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GLP-1 agonists · mechanism / efficacy / real cost
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In one pass Your gut already has a natural I'm full signal. Not this — Ozempic is a side-effect-free weight-loss miracle — Within a year of stopping, about two-thirds of the lost weight comes back, so in effect it is a lifelong drug. About 70% of people have gut side effects, and loss of lean (muscle) mass is higher (STEP 1 extension, Wilding 2022).
Educational content, not medical advice — consult a clinician.
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Chapter 1
What GLP-1 drugs are
Your gut already has a natural I'm full signal. What these drugs do is simple: they amplify that signal and make it last longer in the body, so you do not feel like eating as much.
The signaling molecule is called (glucagon-like peptide-1), and no drug company invented it: every time you finish a meal, L cells in the lower small intestine release it into the blood. An enzyme called DPP-4 acts like scissors that cut it specifically, so it survives only 1–2 minutes. The whole trick of turning it into a drug is changing the molecule so the scissors no longer recognize it, letting it stay in the body for a long time.
It drifts to several places and does one job at each: at the pancreas, it prompts insulin release only when blood glucose is high (so, unlike sulfonylureas, it does not push insulin out regardless of glucose); it holds down glucagon, so the liver sends less sugar into the blood; it slows gastric emptying, so fullness lasts longer; and in the brain's appetite centers (the hypothalamus and brainstem), it directly turns down the still want to eat signal.
If you develop severe, persistent upper abdominal pain (it may spread to the back) with vomiting while taking one of these drugs, stop the drug and get medical care immediately.
The signaling molecule is called (glucagon-like peptide-1), and no drug company invented it: every time you finish a meal, L cells in the lower small intestine release it into the blood. An enzyme called DPP-4 acts like scissors that cut it specifically, so it survives only 1–2 minutes. The whole trick of turning it into a drug is changing the molecule so the scissors no longer recognize it, letting it stay in the body for a long time.
It drifts to several places and does one job at each: at the pancreas, it prompts insulin release only when blood glucose is high (so, unlike sulfonylureas, it does not push insulin out regardless of glucose); it holds down glucagon, so the liver sends less sugar into the blood; it slows gastric emptying, so fullness lasts longer; and in the brain's appetite centers (the hypothalamus and brainstem), it directly turns down the still want to eat signal.
If you develop severe, persistent upper abdominal pain (it may spread to the back) with vomiting while taking one of these drugs, stop the drug and get medical care immediately.
Mechanism · From one minute to one week
The key breakthroughs in turning it into a drug:Exenatide (2005, derived from a lizard's saliva): the first generation, injected twice a dayLiraglutide (brand names Victoza / Saxenda, 2010 / 2014): a fatty-acid side chain was added, stretching the half-life to 13 hours, once a daySemaglutide (Ozempic / Wegovy, 2017 / 2021): stretched further, to a half-life of 165 hours, one injection a weekTirzepatide (Mounjaro / Zepbound, 2022 / 2023): a dual agonist (acting on both the and the GIP receptors), once a week, more potent
Clinical · Who is approved to use them
How the indications expanded:At first, all of them were for type 2 diabetes (brand names Ozempic, Mounjaro)In the US, the weight-loss indication (chronic weight management) was approved in stages: liraglutide in 2014 (Saxenda), semaglutide in 2021 (Wegovy), tirzepatide in 2023 (Zepbound). The threshold is a body mass index () ≥ 30, or BMI ≥ 27 plus at least 1 weight-related comorbidity (type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease)
Which ones are approved in China (the 2024 obesity diagnosis and treatment guideline): orlistat, liraglutide, beinaglutide, semaglutide and tirzepatide, five drugs approved by China's national drug regulator (NMPA) for weight reduction in adults with primary obesity. The brand names above belong to the US market; China's approved list does not map onto them.
China's guideline also sets the threshold for drug treatment differently: not as a BMI number but as a clinical state: overweight with at least one weight-related condition (high blood glucose, hypertension, dyslipidemia, fatty liver, sleep apnea, cardiovascular disease) where lifestyle intervention does not reach the weight-loss target; or obesity already present where lifestyle intervention does not reach the target. The difference between the two approaches: a number lets someone who falls just 0.4 short conclude that this has nothing to do with them.
