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 ≥95^th 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,[7,8,9,10] 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.[15,16,17]

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 management

Medications	Class/MOA	Dose	%weight loss from baseline[7,8,30]	Adverse effects	Contraindications/warnings
Orlistat	Lipase inhibitor	120 mg PO thrice daily before food	4.6 to 10.2% v/s 1.6 to 6.6% with placebo [Studies ranging from 1 to 2 years]	-Steatorrhea - Fecal incontinence - Abdominal pain - Oily spotting - Fat soluble vitamin deficiency	Warnings:  -Oxalate nephrolithiasis  - Cholelithiasis  - Hepatic failure (rare) -Decreased absorption of cyclosporine, thyroid hormones, antiepileptic drugs Contraindications: -Pregnancy  - Hypersensitivity to drug  - Malabsorption syndromes  - Cholestasis -Pregnancy and breastfeeding
Liraglutide (3 mg)	GLP 1 receptor agonist	Start with 0.6 mg SC QD and uptitrate by 0.6 mg weekly till a dose of 3 mg is reached while monitoring for side effects.	6.0 to 8.0% v/s 0.2 to 2.6% with placebo [Studies of 56 weeks duration]	-Nausea - Vomiting -Dyspepsia - Bloating - Abdominal distension -Diarrhea - Constipation -Increased heart rate - Hypoglycaemia - Headache - Dizziness - Fatigue	Warnings:  -injection site reactions  - pancreatitis  - acute cholelithiasis and cholecystitis -tachycardia  - acute kidney Injury -chronic kidney disease  - suicidal behaviour and ideation Contraindications: -Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia 2  - Pregnancy and breastfeeding
Phentermine/topiramate	Phentermine- Norepinephrine releasing drug Topiramate - GABA receptor modulation	Starting dose: 3.75/23 mg PO QD for 2 weeks. From day 15 increase to 7.5/46 mg PO QD, continue for 12 weeks. After 12 weeks if patient has not lost at least 3% of baseline body weight, increase to 11.25/69 mg for 14 days, followed by an increase to 15/92 mg (maximum dose). After 12 weeks on maximum dose if weight loss is <5% of baseline, then the drug can be stopped.	7.8 to 9.3% (7.5/46 mg dose) 10.5 to 12.1% (11.25/69 mg dose) 2.5% to 7.8 (placebo) [Studies of 108 weeks duration]	-Headache - Paraesthesia -Dizziness - Insomnia - Xerostomia - Dysgeusia -Depression - Anxiety - Cognitive impairment CV safety not established	Warnings:  -Metabolic acidosis  - Cognitive impairment -Elevated heart rate  - Nephrolithiasis -Hypokalaemia  - Mood disorders Contraindications: -Glaucoma -Hyperthyroidism  - Monoamine oxidase inhibitor (MAOI) administration  - Pregnancy and breastfeeding
Semaglutide 2.4 mg (injectable)	GLP 1 receptor agonist	Titrate every 4 weeks. Start with 0.25 mg SC QW, then subsequently increase to 0.5 mg, 1 mg, 1.7 mg and finally 2.4 mg SC QW as tolerated by the patient.	16.9% v/s 2.4 (placebo) [over 1 year]	-Nausea - Vomiting - Abdominal distension - Constipation - Diarrhea - Headache - Gastroesophageal reflux disease - Dizziness	Warnings:  -injection site reactions -pancreatitis  - acute cholelithiasis and cholecystitis -tachycardia -acute kidney Injury -chronic kidney disease  - suicidal behaviour and ideation Contraindications: -Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia 2 -Pregnancy and breastfeeding
Naltrexone/Bupropion	naltrexone -mu-opioid receptor antagonist Bupropion - dopamine and norepinephrine reuptake inhibitor	1 tablet: 8/90 mg (8 mg naltrexone/90 mg bupropion) Week 1: 1 tablet PO QAM Week 2: 1 tab PO QAM and 1 tab PO QHS Week 3: 2 tab PO QAM and 1 tab PO QHS Week 4: 2 tab PO QAM and 2 tab PO QHS Maximum dose: 32 mg naltrexone, 360 mg bupropion (2 tablets BID)	5.0 to 6.4% versus 1.2 to 1.8% (placebo) [Studies of 56 weeks duration]	-Nausea - Vomiting - Constipation - Diarrhea - Dry mouth - Dizziness -Anxiety -Insomnia	Warnings:  -Suicidal behaviour and ideation  - Neuropsychiatric symptoms -Seizures  - Increased BP and heart rate -Hepatotoxicity Contraindications: -Uncontrolled hypertension -Seizure disorder  - Eating disorders due to seizure risk -Chronic use of opioid drugs  - Abrupt discontinuation of alcohol  - MAOI use  - Pregnancy and breastfeeding
Tirzepatide	Glucose- dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist	Titrate every 4 weeks. Start with 2.5 mg SC QW, then subsequently increase to 5 mg, 7.5 mg, 10 mg, 12.5 mg and finally 15 mg SC QW as tolerated by the patient.	15.0% with 5 mg weekly dose, −19.5% with 10 mg dose, and −20.9% with 15 mg dose	-Nausea -Vomiting - Abdominal distension - Constipation - Diarrhea - Headache -Gastroesophageal reflux disease -Dizziness	Warnings:  -injection site reactions -pancreatitis  - acute cholelithiasis and cholecystitis -tachycardia -acute kidney Injury -chronic kidney disease  - suicidal behaviour and ideation Contraindications: -Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia 2 -Pregnancy and breastfeeding

