Pharmacological management of obesity: Current landscape and emerging therapies

Abstract

Obesity is now recognized as a chronic, multifactorial, and progressive disease as opposed to mere excess of body weight. It significantly increases the risk of type 2 diabetes, cardiovascular disease, metabolic-associated fatty liver disease, and mental health disorders. 2022 data reveal that nearly 3 billion individuals worldwide were living with either obesity or overweight. Pharmacological therapy has evolved remarkably. Earlier medications targeted primarily the brain’s monoaminergic pathways but they were withdrawn due to safety concerns. Currently, six medications (Orlistat, Phentermine/Topiramate, Naltrexone/Bupropion, Liraglutide, Semaglutide, and Tirzepatide) are approved by the U.S. Food and Drug Administration for long-term obesity management and among these, glucagon-like peptide receptor agonists have revolutionized the therapy. The emerging pipeline is even more promising. It has new dual and triple combinations such as CagriSema, Survodutide, and Retatrutide for better efficacy and metabolic outcomes, as well as long-acting and oral formulations, which will improve adherence and accessibility. India released its new obesity guideline in January 2025, emphasizing on early pharmacotherapy initiation and the adoption of stage-based obesity classification. Together, these developments signify a transformative era in obesity care where pharmacotherapy is a powerful and evidence-based tool that, in many cases, approaches the efficacy and metabolic benefits traditionally associated with bariatric surgeries.

The Weight of the Problem

Today, obesity is not just about extra weight; it is being recognized globally as a chronic, multifactorial disease. As of 2022, almost 3 billion people across the world were living with either overweight or obesity, which included over half a billion women and almost 400 million men.[1] Even the number of children and adolescents affected has increased tenfold since 1975. India, too, has not been spared.[1] Recognizing this growing public health crisis, March 4 is observed globally as World Obesity Day, a day dedicated to raising and strengthening awareness and inspiring multidisciplinary actions to address obesity.

Our understanding of obesity is also progressing. In 2025, The Lancet Diabetes and Endocrinology Commission redefined obesity by shifting from merely excess weight to excess adiposity, with or without abnormal distribution or function of adipose tissue. They suggested two classifications: Preclinical Obesity, where excess adiposity is present, but tissue and organ function remain preserved, although the risk of progressing to clinical obesity and several other noncommunicable diseases is elevated, and clinical obesity, where adiposity has already caused dysfunction at the tissue, organ, or systemic level.[2] Notice that the term “overweight” is gradually disappearing from clinical language, reflecting a focus on pathophysiology and adverse health effect caused by obesity rather than the appearance. This evolution in definition highlights why calling obesity a lifestyle problem is misleading because in reality it is a chronic progressive disease which significantly increases the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), metabolic associated fatty liver disease (MAFLD), polycystic ovarian syndrome, osteoarthritis, and mental health disorders, among many others, and hence obesity has been given the term ABCD which stands for adiposity-based chronic disease.[3]

In this narrative review, we will explore the rapidly evolving field of obesity pharmacotherapy, starting with a brief history of withdrawn antiobesity medications, then exploring the currently approved drugs that form the cornerstone of modern obesity care, and finally moving into the exciting future pipeline of therapies that aim to re-engineer metabolic regulation in innovative ways. Along the way, we will also see how these medications work inside our body and how India is integrating these advances into clinical practice through the release of updated guidelines in January 2025 (after ~ 16 years), tailored to its population. The journey ahead highlights a future where obesity care is smarter, more effective, and more personalized than ever before.

The Cautionary Tale of Withdrawn Drugs

Since 1964, 26 different drugs have been withdrawn. Most of them targeted the brain’s monoamine pathways. About 80% were withdrawn due to concerning case reports related to adverse events (psychiatric disturbances, cardiac toxicity, risks of abuse). Seven drugs of those 26 have been linked with deaths: aminorex, benfluorex, fenfluramine, methamphetamine, phentermine, rimonabant, and sibutramine, but only two of these (fenfluramine and desfenfluramine) are banned globally. The rest are still being used in some parts of the world, showing us how differently regulators weigh risks and benefits.[4]

The Current Line-up: U.S. Food and Drug Administration Approved Drugs

After decades of trial and error, six drugs (Orlistat, Phentermine/Topiramate, Naltrexone/Bupropion, Liraglutide, Semaglutide (injectable and oral formulation), and Tirzepatide) currently have approval for long-term obesity treatment [Tables 1 and 2]. Phentermine is also approved, but for short-term use (≤12 weeks) only in individuals over 16 years old. Apart from these approved medications, there are drugs that are used off-label for the treatment of obesity, such as oral semaglutide (Rybelsus), dulaglutide, etc.

