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Summary of recommendations

Management algorithm

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Evidence Review and Environmental Scan

Appendices

Executive summary and recommendations

Obesity and cardiovascular disease

A clinical consensus statement from the National Heart Foundation of Australia

Overview
Pharmacotherapy
Surgical interventions

Section 3: Pharmacological and surgical interventions

Pharmacological and surgical interventions play a critical role in the management of overweight and obesity, particularly among those at high cardiovascular risk or with established CVD.^186,187

Pharmacotherapy is indicated for obesity management, in conjunction with behaviour modifications, when adequate weight-related health improvements cannot be attained through behaviour modifications alone. Weight loss of approximately 5–10% of total body weight is generally required to attain these weight-related health improvements.^188,189 Pharmacotherapy should complement, not replace, behaviour modifications.^106,190,191

Incretin-based medicines (including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists) have changed the landscape of obesity management. High quality trials have demonstrated incretin-based medicines improve cardiometabolic risk factors and, in some cohorts, reduce the risk of major adverse cardiovascular events.^11,12 Across trials, they have consistently led to substantial weight loss, achieving reductions exceeding 10% of baseline body weight.^{11,190,192,193} To note, real world observational data suggest that average weight loss is lower than that seen in randomised controlled trials due to a combination of lower achieved dosages, treatment interruptions and high discontinuation rates (up to 20–50% within the first year).^194,195

General practitioners are well-placed to support people in commencing obesity management medications and to support ongoing care. Weight regain is common after ceasing these agents, therefore they are likely to be needed long term.¹⁹⁶

For people who are unable to attain weight-related health improvements with behaviour modifications and pharmacotherapy, or unable to sustain weight loss after treatment discontinuation, referral to specialised care is generally required. This may include consideration of metabolic bariatric surgery to achieve weight goals and improve cardiovascular health.

Multiple systematic reviews and meta-analyses, of predominantly cohort studies, have shown that metabolic bariatric surgery is consistently associated with reduced cardiovascular morbidity and mortality among individuals with obesity (predominantly in people at high risk of CVD with some lower quality evidence demonstrating benefit in people with established disease).^187,197-202

Procedures such as sleeve gastrectomy and Roux-en-Y gastric bypass not only achieve sustained weight loss, but can also induce remission of type 2 diabetes, lower blood pressure, improve lipid profiles, and may reduce the risk of heart failure exacerbations.^203-206 Metabolic bariatric surgery has also been associated with short term improvements in mental health, depressive symptoms and quality of life, but longer‑term mental health outcomes are heterogeneous.^207-209

Access and cost remain significant barriers for obesity management medications and metabolic bariatric surgery. There are currently no Therapeutic Goods Administration-approved incretin-based medicines available on the Pharmaceutical Benefits Scheme (PBS) for obesity management (Table 7). This means the cost remains prohibitive for many people.²¹⁰At the time of writing, the Pharmaceutical Benefits Advisory Committee has made a positive recommendation for semaglutide in a subgroup of people with obesity and established CVD.²¹¹

Similarly, metabolic bariatric surgery has limited availability in the vast majority of Australian public hospitals, with more than 90% of procedures taking place in the private sector.²¹²Financial barriers are likely to compound inequities given the disproportionate burden of obesity and CVD in priority populations who may have limited access to private medical and surgical care.²¹⁰With a growing prevalence of obesity and overweight in Australia, expediting mechanisms to improve access to multidisciplinary obesity care is critical.

