General principles
Pharmacotherapy should be considered as part of a comprehensive, long-term obesity-management programme that also includes nutritional therapy, physical activity, behavioural support and treatment of obesity-related complications. It is not a substitute for these interventions, but it can reduce hunger, improve satiation and make sustainable behavioural changes more achievable.
Anti-obesity medication may generally be considered for adults with:
Treatment decisions should not be based on BMI alone. The severity of obesity-related complications, previous treatment attempts, contraindications, patient preferences, expected benefits, treatment costs and the likelihood of long-term adherence should also be considered. Pharmacotherapy should be prescribed only within the authorised indication unless a carefully justified specialist decision is made. The German S3 guideline advises against prescribing glucose-lowering medicines off-label solely for weight reduction.
Obesity is a chronic, frequently relapsing condition. Pharmacological treatment may therefore need to be continued long term when it remains effective, safe and acceptable. Discontinuation of GLP-1-based treatment is commonly followed by increased appetite and partial or substantial weight regain. This reflects the underlying biology of obesity and should not be interpreted as treatment failure or lack of willpower. (PubMed)
Glucagon-like peptide-1 receptor agonists, abbreviated as GLP-1 receptor agonists or GLP-1 RAs, were originally developed for the treatment of type 2 diabetes. They:
Because insulin secretion is glucose dependent, GLP-1 receptor agonists have a low intrinsic risk of hypoglycaemia when used alone. The risk increases when they are combined with insulin or sulfonylureas.
Depending on the medicine, dose, baseline HbA1c and concomitant treatment, GLP-1 receptor agonists can reduce HbA1c by approximately 1–2 percentage points. Higher-dose semaglutide and tirzepatide may produce larger reductions in selected patients. The degree of weight loss varies substantially between agents and is generally smaller in people with type 2 diabetes than in people without diabetes.
Not all GLP-1 receptor agonists have the same evidence for cardiovascular benefit. In people with type 2 diabetes and established cardiovascular disease or a high cardiovascular risk, preference should be given to medicines with demonstrated cardiovascular benefit in the relevant population. Liraglutide, semaglutide and dulaglutide have shown cardiovascular benefits in specific outcome trials. In the SELECT trial, semaglutide 2.4 mg reduced major cardiovascular events by approximately 20% in adults with overweight or obesity and established cardiovascular disease but without diabetes. (PubMed)
The brand name and authorised indication are important. Preparations containing the same active substance are not necessarily interchangeable.
Medicine | Administration | Principal EU indication relevant to this section | Expected effect on weight |
Dulaglutide – Trulicity® | Once-weekly subcutaneous injection | Type 2 diabetes; not authorised specifically for obesity | Usually modest weight reduction |
Liraglutide – Victoza® | Once-daily subcutaneous injection | Type 2 diabetes | Modest weight reduction |
Liraglutide 3 mg – Saxenda® | Once-daily subcutaneous injection | Chronic weight management | Moderate average weight reduction |
Semaglutide – Ozempic® | Once-weekly subcutaneous injection | Type 2 diabetes; not authorised solely for obesity | Clinically relevant weight reduction, but obesity treatment with Ozempic constitutes off-label use |
Semaglutide 2.4 mg – Wegovy® | Once-weekly subcutaneous injection | Chronic weight management | Approximately 15% average weight reduction in STEP 1 |
Oral semaglutide – Rybelsus® | Once-daily tablet | Type 2 diabetes; not currently authorised as Rybelsus for obesity | Modest to clinically relevant weight reduction depending on dose and population |
Tirzepatide – Mounjaro® | Once-weekly subcutaneous injection | Type 2 diabetes and chronic weight management | Approximately 15–21% in SURMOUNT-1, depending on dose |
These values should not be interpreted as guaranteed individual outcomes. Study populations, treatment durations, background interventions and statistical methods differ, so indirect comparisons between trials must be made cautiously. (PubMed)
Dulaglutide is administered subcutaneously once weekly and is authorised for the treatment of type 2 diabetes, not specifically for obesity.
In the AWARD-11 trial, adults with type 2 diabetes treated with metformin received dulaglutide at doses of 1.5, 3.0 or 4.5 mg once weekly. At 36 weeks, the average reduction in body weight was approximately 3.0 kg with 1.5 mg and 4.6 kg with 4.5 mg. HbA1c decreased by approximately 1.5–1.8 percentage points. These results demonstrate a dose-dependent metabolic effect, but the weight reduction was substantially smaller than that generally observed with obesity-dose semaglutide or tirzepatide. (PubMed)
Liraglutide is administered once daily. Victoza® is authorised for type 2 diabetes, whereas Saxenda® at a target dose of 3 mg is authorised for chronic weight management.