Table 1.

Overview of food and drug administration anti-obesity drugs

Drug	Mechanism of action	Year of approval	Brand name	Trials	Minimum age (years)	Developer company
Orlistat[5]	Reversible lipase inhibitor	1999	Xenical, Alli	XANDOS	12	Roche
Phentermine + topiramate[6]	Sympathomimetic amine + GABA agonist and Glutamate antagonist	2012	Qysmia	EQUIP, CONQUER, SEQUEL	12	Vivus
Naltrexone + bupropion[7]	Opioid antagonist + NDRI	2014	Contrave	COR	18	Orexigen
Liraglutide[8]	GLP-1 agonist	2014	Saxenda	SCALE	12	Novo Nordisk
Semaglutide (injectable formulation)[9]	GLP-1 agonist	2021	Wegovy	STEP	12	Novo Nordisk
Tirzepatide[10]	GLP-1 + GIP agonist	2023	Zepbound	SURMOUNT	18	Lilly
Semaglutide (oral formulation)	GLP-1 agonist	2025	Wegovy	OASIS	18	Novo Nordisk

GABA=Gamma-aminobutyric acid, NDRI=Norepinephrine-dopamine reuptake inhibitor, GLP-1=Glucagon-like peptide 1, GIP=Glucose-dependent insulinotropic polypeptide

Table 2.

Eligible population, administration and formulation details, and major adverse effects of food and drug administration -approved anti-obesity medications

Drug	Eligible population	Dosage and administration	Route and frequency	Available formulations and strengths	Major adverse effects
Orlistat[5]	Adults and adolescents ≥12 years with BMI≥30 kg/m2 (obese) or≥27 kg/m2 (overweight) with comorbidities (e.g., hypertension, diabetes, dyslipidemia)	120 mg capsule three times daily with each main meal containing fat (during or up to 1 h after the meal)	Oral, three times daily with meals	Capsules: 120 mg (Xenical), 60 mg (Alli, OTC)	GI upset
Phentermine + topiramate[6]	Adults with BMI≥30 kg/m2, or ≥27 kg/m2 with ≥1 weight-related comorbidity; Pediatric ≥12 years with BMI ≥95th percentile for age and sex	Start 3.75 mg/23 mg daily for 14 days, then 7.5 mg/46 mg daily; may escalate based on response to 11.25 mg/69 mg or 15 mg/92 mg	Oral, once daily in the morning, with or without food	Extended-release capsules (phentermine mg/topiramate mg): 3.75/23 mg, 7.5/46 mg, 11.25/69 mg, 15/92 mg	Adults: Constipation, dysgeusia, paresthesia, dizziness, insomnia, dry mouth Pediatric: Depression, dizziness, pyrexia, arthralgia, influenza
Naltrexone + bupropion[7]	Adults with BMI ≥30 kg/m2 or ≥27 kg/m2 with ≥1 comorbidity (e.g., hypertension, diabetes, dyslipidemia)	Week 1: 1 tab morning Week 2: 1 tab morning + 1 tab evening Week 3: 2 morning + 1 evening Week 4 onward: 2 morning + 2 evening	Oral, as mentioned in the previous column, with or without food but not with a high-fat meal	Extended-release tablets: 8 mg naltrexone HCl/90 mg bupropion HCl	GI upset, headache, dizziness, insomnia, dry mouth
Liraglutide[8]	Adults with BMI ≥30 kg/m2, or ≥27 kg/m2 with comorbidities; pediatric ≥12 years with body weight >60 kg and BMI ≥30 kg/m2 (adult equivalent)	Start 0.6 mg daily, increase by 0.6 mg weekly to a maintenance dose of 3 mg daily	Subcutaneous, once daily (abdomen, thigh, or upper arm)	Injection: 6 mg/mL solution in 3 mL prefilled pen delivering 0.6, 1.2, 1.8, 2.4, or 3 mg doses	GI upset, fatigue, headache, dizziness, hypoglycemia, pyrexia, injection site reactions, increased lipase
Semaglutide (injectable formulation)[9]	Adults with BMI ≥30 kg/m2, or ≥27 kg/m2 with comorbidities; pediatric ≥12 years with BMI ≥95th percentile for age/sex	Start 0.25 mg weekly for 4 weeks, increase every 4 weeks to 2.4 mg weekly (maintenance: 1.7 mg or 2.4 mg)	Subcutaneous, once weekly (abdomen, thigh, or upper arm)	Injection: Prefilled, single-dose pens delivering 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, or 2.4 mg	GI upset, GERD, fatigue, headache, dizziness, nasopharyngitis
Tirzepatide[10]	Adults with BMI ≥30 kg/m2, or ≥27 kg/m2 with ≥1 comorbidity (e.g., hypertension, diabetes, dyslipidemia, OSA, CVD)	Start 2.5 mg weekly for 4 weeks, then 5 mg weekly; increase by 2.5 mg increments every ≥4 weeks up to 15 mg weekly	Subcutaneous, once weekly (abdomen, thigh, or upper arm)	Injection: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg per 0.5 mL in single-dose pen or vial	GI upset, GERD, injection site reactions, fatigue, hair loss, hypersensitivity reactions
Semaglutide (oral formulation)[11]	Adults with BMI≥30 kg/m2, or≥27 kg/m2 with≥1 comorbidity	Days 1–30: 1.5 mg once daily Days 31–60: 4 mg once daily Days 61–90: 9 mg once daily Day 91 onward: 25 mg once daily	Oral, once daily in the morning, empty stomach	Tablets: 1.5 mg, 4 mg, 9 mg and 25 mg	GI upset, GERD, fatigue, headache, dizziness, nasopharyngitis