A few things to get clear first:
This is not a new mechanism. It is a hormone the body already makes, turned into a drug and amplified, with its half-life stretched from 1–2 minutes to 165 hoursIt is not a fat burner or a metabolism booster; at its core it makes you eat less through the satiety signal in the brainDiabetes came first and weight loss second: the weight-loss effect was first observed as a side effect in people with diabetes, and only then were higher-dose weight-loss indications developed
Chapter 2
Why the injection causes weight loss
Why does this injection make you lose weight? The weight-loss effect of receptor agonists does not run through a single pathway; several mechanisms work together, but the one carrying most of the load is the satiety signal in the brain, not a faster metabolism.
The parts of the brain that manage appetite (the hypothalamus and brainstem) are dense with GLP-1 receptors. Activating them with the drug is like turning up the neurons that tell you to stop and turning down the ones that send you to eat. People taking it often say they are less interested in food, feel full after a few bites, and think about snacks less.
In numbers: in the Blundell 2017 crossover trial, 30 adults with obesity took 1.0 mg a week for 12 weeks and ate 24% less energy over the day, when free to eat as they liked, than on placebo (about 700 kcal, −3036 kJ); resting metabolic rate adjusted for lean mass did not differ.
That is why it is easier to stick with than white-knuckle dieting: dieting means wanting to eat and holding back, while on the drug you simply do not want to eat as much.
The parts of the brain that manage appetite (the hypothalamus and brainstem) are dense with GLP-1 receptors. Activating them with the drug is like turning up the neurons that tell you to stop and turning down the ones that send you to eat. People taking it often say they are less interested in food, feel full after a few bites, and think about snacks less.
In numbers: in the Blundell 2017 crossover trial, 30 adults with obesity took 1.0 mg a week for 12 weeks and ate 24% less energy over the day, when free to eat as they liked, than on placebo (about 700 kcal, −3036 kJ); resting metabolic rate adjusted for lean mass did not differ.
That is why it is easier to stick with than white-knuckle dieting: dieting means wanting to eat and holding back, while on the drug you simply do not want to eat as much.
Mechanism · Gastric emptying slows
Mechanism two: the stomach empties more slowlyGastric emptying slows markedly; the effect is strongest when the drug is first started and weakens with long-term useThat explains the early fullness people feel on the drug, and why satiety lasts longerIt is also where side effects come from: food that stays longer in the stomach causes nausea, reflux and bloatingIt matters for surgery and anesthesia: with slow emptying, the stomach may not be empty even after fasting, which raises the risk of aspiration under anesthesia. In 2023 the American Society of Anesthesiologists (ASA) advised stopping weekly formulations 1 week before elective surgery; later guidance from several societies has changed this. If you are having surgery, be sure to tell your surgeon and anesthetist about the drug in advance and follow their plan
Mechanism · The glucose line
Mechanism three: regulating insulin and glucagon (improving blood glucose)Glucose-dependent stimulation of insulin: the blood-glucose peak after meals fallsSuppression of glucagon: fasting blood glucose fallsIn people with type 2 diabetes, (HbA1c) falls markedly, among the larger drops seen with glucose-lowering drugsWeight loss does not depend on the glucose effect: people with obesity who do not have diabetes lose weight too (which is the basis for the weight-loss indication of Wegovy and Zepbound)
Tirzepatide adds one more lever (dual GIP agonism):
GIP (glucose-dependent insulinotropic polypeptide) is another gut hormoneThe two pathways are generally thought to work in synergy: more weight loss, better fat metabolism, and possibly better glucose controlIn clinical trials: the highest-dose group in SURMOUNT-1 lost 20.9% of body weight on average, and the semaglutide group in STEP 1 lost 14.9%. That is a cross-trial comparison, not a head-to-head one: the two trials differed in their populations and design, so the numbers cannot simply be subtracted
Myth · It is not a fat burner
Why it is not a fat burner:The dominant effect is you naturally eat less, not your metabolism speeds upNo data show it raising resting metabolic rate (RMR): in Blundell 2017, RMR adjusted for lean mass did not differ from placebo. In fact, RMR usually falls during weight loss by any method, a result of having a smaller body plus metabolic adaptation, and not something peculiar to drugsInject and lose weight really means inject and eat less; over the long run it still obeys the conservation of energy
For why the brain pushes appetite back up after dieting, see the Leptin Resistance & Body-Weight Set-Point story. In the Sumithran 2011 study (weight lost by diet, not by drug), satiety signals were still low and ghrelin still high a year after the weight loss. GLP-1 drugs hold that pull down while you take them, but they do not remove the defense: once the drug stops, the pull is still there.