In the STEP 8 head-to-head trial, adults with overweight or obesity without diabetes lost an average of 6.4% of their baseline body weight with liraglutide 3 mg, compared with 15.8% with semaglutide 2.4 mg. Liraglutide remains a possible treatment option when semaglutide or tirzepatide is unsuitable, unavailable or not tolerated. (PubMed)
Semaglutide is available in different formulations:
The formulations have different doses and indications and should not be substituted for one another without an appropriate prescription.
In the STEP 1 trial, adults with overweight or obesity without diabetes who received semaglutide 2.4 mg once weekly, together with lifestyle intervention, lost an average of approximately 14.9% of their baseline body weight after 68 weeks, compared with approximately 2.4% with placebo. Individual results varied considerably. (PubMed)
Cardiovascular outcome data
The SELECT trial included adults aged 45 years or older with overweight or obesity and established cardiovascular disease but without diabetes. Semaglutide 2.4 mg reduced the incidence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, with a hazard ratio of 0.80 compared with placebo. This evidence applies to the population studied and should not be generalised automatically to every person with obesity. (PubMed).
Oral semaglutide for type 2 diabetes
Rybelsus® contains oral semaglutide and is authorised in the EU for adults with inadequately controlled type 2 diabetes. It is not currently authorised under the Rybelsus name solely for obesity treatment.
Oral semaglutide has specific administration requirements because its absorption is easily reduced. The tablet should generally be:
The exact dosing instructions in the current product information must be followed. Different tablet formulations or strengths should not be assumed to be directly interchangeable.
Oral Wegovy
On 21 May 2026, the European Medicines Agency’s Committee for Medicinal Products for Human Use issued a positive opinion recommending the addition of oral Wegovy tablets in strengths of 1.5, 4, 9 and 25 mg. In the pivotal study assessed by the EMA, once-daily oral semaglutide 25 mg produced an average weight reduction of approximately 13.6% after 64 weeks, compared with approximately 2.2% with placebo)
A positive CHMP opinion is followed by the European Commission’s formal decision and implementation of the updated product information. Therefore, the final authorisation status, national availability and reimbursability of oral Wegovy should be confirmed before prescribing. Oral Wegovy and Rybelsus should not be treated as identical products merely because they both contain semaglutide.
Other oral GLP-1 receptor agonists
Orforglipron is an investigational, non-peptide oral GLP-1 receptor agonist. Phase 3 studies have demonstrated clinically relevant reductions in HbA1c and body weight. It was under regulatory evaluation in 2026 but had not yet become an established authorised treatment in the EU at the time of this revision. It should therefore not be included among routinely available treatment options until authorisation has been granted.)
Tirzepatide, marketed as Mounjaro®, is a once-weekly dual agonist of the glucose-dependent insulinotropic polypeptide receptor and the GLP-1 receptor. It improves glucose-dependent insulin secretion, reduces appetite and energy intake and produces substantial reductions in HbA1c and body weight.
In the EU, Mounjaro is authorised, together with diet and physical activity:
Relevant comorbidities may include hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease, prediabetes or type 2 diabetes.)
Dosage
The recommended starting dose is 2.5 mg once weekly. After four weeks, the dose is increased to 5 mg once weekly. When additional treatment benefit is required and the medicine is tolerated, the dose may be increased in increments of 2.5 mg after at least four weeks at the current dose.
Recommended maintenance doses are 5, 10 or 15 mg once weekly. The maximum dose is 15 mg once weekly. The 2.5 mg dose is intended for treatment initiation and is not normally a maintenance dose.
Effect on body weight
In the SURMOUNT-1 trial, adults with obesity or overweight and at least one weight-related complication, but without diabetes, achieved the following average weight reductions after 72 weeks:
The average baseline body weight was approximately 105 kg. The original statement that the 10 mg dose produced a 21.4% reduction should therefore be corrected. (PubMed)
In the direct SURMOUNT-5 comparison, tirzepatide produced a mean reduction of approximately 20.2%, compared with 13.7% with semaglutide 2.4 mg after 72 weeks. These are group averages and do not predict the result for an individual patient. (PubMed)
Tirzepatide has also demonstrated cardiovascular safety. In SURPASS-CVOT, it was non-inferior to dulaglutide for major cardiovascular events in people with type 2 diabetes and established atherosclerotic cardiovascular disease. This should not be phrased as proof that tirzepatide is superior to all GLP-1 receptor agonists for cardiovascular prevention. (PubMed)
Source: Jastreboff AM, et al.; SURMOUNT-1 Investigators. New England Journal of Medicine. 2022;387:205–216. (PubMed)
Gastrointestinal adverse effects
The most common adverse effects of GLP-1 receptor agonists and tirzepatide are:
These effects are usually most pronounced during dose escalation and often improve over time. Slow dose titration, smaller meals, avoiding very high-fat meals and stopping eating when comfortably full may improve tolerability. Dose escalation should be postponed when clinically relevant gastrointestinal symptoms persist.