BMI=Body mass index, OTC=Over the counter, GI=Gastrointestinal, GERD=Gastroesophageal disease, OSA=Obstructive sleep apnea, CVD=Cardiovascular disease

Recently approved oral semaglutide was investigated in the OASIS program and is considered a milestone in obesity pharmacotherapy as it offers an oral incretin-based option for the first time, which will be a huge boost to accessibility and adherence. In the 68-week OASIS 1 trial, the 50 mg once-daily dose led to a 15.1% mean weight reduction versus 2.4% with placebo,[12] while in the OASIS 4 trial, the 25 mg dose showed 13.6% reduction versus 2.2% with placebo.[13] Since the 25 mg oral formulation showed similar efficacy to 2.4 mg subcutaneous semaglutide used in the STEP 1 study, it was submitted to the U.S. Food and Drug Administration (FDA) for review, which has now been approved for chronic weight management.[14,15]

Growing Market Presence of Incretin-based Therapies

These medications have become a central part of metabolic care. In the global Top 200 Drugs by Retail Sales analyses, Semaglutide secured third position in both 2023 and 2024, while Tirzepatide climbed from 22^nd place in 2023 to 9^th place in 2024.[16,17] These drugs have other indications as well, but their growing use in obesity treatment has clearly contributed to their rising visibility and sales, suggesting that incretin-based therapies will continue to grow and may become one of the most financially successful drug classes in the years to come.