MOA=Mechanism of action, PO=Per oral

Semaglutide

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.[31,32,33] 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 management

Drug	Mechanism of action	Clinical trial	Results
High dose Oral semaglutide	Glucagon-like peptide-1 receptor agonist	OASIS 1 (Phase 3)	At end of week 68, Mean percentage change in weight was −15.0% with 50-mg dose
Retatrutide	Glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptor agonist	Jastreboff et al.[71] (Phase 2) Dose–response relationships of Retatrutide with respect to side effects, safety, and efficacy for the treatment of obesity	Least squares mean percentage change in body weight was as high as −17.9 at the end of 24 weeks and −24.2 at the end of 48 weeks
CagriSema (cagrilintide 2·4 mg + semaglutide 2.4 mg)	Amylin analogue and glucagon-like peptide-1 receptor agonist	Frias et al.[72] (Phase 2) Efficacy and safety of co-administered semaglutide with cagrilintide (CagriSema) in participants with type 2 diabetes.	At week 32, the estimated mean change from baseline was -15.6%
Survodutide	Glucagon receptor–glucagon-like peptide-1 receptor dual agonist	le Roux et al.[73] (Phase 2) safety, tolerability, and efficacy of survodutide in obesity management.	At week 46, mean changes in bodyweight from baseline were −6.2% with 0.6 mg; −12.5% with 2.4 mg; −13.2% with 3.6 mg and −14.9% with 4.8 mg dose
		Blüher et al.[74] (Phase 2) Dose–response effects on HbA1c and bodyweight reduction of survodutide compared with placebo and openlabel semaglutide in people with type 2 diabetes	After 16 weeks of treatment, the relative decrease in bodyweight from baseline (key secondary endpoint) for various dose groups of Survotdutide was greater than for placebo (P<0.001), with a maximum adjusted mean MMRM estimate for relative bodyweight reduction of −8.7%. Survodutide doses of ≥1.8 mg qw produced greater adjusted mean (95% CI) bodyweight reductions than semaglutide up to 1.0 mg qw (DG3 [n=36] vs semaglutide [n=45]: −6.6% [−7.9, −5.3] vs –5.3% [−6.6, −4.1])
Orforglipron	Nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist	Wharton et al.[75] (Phase 2) Efficacy and safety of orforglipron as a once-daily oral therapy for weight reduction in adults with obesity.	at week 36, the estimated mean change from baseline in body weight was −9.4% with the 12-mg, −12.5% with 24-mg, −13.5% with 36-mg and −14.7% with 45- mg dose
		Frias et al.[76] (Phase 2) Efficacy and safety of orforglipron versus placebo or dulaglutide in participants with type 2 diabetes.	Change in mean bodyweight at week 26 was up to –10.1 kg with orforglipron versus –2.2 kg (–3.6 to –0.7) for placebo and –3.9 kg (–5.3 to –2.4) for dulaglutide
Ecnoglutide	Long-acting glucagon-like peptide-1 analogy	Zhu et al.[77] (Phase 2) Efficacy, tolerability, and safety of Ecnoglutide in adults with obesity.	Least square mean body weight reduction at the end of 26 weeks was -11.5% with 1.2 mg, 11.2% with 1.8 mg and -14.7% with 2.4 mg dose.