Pancreatitis and pancreatic cancer
Acute pancreatitis is a recognised warning for GLP-1 receptor agonists and tirzepatide. Treatment should be discontinued and the patient assessed promptly when pancreatitis is suspected. Persistent, severe abdominal pain, particularly when radiating to the back or accompanied by vomiting, requires urgent medical evaluation.
Current evidence has not established that GLP-1 receptor agonists cause pancreatic cancer. However, it is too absolute to state that there is “no risk” or that the question has been definitively resolved. Pancreatic safety continues to be monitored through pharmacovigilance and long-term outcome studies.
Gallbladder disease
Rapid or substantial weight loss and GLP-1-based treatment can be associated with gallstones and cholecystitis. New upper abdominal pain, fever or jaundice should be investigated.
Hypoglycaemia
GLP-1 receptor agonists and tirzepatide have a low risk of hypoglycaemia when used without insulin or insulin secretagogues. When treatment is added to insulin or a sulfonylurea, the dose of these medicines may need to be reduced. Glucose monitoring should be intensified during treatment initiation and dose escalation.
Dehydration and kidney function
Vomiting or diarrhoea can cause dehydration and deterioration of kidney function. Patients should be advised to maintain adequate fluid intake and seek medical advice when gastrointestinal symptoms are persistent or severe. Renal function should be monitored when clinically indicated.
Diabetic retinopathy
Rapid improvement in glycaemic control can temporarily worsen diabetic retinopathy, particularly in patients with pre-existing retinopathy and high baseline HbA1c. Retinal assessment and appropriate ophthalmological follow-up should be considered before and during treatment in high-risk patients
Delayed gastric emptying and anaesthesia
GLP-1-based medicines delay gastric emptying and may increase the risk of retained gastric contents during general anaesthesia or deep sedation. Patients should inform the anaesthetist that they are using a GLP-1 receptor agonist or tirzepatide. Perioperative management should follow current anaesthetic and institutional guidance rather than an automatic discontinuation rule for every patient.
Pregnancy and breastfeeding
GLP-1 receptor agonists and tirzepatide should not be used for intentional weight loss during pregnancy. Effective contraception and pregnancy plans should be discussed before treatment.
Semaglutide should generally be discontinued at least two months before a planned pregnancy, whereas tirzepatide should generally be discontinued at least one month before a planned pregnancy, in accordance with the respective EU product information.
Thyroid cancer and MEN2
The statement that tirzepatide is formally contraindicated in every patient with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 reflects US labelling, but not the wording of the current EU Summary of Product Characteristics.
In the EU product information, the formal contraindication for Mounjaro is hypersensitivity to the active substance or an excipient. The European Medicines Agency concluded that the available evidence did not support a causal association between GLP-1 receptor agonists and thyroid cancer. Prescribers should nevertheless follow the current product information applicable in their country and assess unusual thyroid symptoms appropriately. (European Medicines Agency (EMA))
A very rare association between semaglutide and non-arteritic anterior ischaemic optic neuropathy has also been recognised by the EMA. Sudden loss or rapid deterioration of vision requires urgent ophthalmological assessment. (European Medicines Agency (EMA))
Baseline assessment and follow-up
Before treatment, the following should be documented where clinically relevant:
Follow-up should assess body weight, waist circumference, glycaemic control, adverse effects, treatment adherence, muscle strength, nutritional adequacy and achievement of individual health goals. Adequate protein intake and resistance exercise should be encouraged to limit loss of lean mass during substantial weight reduction.
GLP-1 medicines should not be combined with another GLP-1 receptor agonist. Different semaglutide products should likewise not be used simultaneously.
Other authorised pharmacological options include orlistat and naltrexone/bupropion. They generally produce less average weight loss than semaglutide 2.4 mg or tirzepatide, but may be appropriate for selected patients according to contraindications, treatment objectives, availability and cost.
Setmelanotide is reserved for certain rare, genetically confirmed disorders of the melanocortin pathway and is not a treatment for common polygenic obesity.
The selection of medication should be based on the patient’s obesity complications as well as the medicine’s expected effect, safety profile and contraindications. For example, naltrexone/bupropion is unsuitable in several conditions including uncontrolled hypertension, seizure disorders and current opioid treatment, while orlistat may cause gastrointestinal adverse effects and reduce the absorption of fat-soluble vitamins.