A Brief History of Incretins

Before exploring the mechanisms of incretin-based therapies, it is worth revisiting how these hormones first came into focus. In 1906, early experiments showed that extracts from the small intestine could influence pancreatic function, leading to researchers thinking that the gut releases substances that stimulate insulin secretion.[18] This concept was formally named in 1929 when Zunn and LaBarre introduced the term “incretin” to describe molecules released from the gut that increase pancreatic endocrine activity.[19] The importance of incretins became clearer in the 1960s with the description of the “incretin effect” (an observation that oral glucose produces a much greater insulin release than the same amount of glucose given intravenously).[20] This finding showed that hormones released from the gut play a key role in insulin secretion after meals. As several gut peptides were being discovered during this period, clear criteria were proposed to define an incretin hormone. First, the hormone should release following oral glucose intake, and second, it should stimulate insulin secretion when administered intravenously at plasma concentrations comparable to those achieved after oral glucose ingestion. These criteria provided a framework for identifying true incretin hormones.[21] Further research identified glucose-dependent insulinotropic polypeptide (GIP) as the first incretin hormone; however, GIP alone could not fully explain the incretin effect, indicating that additional gut hormones were involved.[22] Further insight came from studies of glucagon-related peptides. The identification of N-terminal fragments of glicentin in pancreatic α-cells suggested that multiple peptides could arise from a common precursor, leading to the concept of differential processing of proglucagon in the pancreas and the gut. This concept was firmly established in 1983 when Bell et al. published the complete structure of human proglucagon. Their work showed that in addition to glucagon, oxyntomodulin, and glicentin, the proglucagon molecule also contains two other glucagon-like peptides (GLPs), GLP-1 and GLP-2.[23] Subsequent studies revealed that it is GLP-1 that fulfilled the criteria of an incretin hormone. It increased glucose-dependent insulin release and inhibited glucagon release, slowed gastric emptying, and reduced appetite. These properties established GLP-1 as a central regulator of metabolic control and laid the foundation for the development of incretin-based therapies that now play a key role in the management of diabetes and obesity.

Mechanisms of Incretin-based Therapies

The remarkable effectiveness of incretin-based therapies is due to their ability to interact both centrally and peripherally, thereby influencing various physiological mechanisms of the body.

Central pathways

GLP-1 receptors (GLP-1Rs) are present in brain areas which are responsible for regulating appetite and reward. These include the hypothalamus, brainstem nuclei (such as the nucleus tractus solitarius), and mesolimbic regions like the ventral tegmental area and nucleus accumbens. When GLP-1Rs in these areas get stimulated, they promote feeling of satiety, reduce appetite, and make foods less desirable. At the same time, GLP-1 stimulation in the brainstem and reward circuits reduces hedonic eating.[24]

Peripheral pathways

GLP-1 slows gastric emptying, causing a prolonged sense of fullness after meals along with increasing the release of various other hormones that promote satiety, including ghrelin, peptide YY (PYY), and cholecystokinin. In the pancreas, it stimulates glucose-dependent insulin release while inhibiting glucagon, resulting in more consistent blood glucose levels. It reduces inflammation and improves lipid metabolism in adipose tissue and the liver, resulting in a reduction of accumulated fat.[24]

Beyond single hormones

Dual and triple agonists take this concept a step further. Combining GLP-1 with GIP agonists/antagonists and/or glucagon agonists provides a powerful combo to regulate hunger, improve insulin release and lipid metabolism, and energy consumption.[24] Collectively, these signals lead to a more significant weight reduction and metabolic wellness than any individual pathway could accomplish on its own.

Both Glucose-dependent Insulinotropic Polypeptide Receptor Agonism and Antagonism Contribute to Weight Loss?

The answer is yes! Although it may seem counterintuitive, they achieve this through distinct pathways. GIP receptor (GIPR) agonists work by directly activating GABAergic GIPR⁺ neurons in the brain. This activation suppresses food intake and promotes weight loss. In mice lacking GIPR, these effects are completely abolished, whereas the effects remain intact in mice lacking GLP-1Rs. GIPR antagonists, on the other hand, do not act through direct GIPR signaling in GABAergic neurons as they need an intact GLP-1R pathway to have an effect. By blocking the inhibitory influence of non-GABAergic GIPR⁺ neurons, GIPR antagonism disinhibits downstream GLP-1R⁺ neurons, resulting in increased anorectic effects of GLP-1 signaling.[25]

The Pipeline: What’s Next?

The pipeline for antiobesity drugs is no longer a narrow stream but a branching river, with multiple currents flowing from a common source, the incretin revolution. Much like the layered progression described in leading reviews, it can be seen as waves of innovation, each building upon the last [Table 3].

Table 3.

