anti-obesity medication This can be used by and to the person living with obesity, and their to the use of This will from person to and to The and of the with the care the need for as the of due to obesity. The potential and of of be shared in a manner. The of weight as well as cardiovascular and can be using relevant and medications are one of the management for obesity. use not the need for and regular at and complications of obesity are also along with A is also while or therapy for obesity. The expected of weight can be from the results of trials. This can be shared with individuals obesity treatment. 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This be read and in clinical practice with the previous and not to provide a comprehensive management for management of obesity in people living India. This the recent newer medications and the advice that be given when these these guidelines provide the most on obesity is to that same management for all people living with obesity. The treatment be and based on of person to the and of are of of was not used in or of the