The New Weight-Loss Injections: What They Do and What They Do Not
Few medicines have generated as much attention as the GLP-1 based weight-loss drugs. They work, which is genuinely new, and almost everything else about how they are discussed is distorted in one direction or the other.
How they work
GLP-1 is a hormone released by the gut after eating. It stimulates insulin release when glucose is high, suppresses glucagon, slows stomach emptying and acts on appetite centres in the brain.
The drugs are long-acting analogues of this hormone. Semaglutide acts on GLP-1 receptors; tirzepatide acts on both GLP-1 and GIP receptors and produces greater weight loss.
The dominant effect for weight is on appetite. People describe reduced hunger, earlier fullness, and a marked reduction in persistent food-related thoughts, sometimes called food noise. They eat less because they want less, which is why these drugs succeed where willpower-based approaches usually fail.
Effectiveness
In the major trials, average weight loss over about 68 to 72 weeks was roughly 15 percent of body weight with semaglutide and around 20 percent with tirzepatide at higher doses, compared with a few percent on placebo. These are averages; individual response varies widely, and a minority respond poorly.
For context, that approaches the range previously achievable only with surgery.
Beyond weight, trials have shown reduced cardiovascular events in people with obesity and established heart disease, improvement in sleep apnoea, in knee osteoarthritis pain, in fatty liver disease, and in kidney outcomes in diabetic kidney disease. These matter as much as the weight number.
Side effects
Common, mostly gastrointestinal and worst during dose escalation: nausea, vomiting, diarrhoea, constipation, reflux, burping, abdominal pain, reduced appetite, fatigue. Most improve with slower titration and smaller, lower-fat meals.
Less common but important:
- Pancreatitis: severe persistent abdominal pain radiating to the back, with vomiting, needs immediate assessment
- Gallstones, more likely with rapid weight loss
- Gastroparesis, markedly delayed stomach emptying
- Dehydration and kidney injury from persistent vomiting
- Worsening of diabetic retinopathy with rapid glucose improvement
- Hypoglycaemia when combined with insulin or sulfonylureas, requiring those doses to be reduced
- Muscle loss: a substantial proportion of weight lost is lean mass unless protein intake and resistance training are maintained. This is the most under-discussed harm
- Anaesthetic risk from retained stomach contents; tell your anaesthetist well before any procedure
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Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN2, in pregnancy and breastfeeding, and with previous pancreatitis as a caution.
What happens when you stop
This is the part the marketing omits. In the withdrawal trials, participants regained roughly two thirds of the lost weight within a year of stopping, and cardiometabolic improvements reversed with it.
Obesity behaves like a chronic condition, and these drugs treat it the way antihypertensives treat blood pressure: while taken. For most people the realistic framing is long-term treatment, not a course.
That raises a cost question that is unavoidable, since these drugs are expensive and generally not covered by insurance for weight alone in India.
Who they are for
Generally considered for a BMI of 30 or above, or 27 or above with a weight-related condition such as type 2 diabetes, hypertension, sleep apnoea, fatty liver or osteoarthritis. Asian-specific thresholds are lower, typically 27.5 and 25 respectively.
They are not for cosmetic weight loss in people of normal weight, and the current shortages caused by that use have affected people with diabetes who need them.
Using them properly
A prescription is the smallest part of it:
- Protein intake of roughly 1.2 to 1.6 g per kg body weight, which is difficult on a markedly reduced appetite and must be planned deliberately
- Resistance training two to three times a week to preserve muscle
- Gradual dose escalation to limit side effects
- Smaller, slower meals; stopping at the first sense of fullness
- Adequate fluids and fibre
- Monitoring of weight, blood pressure, glucose and ideally body composition
- Review of other medications, particularly insulin and sulfonylureas
- Attention to the behavioural and psychological side, which does not disappear because appetite is suppressed
Warnings about sourcing
Compounded, unlicensed and online-sourced versions have caused serious harm, including dosing errors from unfamiliar syringes and products containing the wrong salt form or nothing active at all. Buy only a licensed product through a legitimate prescription and pharmacy.
What has not changed
These drugs do not replace diet quality, physical activity, sleep and treatment of the conditions that accompany obesity. They make the behavioural changes achievable for people for whom hunger had made them impossible, which is a real and significant thing, but the changes still have to happen.
Nor do they make obesity a character question answered. Obesity is driven by biology, environment and genetics far more than by discipline, and a drug that reduces hunger is evidence for that rather than against it.
This is general information, not a recommendation. These are prescription medicines with real contraindications and side effects; whether they suit you is a decision for a doctor who knows your history.