Pipeline of investigational anti-obesity drugs and their current clinical trial status

Drug Class	Drug	Phase of Clinical Trial
Oral GLP-1 agonist	Orforglipron	Phase 3 completed
	Ecnoglutide	Phase 1 completed
	CT 996	Phase 1 completed
Injectable GLP-1agonist	Semaglutide 7.2 mg	Phase 3 completed
GIP agonist	ZP 6590	Phase 0 completed
GLP-1 + GIP agonist	VK 2735	Phase 2 ongoing
	CT 388	Phase 2 ongoing
GLP-1 + GIP antagonist	MariTide	Phase 3 ongoing
Glucagon agonist	HM 15136	Phase 1 completed
GLP-1 + glucagon agonist	Survodutide	Phase 3 ongoing
	Mazdutide	Phase 3 completed
	Pemvidutide	Phase 2 completed
	AZD 9550	Phase 2 ongoing
	DA 1726	Phase 1 ongoing
GLP-1 + GIP + glucagon agonist	Retatrutide	Phase 3 ongoing
Amylin agonist	Cagrilintide	Phase 3 completed
	Petrelintide	Phase 2 ongoing
	AZD 6234	Phase 2 ongoing
	LY 3841136	Phase 2 ongoing
GLP-1 + Amylin agonist	CagriSema	Phase 3 completed
	Oral amycretin	Phase 2 ongoing
PYY agonist	Nisotirostide	Phase 2 ongoing
GLP-1 + PYY agonist	NNCO165-1875 + Semaglutide	Phase 2 completed
	NNCO165-1562 + Semagltuide	Phase 1 completed
Different mechanism from hormone-based	Monlunabant	Phase 2 completed
	Bimagrumab	Phase 2 ongoing
	GDF-15	Phase 1 completed
	LY 354105	Phase 2 ongoing
	GSBR 1290	Phase 2 ongoing

GLP-1=Glucagon-like peptide 1, GIP=Glucose-dependent insulinotropic polypeptide, PYY=Peptide YY

Continuing with Glucagon-like Peptide-1 Agonism

Orforglipron is a once-daily nonpeptide GLP-1R agonist, which might be a game-changer in the treatment of obesity due to its cost. In a 72-week phase 3 trial (ATTAIN-1), it achieved a mean weight loss of 7.5%–11.2% across doses (6, 12, and 36 mg) compared with 2.1% with placebo.[26] Another advantage is that it has no drug-food interaction and so can be taken anytime during the day.

The GLP-1 story continues with high-dose injectable semaglutide (7.2 mg weekly), which was evaluated in the STEP UP phase 3 trial, where participants without diabetes had an 18.7% mean weight loss at 72 weeks compared to 15.6% loss seen with standard 2.4 mg dosing. This “super-dose” had a comparable safety profile, thus providing an option for those individuals who may respond inadequately to lower doses.[27]

Newer Dual Combinations

Two dual GLP-1/glucagon agonists (Survodutide and Mazdutide) have also demonstrated meaningful results. Survodutide (0.6, 2.4, 3.6, and 4.8 mg) achieved 6.2%–14.9% mean weight reduction over 46 weeks, whereas Mazdutide led to 11% and 14% loss with 4 mg and 6 mg doses, respectively, in the GLORY-1 trial.[28,29] Both agents also improved hepatic and metabolic parameters which shows that they might be helpful in patients who have developed MAFLD as a complication. Another innovation is MariTide. It is a GLP-1 agonist (Cafraglutide), which is combined with a GIP antagonist (Maridebart). This combination reduced weight by around 2.3%–16.2% in nondiabetic and 8.4%–12.3% in diabetic participants after 52 weeks in its phase 2 study. One big advantage with this combo is that it needs to be administered once a month only, which will indeed improve adherence and patient convenience.[30] It is now being evaluated in a phase 3 program called MARITIME. Next in line, we have amylin-based therapies. CagriSema is a combination of semaglutide (2.4 mg) and cagrilintide (2.4 mg), which achieved 20.4% mean weight loss at 68 weeks in the REDEFINE-1 trial, showing superiority over both monotherapies.[31] In the phase 3 REDEFINE-4 trial, which directly compared CagriSema with Tirzepatide, CagriSema was not able to achieve noninferiority against tirzepatide (both administered once weekly, subcutaneously). The combination of semaglutide and cagrilintide (2.4 + 2.4 mg) achieved a 20.2% weight loss versus 23.6% achieved with tirzepatide 15 mg.[32]

Triple Agonist

From single hormones to multi-pathway agents, combination incretin therapies are redefining efficacy. Tirzepatide (dual GLP-1/GIP agonist) has already achieved 20%–22% weight reduction in phase 3 trials. The next molecule which has the potential for even more weight reduction is retatrutide. It is a triple agonist acting on GLP-1, GIP, and glucagon receptors, which has shown up to 24.2% mean weight loss at 48 weeks in phase 2 trials compared to 2.1% with placebo.[33] Currently, TRIUMPH phase 3 studies and a head-to-head comparison with tirzepatide (TRIUMPH 5) are ongoing, which will determine whether retatrutide sets a new benchmark for nonsurgical weight loss or not.