Chapter 3
How much weight trials showed
Two large double-blind randomized trials show what these drugs can do, both in adults with overweight or obesity who did not have diabetes:
Semaglutide (STEP 1, Wilding 2021): 2.4 mg a week for 68 weeks cut body weight by 14.9% on average, against 2.4% with placebo; 50.5% of people lost at least 15%, against 4.9% with placeboTirzepatide (SURMOUNT-1, Jastreboff 2022): after 72 weeks, weight fell by 15.0% to 20.9% on average depending on dose, against 3.1% with placebo
There is a layer beyond weight: in people who already had cardiovascular disease but not diabetes, semaglutide cut major cardiovascular events by about 20% (the SELECT trial, , HR, 0.80; 6.5% vs 8.0%). The participants also lost weight, so the trial did not prove a mechanism independent of weight loss.
Two things to remember: it works slowly, and the full effect takes around a year; and every trial paired the drug with diet and exercise guidance, so none of them shows weight loss from lying back and injecting.
Semaglutide (STEP 1, Wilding 2021): 2.4 mg a week for 68 weeks cut body weight by 14.9% on average, against 2.4% with placebo; 50.5% of people lost at least 15%, against 4.9% with placeboTirzepatide (SURMOUNT-1, Jastreboff 2022): after 72 weeks, weight fell by 15.0% to 20.9% on average depending on dose, against 3.1% with placebo
There is a layer beyond weight: in people who already had cardiovascular disease but not diabetes, semaglutide cut major cardiovascular events by about 20% (the SELECT trial, , HR, 0.80; 6.5% vs 8.0%). The participants also lost weight, so the trial did not prove a mechanism independent of weight loss.
Two things to remember: it works slowly, and the full effect takes around a year; and every trial paired the drug with diet and exercise guidance, so none of them shows weight loss from lying back and injecting.
Evidence · Against other ways to lose weight
The weight-loss effect of drugs clearly exceeds that of earlier non-surgical options.What does that mean in practice? In the Look AHEAD trial (in people with type 2 diabetes), intensive lifestyle intervention cut weight by 8.6% at one year and by 6.0% at the end of the study (median follow-up 9.6 years), against 3.5% in the control group. Orlistat, an older weight-loss drug, takes off about 3.1% after subtracting placebo (China's 2024 obesity guideline). With bariatric surgery, in Sweden's SOS study, gastric bypass took off up to 32% at 1–2 years and still 25% at 10 years. GLP-1 drugs bring an option that needs no operation a big step closer to surgery, but the two have not been compared directly.
Chapter 4
Regain, side effects and other costs
A strong effect is not the same as no cost. drugs have six real costs, and any miracle weight-loss drug claim dodges at least half of them.
The biggest is regain after stopping. After you lose weight, the brain does not file it as a success; it files it as starvation. The signals that make you feel full (leptin from fat cells, PYY from the gut) fall, and ghrelin, which makes you feel hungry, rises. A study that followed people for a year after they lost weight by diet (Sumithran 2011) found that these changes had still not returned to their pre-diet levels a year later. While you take the drug, it holds that pull down for you; once it stops, the hunger comes back, most of the lost weight returns, and markers that improved along the way, such as blood pressure and blood lipids, mostly drift back close to where they started.
So these drugs are meant for long-term, possibly lifelong use, not as a course you stop once the weight is off. The other five costs are gut side effects, loss of lean mass, rare but serious adverse events, unknown long-term safety, and money.