Injectable 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.[36,37,38,39,40,41,42,43] 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.[37,38,39,40,41,42,43] 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.[37,38,39,40,41,42,43]

Table 3.

STEP: Phase 3 clinical trial programme for Inj Semaglutide 2.4 mg[6,7,8,9,10,11,12,13]

STEP	Remarks	Change in body wt. (%)^	Change in body wt. (%)^^	≥15% weight loss (% participants)	≥20% weight loss (% participant)
1	Weight management	14.9	16.9	50.5	32
2**	Weight management in T2DM	9.6	10.6	25.8	13.1
3	Weight management with IBT	16	17.6	55.8	35.7
4	Sustained weight management	17.4	18.2	63.7	39.6
5	Long term weight management	15.2	16.7	52.1	36.1
6	Weight management in East Asians (includes T2D)	13.2	13.5	40.9	19.7
7*	Weight management in Asians (includes T2D)	12.1	12.8	34.5	14.3
8	H2H vs Liraglutide	15.8	17.1	55.6	38.5
9	in People with Obesity and knee osteoarthritis. Change in WOMAC pain score by 41.7 points	13.7	12.1	45.6	22.3
10	Reversion to normoglycaemia in participants with obesity and prediabetes. 81% subjects with prediabetes at the end of 1 year reverse to normoglycemia	13.9	-	48.1	24.8
11	Obesity in Korea and Thailand	Ongoing
STEP UP	With dose 7.2 mg	Ongoing

*After 44 weeks **in T2DM, ^Treatment policy estimand, ^^Trial product estimand. STEP=Semaglutide treatment effect in people with obesity, IBT=Intensive behavioral therapy

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-Sema

	Mean estimate	Treatment difference vs placebo, sema 2.4 mg	95% CI
Cagri 0.16 mg, Sema 2.4 mg	−8.3	1.4	[−2.6; 5.4]
Cagri 0.3 mg, Sema 2.4 mg	−10.0	−0.3	[−4.1; 3.6]
Cagri 0.6 mg, Sema 2.4 mg	−10.6	−0.9	[−5.0; 3.3]
Cagri 1.2 mg, Sema 2.4 mg	−15.7	−6.0	[−9.9; −2.0]
Cagri 2.4 mg, Sema 2.4 mg	−17.1	−7.4	[−11.2; −3.5]
Cagri 4.5 mg, Sema 2.4 mg	−15.4	−7.4	[−12.8; −2.1]
Placebo, Sema 2.4 mg	−9.8
Placebo, Sema 2.4 mg (comparator for cagri 4.5 mg, sema 2.4 mg arm)	−8.0

Currently, 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[24,25,26,27,28,29,30]

Redifine	Remarks	n
1	Weight management	3400
2	Weight management in T2D	1200
3	CVOT	7000
4	H2H vs Tirzeptitide	800
5	Weight management in east Asian patient population	330
6	Weight management in China	300