Nonhormonal Based Therapies

Alternative mechanisms (other than incretin-based therapies) are also being explored. First lets talk about Monlunabant. Monlunabant is a cannabinoid-1 receptor inverse agonist which achieved a mean weight loss of 6.4–8 kg versus placebo at 10, 20, and 50 mg over 16 weeks in a phase 2a study, with higher doses offering minimal additional benefit.[34] Another molecule is Bimagrumab, a monoclonal antibody which targets activin II receptors, has shown 6.5% weight reduction while increasing lean body mass by 3.6%. This is something unique to bimagrumab, as other agents have not been able to preserve lean body mass, which might be valuable for older adults or those at risk of sarcopenia.[35]

Finishing our list with some other early-phase agents which are currently being explored include long-acting amylin analogues, PYY agonists, and GDF-15 mimetics. Their efficacy is still uncertain, but they are adding to the evidence that there is going to be a more diverse future where treatments can be matched to individual needs. Apart from all these pipeline therapies which are competing to improve efficacy in adults, researchers have also started to shift their focus toward childhood obesity. A pivotal example is the SCALE Kids trial, where liraglutide was evaluated in children aged 6 to <12 years with obesity, and it showed an average body mass index (BMI) reduction of 4.2% points greater than placebo.[36]

The current landscape of obesity treatment has evolved into a multifaceted system. We now have oral GLP-1 therapies, which will improve adherence and accessibility, higher dosing strategies to boost efficacy, more dual or triple combinations to maximize weight loss and provide longer dosing intervals. Researchers are also exploring new molecules which might help us reshape our body composition or serve niche clinical needs. All these advances signify that we are pushing pharmacological solutions to reach transformative outcomes we once thought were possible only through bariatric surgery.

Indian Context

In India, the treatment landscape has its own character. Only four of the six FDA-approved drugs are currently available: Orlistat, liraglutide, semaglutide (injectable formulation), and tirzepatide. Oral semaglutide is not formally approved for obesity but is being used off-label. In addition, although Zepbound (tirzepatide) is approved for obesity, the currently available formulation in India is Mounjaro (tirzepatide), which is approved for diabetes, but is being used to treat obesity as well.

Cost and access are important considerations in the Indian context. Incretin-based therapies such as semaglutide and tirzepatide are associated with significant out-of-pocket expenditure. In India, the cost of semaglutide (Wegovy) is around ₹10,000–₹17,000/month, depending on dose, while that of tirzepatide (Mounjaro) is around ₹13,000–₹26,000/month across different dose strengths.[37] Since obesity requires long-term treatment, affordability becomes a serious practical concern for many patients. Insurance coverage for outpatient medications remains nonexistent in India unlike the U.S., Europe and other developed countries. Therefore, adoption within government hospitals and primary care settings does not seem feasible in the foreseeable future. As a result, use is currently concentrated in private urban specialty practices, particularly endocrinology and general medicine clinics.

Even guidelines are evolving. In January 2025, a new guideline for the Indian population emerged after ~16 years, which classified obesity into two stages, as illustrated in Figure 1 [Refer to Table 4 for updated clinical assessment parameters and diagnostic cutoffs for obesity]. Patients in Stage 1 respond well to lifestyle modifications alone, but medication is advised if weight gain occurs by >10% even after lifestyle measures or if BMI is ≥27.5 or if the patient is likely to progress to Stage 2 (e.g. at risk for developing T2D or CVD). In Stage 2, where the risks of systemic illness are high, pharmacotherapy should be started as soon as possible along with lifestyle modifications to prevent further progression. In individuals without T2D, orlistat is the recommended drug and in individuals with T2D, atherosclerotic CVD, high grades of BMI, and MAFLD, GLP-1R agonists are the first-line drugs.[38] A key update in the guideline is that “stage” and “grade” represent two different dimensions of obesity, with stage telling us about the clinical severity and risk of complications (Stage 1 vs. Stage 2) while the grade depicting the BMI range within that stage, helping us classify obesity with more precision. For example, a person with a BMI of 27 kg/m² without any comorbidities or functional limitations can be classified as Stage 1 Obesity with Grade 2 BMI, showing that someone can be in Stage 1 (lower clinical risk) while having a higher BMI within that stage.