The biggest is regain after stopping. After you lose weight, the brain does not file it as a success; it files it as starvation. The signals that make you feel full (leptin from fat cells, PYY from the gut) fall, and ghrelin, which makes you feel hungry, rises. A study that followed people for a year after they lost weight by diet (Sumithran 2011) found that these changes had still not returned to their pre-diet levels a year later. While you take the drug, it holds that pull down for you; once it stops, the hunger comes back, most of the lost weight returns, and markers that improved along the way, such as blood pressure and blood lipids, mostly drift back close to where they started.
So these drugs are meant for long-term, possibly lifelong use, not as a course you stop once the weight is off. The other five costs are gut side effects, loss of lean mass, rare but serious adverse events, unknown long-term safety, and money.
Numbers · How much is left a year after stopping
Cost one: regain after stopping (the biggest problem)The STEP 1 extension (Wilding 2022): STEP 1 participants stopped both the drug and the lifestyle intervention at week 68, and 327 of them were followed for another 52 weeks; all of these analyses were exploratoryResult: within a year of stopping, about 2/3 of the lost weight came back. The drug group had lost 17.3%, then regained 11.6 percentage points, leaving a net loss of only 5.6%Metabolic markers (blood pressure, blood lipids, HbA1c, C-reactive protein ) mostly drifted back close to baselineMechanism: after weight loss, the signals that make you feel full (leptin, and PYY from the gut) run low and ghrelin, which makes you feel hungry, runs high; in Sumithran 2011, people who lost weight by diet had still not returned to their pre-diet levels after a year. The brain still believes it should return to the old weight, and once the drug stops, the hunger signals come backClinical meaning: drugs are long-term, possibly lifelong treatment, not a course you stop once the weight is off
Safety · The gut side effects
Cost two: gut side effectsThese are the most common side effects: many people on the drug report gut symptoms, but many on placebo do too, so what the drug adds is the difference between the two groupsIn STEP 1, nausea and diarrhea were the most common, followed by vomiting, constipation and abdominal pain; most were mild to moderate and eased with timeMostly worst while the dose is being increased, then tolerance developsStopping because of gut side effects: 4.5% in the drug group in STEP 1, against 0.8% with placeboSevere nausea and vomiting carry risks: dehydration, electrolyte imbalance and kidney injury. If you are vomiting so much you cannot keep fluids down, or you are passing much less urine, seek medical care promptlyHow to ease them: increase the dose slowly (one step every 4 weeks), eat small frequent meals, avoid large high-fat or high-fiber meals, and do not eat a lot at once
Evidence · What comes off is not only fat
Cost three: what comes off is not only fatA sizable share of the weight lost is lean mass (muscle, organs, water and bone, not only muscle). Whether it takes off more than other ways of losing weight is not settledMechanism: suppresses appetite, and protein intake often falls with it; the speed of the weight loss is also thought to play a partPossible consequences: by the mechanism, losing more muscle could make older people more prone to sarcopenia, falls and fractures; that step has no long-term dataCountermeasures:Protein: the usual advice is to eat more of it than usual. The evidence behind it comes from other weight-loss settings, such as Longland 2016 (AJCN): 40 young men, 4 weeks, an energy deficit of about 40%, plus high-intensity training 6 days a week; the group eating 2.4 g of protein per kilogram gained 1.2 kg of lean mass and the 1.2 g group gained 0.1 kg. The authors call it a proof-of-principle trial, and it was not done in people taking GLP-1 drugsStrength training: at least 2 times a weekWhere available, monitor lean mass with dual-energy X-ray absorptiometry ()Without these two, a larger share of the weight you lose may be lean mass
Safety · Rare but serious adverse events