CVOT=Cardiovascular outcomes trial

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 (estimated treatment difference −20.8 percentage points. The coprimary endpoint of the percentage of participants achieving additional weight reduction ≥5% was met with 87.5% (2.2) with tirzepatide and 16.5% (3.0) with placebo achieving this threshold. In SURMOUNT 4 (Phase 3) Studied the continued Treatment with Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity. Participants who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was −5.5% with tirzepatide vs +14.0% with placebo.[56]

It is available in the Indian market and is approved for weight loss in India. It comes as a vial of 2.5 mg and 5 mg and is recommended to be stored in the refrigerator between 2°C and 8°C. Initially, it is started at a lower dose of 2.5 mg subcutaneously per week which is increased to 5 mg after 4 weeks. It is further increased with 2.5 mg increment per month to a maximal tolerated dose not exceeding 15 mg. Following subcutaneous administration, the time to maximum plasma concentration of tirzepatide ranges from 8 to 72 hour. The mean absolute bioavailability of tirzepatide following subcutaneous administration was 80%. Steady-state plasma tirzepatide concentrations were achieved following 4 weeks of once-weekly administration. No dose adjustment is required for hepatic or renal impairment, though data on end stage liver and kidney disease is limited.[57]

The medicine is administered subcutaneously in the thigh or arm, once a week, without any relation to the food. It should never be given as intravenous or intramuscular injections. The site of administration must be rotated. In case of a missed dose, if the duration is less than 96 hour, then take the dose as soon as possible with the next dose at its usual time.[58] If the duration is more than 96 hour, skip the dose and take the next dose at the scheduled time.[58] The day of weekly administration can be changed as long as there is more than 72-hour spacing between the two doses.

Recommendations

B.1 Pharmacotherapy should be considered in patients with BMI >27 kg/m² or in individuals with a BMI >25 kg/m² with at least one associated comorbid medical condition such as hypertension, dyslipidemia, type 2 diabetes (T2DM), and obstructive sleep apnea:

• Tirzepatide should be considered where a weight loss target of 15%–20% is targeted

• Both tirzepatide and injectable semaglutide should be considered where a weight loss target of only 10%–15% is targeted.

SECTION C – COUNSELLING FOR ANTI-OBESITY MEDICATIONS

Medication counseling is an integral part of anti-obesity medication usage.[59] Such counseling is required not only prior to prescription, but during therapy as well. The nature and intensity of medication counseling may vary according to the type and dose of drug being suggested. However, the basic principles of patient education remain the same. We use the BLACK format to suggest a simple framework for anti-obesity medication counseling.[60] This can be used by endocrinologists, physicians and paramedical personnel alike.

Benefits

One must give time to the person living with obesity, and their caregivers, to contemplate the use of medication. This contemplation will vary from person to person, and situation to situation. The duration and depth of the relationship with the treating physician/health care team influences the need for contemplation, as does the degree of distress due to obesity.

The potential benefits, and mechanism of action of drugs, must be shared in a person-friendly manner. The importance of weight loss, as well as glucose control, cardiovascular benefit, and renal health, can be explained using locally relevant examples, similes and metaphors.[61]

Limitations

Anti-obesity medications are just one part of the management strategy for obesity. Their use does not obviate the need for dietary restriction and regular exercise. Continued efforts at managing comorbidities and complications of obesity are also required, along with weight-lowering drugs.[62]

A reality check is also necessary while initiating or intensifying therapy for obesity. The expected trajectory of weight loss/maintenance can be predicted from the results of randomized controlled trials. This can be shared with individuals contemplating obesity treatment. The possibility of inter-individual variability must be explained. While the need for long term weight therapy is well-known, a suggestion for finite therapy (three months), to assess the efficacy and tolerability of a particular drug, can be made.

Adverse effects

The possibility of adverse effects, especially gastrointestinal symptoms, must be mentioned during counselling. Reassurance that these complaints (nausea, diarrhoea, dyspepsia) are usually mild and transient, and suggestions to mitigate them [Table 6], help in reducing the distress due to these symptoms. A careful evaluation to rule out conditions such as gastroparesis and gall bladder disease, can help reduce the risk of drug-related adverse events. Persons should be told that these effects are a sign that the drug has begun acting.