Figure 1.

Classification of obesity.[38] BMI: Body mass index

Table 4.

Clinical assessment parameters and diagnostic cutoffs for obesity in the Indian population

Measurements	Cutoffs
Body fat percentage*	Men: >25.5 Women: >38
BMI grades (kg/m2)	Normal: 18.5–22.99
	Grade I: 23–24.9
	Grade II: 25–27.5
	Grade III: 27.6–32.4
	Grade IV: ≥32.5
Abdominal obesity#
WC (cm)	Men: ≥90
	Women: ≥80
W-HtR	>0.5
Functional symptoms	Shortness of breath, palpitations, and musculoskeletal symptoms like pain in lower limb joints on doing activities within the house, bathing, dressing, toileting, eating, etc.
Obesity-related comorbidities	T2D, CVD, OSA, metabolic dysfunction-associated fatty liver disease, dyslipidemia, hypertension, osteoarthritis (lumbosacral spine and lower limbs), mental health disorders (depression, anxiety, and low self-esteem), infertility, male hypogonadism, lower limb edema, and PCOS

*Gold standard for diagnosing obesity, ^#WC is the best measure for abdominal obesity. W-HtR may be useful to indicate abdominal obesity and should be preferred over the W-HR. W-HR=Waist-to-hip ratio, W-HtR=Waist-to-height ratio, WC=Waist circumference, BMI=Body mass index, T2D=Type 2 diabetes, CVD=Cardiovascular disease, OSA=Obstructive sleep apnea, PCOS=Polycystic ovarian syndrome

A point worth highlighting again is that the terms “overweight” and “preobesity” are no longer to be used. Instead, the condition is classified as either Stage 1 or 2 obesity. Furthermore, the waist-to-hip ratio is no longer recommended for diagnosis.

Looking ahead, an upcoming development is the expiry of injectable semaglutide’s patent in India on March 20, 2026 (Indian Patent No. 262697), which will allow Indian pharmaceuticals to introduce more affordable versions.[39] This will significantly reduce treatment costs, increase accessibility, and the uptake of pharmacotherapy for obesity and related metabolic conditions across the country.

Closing the Circle

The story of obesity medicines has been one of challenges, steady progress, and cautious hope. Some early drugs showed promise but had to be withdrawn because of safety concerns. Others, especially the incretin-based therapies we use today, have changed what we believed was impossible. These experiences have helped expand our understanding of the disease. Today, obesity is recognized as adiposity-based chronic disease, a complex condition which is influenced by genetics, environment, physiology, and behaviour. This shift in mindset is important because it tells us that obesity is not simply because of overeating or sedentary lifestyle; it is a chronic medical condition that needs long-term, structured care. The rising rates of obesity worldwide are impacting families, health systems and communities. Nearly 3 billion people now live with overweight or obesity, including millions of children. Countries like India are seeing similar trends, which is why new guidelines are coming up which treat obesity as a chronic disease and emphasize that it must be addressed early and long-term. Modern medicines have shown tremendous other benefits apart from weight loss, like improving blood glucose levels, cardiovascular and liver health, musculoskeletal health, mental health and overall quality of life. And the future looks even more promising. New advances in treatment, such as oral drugs, long-acting injections, and new double and triple combinations, will improve adherence and accessibility, along with providing additional health benefits, helping patients achieve better results. Still, we need to stay alert while using these medications, as safety is equally important as is scientific progress. For effective obesity care, we also need to take steps to reduce stigma, develop a supportive healthcare system, emphasize on a healthy lifestyle including good dietary habits, regular exercise and proper sleep. Looking ahead, we are moving toward a future where obesity care is smarter, kinder, and more effective than ever before. The medicines of the future may not only help people lose weight but also prevent complications and improve daily life.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.