Cost four: rare but serious adverse eventsAcute pancreatitis: rare, but serious when it happens, and the drug must be stopped. If you develop severe, persistent upper abdominal pain (it may spread to the back) with vomiting while on the drug, stop it and get medical care immediatelyGallbladder problems: rapid weight loss lets bile stagnate, raising the risk of gallstones and gallbladder inflammationThyroid C cells (animal data): medullary thyroid cancer appeared in rats, which has not been confirmed in people. People with a personal or family history of medullary thyroid cancer, or with multiple endocrine neoplasia type 2 (MEN2), must not use itWorsening diabetic retinopathy: a very fast drop in blood glucose may worsen it in the short term (people with type 2 diabetes need an eye examination before starting)Aspiration risk under surgical anesthesia (from the slower gastric emptying described earlier)
Evidence · Long-term safety data are still short
Cost five: long-term safety data (beyond 5 years) are still thinSemaglutide launched in 2017 (for diabetes) and was approved for weight loss in 2021, so large-scale long-term data cover less than 8 yearsTirzepatide launched in 2022, and its long-term data are thinner stillStill unknown: how long-term loss of lean mass affects physical function in older people, psychological dependence, the long-term burden on the pancreas and gallbladder, and rare immune reactions in a few people
In practice · Adding up the money
Cost six: moneyIn the US, it costs over a thousand dollars a month without insurance; coverage varies widely, and for the weight-loss indication (Wegovy, Zepbound) most private insurers and the federal Medicare program do not cover itIn China, semaglutide's diabetes indication is covered by the national health insurance, while the weight-loss indication is paid out of pocket and also costs over a thousand yuan a monthUsed long-term, or for life, the cumulative cost is very largeBlack-market and counterfeit risk: compounded injections and unverified supply channels have already been linked to several reports of serious adverse events
This is not a free lunch. It is a potent tool that requires a long-term commitment and carries real risk. Given to the right person, the benefit is large; given to the wrong person, side effects and muscle loss can far outweigh it.
Chapter 5
Who should use it, and how
drugs are not a tool you inject because you want to be thinner, and not a monster that must never be used. They are more like a long-term management tool on the level of blood-pressure drugs: given to the right person, used the right way, and kept up for the long term.
You would not tell someone with mild hypertension to take blood-pressure pills for 3 months, then stop and wait for the condition to cure itself, and GLP-1 is the same: treating obesity is treating a chronic metabolic disease, not fixing an image problem.
The people it suits best are those for whom all four of these are true: their weight is already at the threshold for drug treatment; they have made a serious attempt at lifestyle change for at least six months and still not reached their goal; they accept, psychologically and financially, that this may be long-term or even lifelong treatment; and they are willing to pair it with a high-protein diet, strength training and regular follow-up.
You would not tell someone with mild hypertension to take blood-pressure pills for 3 months, then stop and wait for the condition to cure itself, and GLP-1 is the same: treating obesity is treating a chronic metabolic disease, not fixing an image problem.
The people it suits best are those for whom all four of these are true: their weight is already at the threshold for drug treatment; they have made a serious attempt at lifestyle change for at least six months and still not reached their goal; they accept, psychologically and financially, that this may be long-term or even lifelong treatment; and they are willing to pair it with a high-protein diet, strength training and regular follow-up.
Clinical · When it fits
People to consider it (all four conditions must hold together; meeting one is not enough):One: ≥ 30 (for Asian people, it can reasonably be lowered to ≥ 28), or BMI ≥ 27 plus at least 1 weight-related comorbidity: type 2 diabetes, obstructive sleep apnea (), cardiovascular disease, severe hypertension, severe dyslipidemiaTwo: has seriously tried lifestyle change for ≥ 6 months (diet, exercise and behavioral support) and still not reached the goal, rather than looking for a shortcutThree: accepts that this is long-term, possibly lifelong treatment, and can carry it both psychologically and financiallyFour: is willing to do their part: a high-protein diet, strength training (≥ 2 times a week), and regular medical follow-up (once every 3 months)
Safety · Who should not use it