Table 6.

Mitigation of GLP1RA-related adverse events

Counselling

• Explain possibility of adverse events in advance

• Use non-threatening, positive tone while discussing adverse event

• Highlight that such events are usually mild and transient

• Reassure that these events can easily be managed

Dietary advice

• Take small, frequent meals

• Avoid high carbohydrate, high fat, and high fibre meals

• Avoid aerated/carbonated beverages

• Avoid alcohol

Comfort food/spices

• Consider ginger candy, liquorice, cloves, fennel seeds to prevent/manage nausea

• Consider ice cubes, ice candy to prevent/manage nausea

• Try non-aerated/non-carbonated beverages, such as buttermilk, kokum juice, in small quantities

GLP1RA use

• Begin with low doses

• Up titrate slowly

• Inject daily GLP1RA at night

• Begin/intensify GLP1RA during the follicular, rather than luteal, phase, in menstruating women

Concomitant medication

• Reduce the use of other glucose lowering drugs medication that may cause gastrointestinal side effects for example metformin, acarbose, voglibose, imeglimin

• Minimize the use of medications that may cause gastrointestinal side effects, for example opioids, iron, calcium

• Avoid initiation/intensification of GLP1RA along with short courses of drugs such as antibiotics, antipyretics: delay such initiation/intensification till the acute illness is resolved

• Consider changing time of administration of other drugs, as per patient convenience

Corrective management

• Use appropriate therapy to manage nausea and vomiting for example ondansetron

• Use appropriate therapy for dyspeptic symptoms, for example proton pump inhibitors, rebamipide

• Consider using pre-/pro-biotics to manage gastrointestinal symptoms such as diarrhea

• Consider prokinetic drug prucalopride, to manage constipation

Cost

Cost is an important determinant of health care acceptance and adherence, especially in pay-from-pocket settings. This must be addressed at the beginning. A cost: benefit analysis of anti- obesity medication price versus the economic impact of obesity, and its complications, helps in decision making.

The use of anti-obesity medication allows reduction of other glucose-lowering or blood pressure-lowering therapy, thus leading to overall cost reduction.

Pragmatic prescriptions, or flexible pharmacotherapeutics, with lower or less frequent doses, may be proposed to reduce cost. It must be noted, however, that these methods are not backed by evidence.

Knowledge

For any medication to be effective, self-care and self-management is mandatory. Persons taking therapy for obesity should be equipped with the necessary skills to optimize their attitude, behaviour and choices.[63]

They should also be taught the right method of medication administration. Techniques for self-injection of subcutaneous drugs, screening and prevention of local site reactions, and avoidance of lipohypertrophy must be explained.

Contraception is mandatory in women of child bearing age, who plan to start anti-obesity medication or undergo bariatric surgery. This must continue for 3 months after cessation of medication, and 12–18 months after bariatric surgery. Women on oral contraceptives must shift to a non-oral method (such as progesterone containing intra uterine contraceptive device), or add a barrier method, when tirzepatide is initiated or intensified.[64]

Micronutrient supplementation may be required in some cases. Examples include persons on restricted diets, such as vegan or vegetarian diets, and those with higher requirements, for example adolescents.

General approach

Medication counseling, and motivational tactics, should be integrated into obesity practice. All members of the obesity care team should be trained in motivational therapeutics and counseling skills. Repeated counseling is required: obesity care professionals should understand that this adds value to their prescription (value added therapy).

Therapeutic planning should be based on informed, and shared decision making. Adequate medication counseling, before and during treatment, ensures that the person with obesity feels respected, and responded to. Thus, obesity medicine can be practiced in a person- centred, and person-friendly, manner. This, in turn, fosters patient satisfaction, and ensures achievement of optimal therapeutic outcomes.

Recommendations

C.1 Proper counselling for anti-obesity medications must precede their usage. The counselling should continue during the treatment.

C.2 Benefits, limitations, adverse effects, and cost of the anti-obesity medications should be a part of the counselling.