Marketing authorisation does not automatically establish reimbursement. Coverage depends on the prescribed indication, the national healthcare system or individual insurance plan, and any applicable prior-authorisation criteria. The information below reflects the position on 13 July 2026.
Region | Authorised product and indication | Coverage for type 2 diabetes | Coverage for obesity or weight management | Practical considerations |
European Union | In the EU, Mounjaro® is authorised for insufficiently controlled type 2 diabetes and for weight management in adults with obesity or overweight accompanied by at least one weight-related complication. | Reimbursement is determined separately by each member state. Coverage may be available when Mounjaro is prescribed for type 2 diabetes in accordance with national treatment and prescribing criteria. | There is no EU-wide reimbursement policy. France introduced national reimbursement for Mounjaro and Wegovy from 15 June 2026 under restricted, second-line criteria for severe obesity; statutory insurance covers 65%, with possible additional coverage depending on the patient’s circumstances. In Germany, statutory health insurance excludes Mounjaro when used for weight regulation, although it remains prescribable as a statutory benefit for type 2 diabetes. | The prescriber must verify the rules in the individual member state. Authorisation for weight management does not guarantee public reimbursement. National requirements may include previous nutritional treatment, a minimum BMI, obesity-related complications, specialist initiation and periodic assessment of treatment response.) |
United States | Tirzepatide is marketed as Mounjaro® for type 2 diabetes and as Zepbound® for chronic weight management. Zepbound is also authorised for moderate-to-severe obstructive sleep apnoea in adults with obesity. | Commercial insurance and Medicare Part D plans may cover Mounjaro for type 2 diabetes when it is included in the formulary. Prior authorisation, step therapy and proof of an FDA-approved indication may be required. | Commercial coverage of Zepbound remains plan-specific. Since 1 July 2026, eligible Medicare Part D beneficiaries can obtain the Zepbound KwikPen for weight management through the temporary Medicare GLP-1 Bridge, generally with a USD 50 monthly copayment after prior authorisation. The programme is scheduled to continue through 31 December 2027. | Mounjaro should not be submitted as an obesity medicine in the United States because the obesity-specific tirzepatide product is Zepbound. Medicare beneficiaries receiving tirzepatide for type 2 diabetes or another indication already coverable under Part D must use their ordinary Part D coverage rather than the Bridge programme. (U.S. Food and Drug Administration) |
India | Mounjaro is available by prescription in India. Tirzepatide received regulatory approval for type 2 diabetes, and the Indian regulator subsequently recommended permission for its chronic weight-management indication, subject to post-marketing requirements. | No routine nationwide outpatient reimbursement pathway for Mounjaro has been identified. Coverage under private insurance depends on the exact contract and the presence of an outpatient or pharmacy benefit. | Treatment is generally paid for directly by the patient. India’s principal publicly financed PM-JAY programme is primarily a hospital-based scheme and excludes routine outpatient care and outpatient medicines from its standard benefit package. | Patients should obtain written confirmation from their insurer before treatment. Ordinary hospitalisation policies should not be assumed to cover a long-term, self-administered outpatient medicine. This assessment is an inference from the structure of public and private coverage and should be checked against the patient’s current policy. |
Medicare GLP-1 Bridge eligibility in the United States
For weight-management treatment under the Medicare GLP-1 Bridge, the prescriber must submit a prior-authorisation request. The patient must generally have:
The programme covers the Zepbound KwikPen, not the Zepbound single-dose vial or single-dose pen. (cms.gov)
Under the German statutory health-insurance system, medicines used specifically for weight reduction or appetite regulation are excluded as “lifestyle medicines.” Annex II of the Federal Joint Committee’s Pharmaceutical Directive explicitly includes Mounjaro when used for weight regulation, as well as Wegovy and Saxenda. This exclusion applies even though these medicines have an authorised obesity indication. (Gemeinsamer Bundesausschuss)
Mounjaro can nevertheless be prescribed at the expense of statutory insurance for its authorised type 2 diabetes indication when the clinical and prescribing requirements are met. The simultaneous presence of obesity does not invalidate reimbursement when the medicine is genuinely being used to treat diabetes, but clear documentation is important. (Gemeinsamer Bundesausschuss)
Private insurers generally assess reimbursement according to the individual policy, medical necessity and the agreed tariff. Prior authorisation is particularly advisable when Mounjaro is prescribed solely for obesity. (PKV)
The original heading should not describe this graph as a percentage change if the vertical axis reports kilograms. Dulaglutide was investigated as diabetes treatment in AWARD-11 and should not be presented as an obesity-specific treatment.