Not suitable, or should avoid it:Healthy adults who only want to lose 5–10 kg for their appearance: the side-effect risk, long-term commitment and cost are badly out of proportion to the benefit. This group should rely first on lifestyle, strength training and changing the structure of their dietPeople unwilling to use it long-term: after stopping, about 2/3 of the lost weight comes back, which amounts to a year of drug costs and side effects for nothing, plus tens of thousands of yuan spentPregnancy, planning a pregnancy, breastfeeding: safety data in pregnancy are insufficient, and the current advice is to stop at least 2 months before a planned pregnancyPeople who have had pancreatitis before: the risks add upA personal or family history of medullary thyroid cancer, or multiple endocrine neoplasia type 2 (MEN2): must not use itSevere gastroparesis or gastroesophageal reflux disease (): slowing gastric emptying further worsens the symptomsA history of an eating disorder (anorexia nervosa, binge eating): acts directly on appetite, which is a psychological riskUnder 18: only liraglutide and semaglutide have limited data in adolescents aged 12 and over, and most guidelines require a strict assessment
In practice · How to use it right
How to use it right (practical principles):Increase the dose slowly: semaglutide starts at 0.25 mg and steps up through 0.5, 1.0, 1.7 and 2.4 mg, one step every 4 weeks. Do not skip steps to get a faster effect; side effects will get markedly worsePair it with lifestyle: high protein, strength training, vegetables and fruit, less alcohol, enough sleep. Every trial stacked these, and there are no data supporting losing weight while lying flatMonitor regularly: weight, blood pressure, (HbA1c), liver and kidney function, lean mass by dual-energy X-ray absorptiometry () where available, as well as mental state and a thyroid examination by touchDo not combine it with other weight-loss drugs (such as orlistat or phentermine, or a prescribed drug plus a counterfeit bought on your own)Use legitimate channels: only products approved by the US FDA, China's NMPA or the European EMA; stay away from copycat injections, so-called magic compound powders, and unverified products bought through overseas personal shoppers
Background · Related stories
Related stories:Weight Management: before losing weight, understand energy balance, metabolic adaptation and the behavioral pillarsLeptin Resistance & Body-Weight Set-Point: explains why weight comes back after stopping (the brain guarding the old weight)Bariatric Surgery: the rung above , with indications and costs to compare side by sideType 2 Diabetes & Prediabetes: the main use of GLP-1 drugs in type 2 diabetes, and how that indication relates to weight lossProtein During a Deficit: how to actually keep muscle while losing weight
This is a class of drugs that changed how obesity is treated. But changing the approach is not magic: given to the right person, the benefit is large; given to the wrong person, it becomes a slow drain.
References · 11
- Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., et al. (2021). Once-weekly semaglutide in adults with overweight or obesity (STEP-1). New England Journal of Medicine, 384(11), 989-1002. 1961 adults with BMI >= 30 (or >= 27 with a weight-related condition) and no diabetes, randomized 2:1 to semaglutide 2.4 mg weekly or placebo, plus lifestyle intervention, for 68 weeks. Mean body-weight change -14.9% vs -2.4% (difference -12.4 percentage points); >= 15% loss in 50.5% vs 4.9%; -15.3 kg vs -2.6 kg; discontinuation for gastrointestinal events 4.5% vs 0.8%. Funded by Novo Nordisk (abstract, PMID 33567185). 10.1056/NEJMoa2032183
- Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., & Stefanski, A. (2022). Tirzepatide once weekly for the treatment of obesity. The New England Journal of Medicine, 387(3), 205–216. 2539 adults with BMI >= 30, or >= 27 with a weight-related complication, people with diabetes excluded; randomized 1:1:1:1 to tirzepatide 5, 10 or 15 mg weekly or placebo for 72 weeks (20-week dose escalation). Mean weight change (treatment-regimen estimand) -15.0%, -19.5% and -20.9% vs -3.1%; >= 20% loss in 50% and 57% on 10 and 15 mg vs 3%. Adverse events led to discontinuation in 4.3%, 7.1% and 6.2% vs 2.6%. Funded by Eli Lilly (abstract, PMID 35658024). 10.1056/NEJMoa2206038