C. 3 Patients should be educated about the correct method of administering anti-obesity medications.

C.4 Counselling for contraception in women of child bearing age is essential before starting anti -obesity medications.

SECTION D - SOCIAL MANAGEMENT OF OBESITY

Obesity is increasingly recognized not just as a medical condition but as a ‘social syndrome’ that reflects broader societal issues. The rising prevalence of obesity globally indicates that it is influenced by various social determinants, including economic status, education, and cultural norms. For instance, socioeconomic disparities often lead to unequal access to healthy food options and recreational facilities, exacerbating the obesity epidemic among lower-income populations.[65] To assess socioeconomic status, the Kuppuswamy Scale may be utilized.[66]

Family support systems can play an important role in adherence to lifestyle interventions. These support systems can be evaluated using validated scales designed specifically for measuring family dynamics related to health behaviours. The Family Health Behaviour Scale (FHBS) is one such tool that consists of 27 items assessing parental behaviour regarding meal routines, physical activity levels, and children’s health behaviours related to obesity management.[67] Similar tools for adults need to be developed.

The involvement of family members in clinical visits can be beneficial. Engaging family members in clinical appointments can enhance the support system for individuals undergoing obesity treatment. Research indicates that parental involvement is crucial for improving weight outcomes in children and adolescents.[68] Family-based interventions can lead to better adherence to dietary changes and physical activity recommendations.

Incorporating family dynamics into treatment plans can address dysfunctional behaviours that contribute to obesity. Family Systems Theory (FST) suggests that healthy behaviours are influenced by family interactions; thus, involving the entire family in treatment may yield better outcomes than focusing solely on the individual.[69] Further, intensive behavioural therapy programs that include family members have shown promise in promoting healthier lifestyle changes by reinforcing positive behaviours at home.

Establishing community support networks where individuals share experiences, challenges and successes in their weight management journeys can foster a sense of community engagement. Peer support groups consisting of other individuals attempting lifestyle change can encourage healthy behaviours. Similarly, some suggesting that social networks can reinforce unhealthy eating habits or sedentary lifestyles and should be avoided.[70]

Community engagement in health promotion activities can foster supportive environments that encourage healthier lifestyle choices.[8] Community-based exercise sessions in parks or public spaces where individuals can participate in group workouts or yoga sessions can foster social connections among participants. Peer-led exercise groups can encourage accountability among members, who meet regularly for activities like walking or running enhancing commitment to fitness goals. In this respect, traditional games such as kabaddi kho kho can be integrated into community activities to promote physical fitness while respecting cultural heritage. Practices like yoga, folk dance, martial arts, religious pilgrimages can foster sense of community while encouraging active lifestyles. Wherever feasible, local religious leaders can be involved in enhancing community outreach efforts by promoting healthy lifestyle choices within congregations.

Recommendations

D.1 Socioeconomic status of the obese patient should be considered while advising management of obesity.

D.2 Family support systems must be assessed while advising management of obesity.

D.3 Spouse and family members should be engaged in clinical appointments so that they can be educated regarding healthy diet and activity and serve as a support system for individuals undergoing obesity treatment.

D.4 If available, community support networks should be leveraged where individuals can interact with other persons living with obesity.

D.5 Participation in community-based or peer led exercise groups should be encouraged.

CONCLUSION

The current manuscript is an update to the previously published clinical practice guidelines published by the endocrine society of India. This should be read and implemented in clinical practice together with the previous version and may not suffice to provide a comprehensive management protocol for management of obesity in people living within India. This covers the recent epidemiological trends, newer medications and the advice that should be given when prescribing these medications. Though these guidelines provide the most updated literature on obesity management, it is important to note that no same management protocol fits for all people living with obesity. The treatment plan must be individualized and based on principles of person cantered care.

Authors’ contribution

All authors contributed equally to the manuscript.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence

Artificial Intelligence was not used in writing or preparation of the manuscript.

Funding Statement

Nil.