- General Office of the National Health Commission of China. (2024). Guideline for the diagnosis and treatment of obesity (2024 edition). Issued 2024-10. China's first national clinical obesity guideline. Classification for Chinese adults: BMI 24 up to 28 is overweight and 28 or above is obesity, subdivided as mild 28.0 up to 32.5, moderate 32.5 up to 37.5, severe 37.5 up to 50. Central obesity: waist circumference is normal below 85 cm in men and 80 cm in women, and central obesity is diagnosed at 90 cm or more in men and 85 cm or more in women; a waist-hip ratio of 0.90 or more in men and 0.85 or more in women also establishes it. Weight-loss target: for most overweight and mildly obese patients, at least 5 to 15 percent of body weight within 3 to 6 months, then maintained, with reassessment every 3 to 6 months. Pharmacotherapy is indicated by clinical state rather than by a BMI number: overweight plus at least one weight-related comorbidity (hyperglycaemia, hypertension, dyslipidaemia, fatty liver, obstructive sleep apnoea, cardiovascular disease) where lifestyle intervention fails to reach the target, or obesity where lifestyle intervention fails to reach the target. Five drugs are approved in China for weight reduction in adult primary obesity: orlistat, liraglutide, beinaglutide, semaglutide and tirzepatide. Surgical indications: ages 18 to 70 with BMI 32.5 or above, or BMI 27.5 or above with type-2 diabetes regardless of whether medical treatment has succeeded; also ages 18 to 70 with BMI from 27.5 up to 32.5 where medical weight reduction has failed or an obesity-related disease is refractory to medical treatment. SCOPE NOTE: chapter 12 is traditional-Chinese-medicine treatment (syndrome differentiation, daoyin exercises), which is outside this site's content scope and is not cited anywhere. www.gov.cn/zhengce/zhengceku/202410/content_6981734.htm
- Sumithran, P., Prendergast, L. A., Delbridge, E., Purcell, K., Shulkes, A., Kriketos, A., & Proietto, J. (2011). Long-term persistence of hormonal adaptations to weight loss. The New England Journal of Medicine, 365(17), 1597–1604. 50 overweight or obese adults without diabetes on a 10-week very-low-energy diet; mean loss 13.5 kg. Measured at baseline, 10 and 62 weeks: leptin, ghrelin, PYY, GIP, GLP-1, amylin, pancreatic polypeptide, CCK, insulin and subjective appetite. At 62 weeks, leptin, PYY, CCK, insulin, ghrelin, GIP, pancreatic polypeptide and hunger still differed significantly from baseline; GLP-1 and amylin are not in that list. No thyroid hormone or energy-expenditure measure is reported in the abstract (abstract, PMID 22029981). 10.1056/NEJMoa1105816
- Blundell, J., Finlayson, G., Axelsen, M., Flint, A., Gibbons, C., Kvist, T., & Hjerpsted, J. B. (2017). Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes, Obesity and Metabolism, 19(9), 1242-1251. In 30 adults with obesity, 12 weeks of once-weekly semaglutide 1.0 mg reduced ad libitum energy intake by 24% (-3036 kJ) across the day vs placebo; resting metabolic rate adjusted for lean mass did not differ. 10.1111/dom.12932
- The Look AHEAD Research Group. (2013). Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. The New England Journal of Medicine, 369(2), 145–154. 5,145 overweight or obese adults with type 2 diabetes randomized to an intensive lifestyle intervention or diabetes support and education. Stopped early for futility at a median follow-up of 9.6 years. Weight loss 8.6% vs 0.7% at 1 year and 6.0% vs 3.5% at study end. Primary composite (cardiovascular death, nonfatal MI, nonfatal stroke, hospitalized angina): 403 vs 418 events, HR 0.95 (0.83-1.09), P = 0.51 - cardiovascular events were not reduced (abstract, PMID 23796131). 10.1056/NEJMoa1212914
- Eisenberg, D., Shikora, S. A., Aarts, E., Aminian, A., Angrisani, L., Cohen, R. V., De Luca, M., Faria, S. L., Goodpaster, K. P. S., Haddad, A., Himpens, J. M., Kow, L., Kurian, M., Loi, K., Mahawar, K., Nimeri, A., O'Kane, M., Papasavas, P. K., Ponce, J., … Kothari, S. N. (2022). 2022 American Society for Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO): Indications for metabolic and bariatric surgery. Surgery for Obesity and Related Diseases, 18(12), 1345–1356. Full text (conclusion): metabolic and bariatric surgery is recommended for BMI 35 or more regardless of co-morbidities, and for type 2 diabetes with BMI 30 or more; it should be considered at BMI 30-34.9 when nonsurgical methods do not achieve substantial or durable weight loss or co-morbidity improvement; in Asian populations obesity should be defined at a BMI threshold of 25-27.5, and clinical obesity is recognised above 25; there is no upper age limit (full text, SOARD, Wayback snapshot 2 July 2025). 10.1016/j.soard.2022.08.013
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