Pharmacotherapy

Recommendations	Strength of advice
Obesity management medications are indicated, in conjunction with behaviour modifications, when adequate weight-related health improvements cannot be attained through behaviour modifications alone.	Strong advice
In adults living with established atherosclerotic CVD and BMI ≥ 27 kg/m², consider prescribing a GLP-1 receptor agonist with proven CVD benefit (semaglutide) to reduce the risk of major adverse cardiovascular events.	Moderate advice
In adults living with heart failure with preserved ejection fraction (HFpEF) and obesity^α, consider semaglutide or tirzepatide to improve symptoms and functional capacity.	Moderate advice
In adults living with type 2 diabetes and overweight or obesity, with or without CVD, consider a GLP-1 or GIP/GLP-1 receptor agonist with proven CVD benefit (semaglutide, liraglutide or tirzepatide) to reduce the risk of major adverse cardiovascular events.	Strong advice
^αDefined in trials as BMI ≥ 30 kg/m² and ejection fraction ≥ 50% (SUMMIT, tirzepatide) or ejection fraction ≥ 45% (STEP-HFpEF, semaglutide). While these medications have demonstrated benefit for heart failure symptoms and quality of life, they are not yet approved by the Therapeutic Goods Administration for management of this condition.

General information

Obesity management medications approved for use in Australia by the Therapeutic Goods Administration (TGA) are listed in Table 8.

The injectable GLP-1 receptor agonists (e.g. semaglutide, liraglutide) and GIP/GLP-1 receptor agonists (tirzepatide) promote weight loss via several different mechanisms of action (Figure 5). Cardiovascular outcome trials of these agents have also demonstrated improvement in cardiometabolic markers including blood pressure and lipid profiles.^190,213

GLP-1 receptor agonists act by binding to and amplifying activation of the GLP-1 receptor, resulting in enhanced post-prandial insulin secretion, glucagon release inhibition, delayed gastric emptying and appetite suppression.²¹⁴

The cardioprotective effects of semaglutide may be independent of its impact on weight, suggesting additional underlying mechanisms, including anti-inflammatory effects such as reductions in systemic inflammatory markers, which may contribute to cardiovascular benefit.^215,216

The GIP/GLP-1 receptor agonists have an additional agonism effect at the GIP receptor, resulting in increased insulin secretion in a glucose dependent manner and combined effects on appetite regulation and weight loss.^217,218

Table 8: Therapeutic Goods Administration-approved obesity management medications, their indications and relevant PBS criteria

Medication name	TGA indications	PBS criteria (for obesity management)
Incretin-based agents
Semaglutide	Management of weight in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of one or more weight-related complications.	Not included on PBS*
Tirzepatide	Management of weight in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of one or more weight-related complications.	Not included on PBS
Liraglutide	Management of weight in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of one or more weight-related complications.	Not included on PBS
Oral agents
Orlistat	Management of weight in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of one or more weight-related complications.	Included on Repatriation Pharmaceutical Benefits Scheme, for individuals with BMI ≥ 35 kg/m² with no known co-morbidities or BMI ≥ 30 kg/m² with at least one co-morbidity.
Naltrexone/bupropion	Management of weight in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of one or more weight-related complications.	Not included on PBS
Phentermine	Management of weight in adults with a BMI ≥ 25 kg/m².	Not included on PBS

* At the time of writing, the Pharmaceutical Benefits Advisory Committee has made a positive recommendation for semaglutide in a subgroup of people with obesity and established CVD.

Figure 5: Mechanisms of action of GLP-1 receptor agonists and GIP/GLP-1 receptor agonists.^190,219-222

^{*Further research is required to fully understand the cardioprotective mechanisms of these agents.}

^{Abbreviations: GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; HbA1c, haemoglobin A1c.}

Compared with injectable pharmacotherapies, the oral agents orlistat, naltrexone/bupropion and phentermine are less effective for weight loss and lack CVD outcome data (Table 9).

For phentermine, there are several CVD-related contraindications (e.g. valvular disease, arrhythmias and advanced arteriosclerosis) and precautions (e.g. mild hypertension). Similarly, naltrexone/bupropion is contraindicated in people with uncontrolled hypertension and is cautioned in people with controlled hypertension.^223-225 Refer to individual agent product information for more detail.

Table 9: Pharmacotherapies for obesity management^{219,223,224,226-243}

Table 9: Pharmacotherapies for obesity management - Incretin based agents

Table 9: Pharmacotherapies for obesity management - Oral agents

Figure 6:Efficacy of weight management interventions for weight loss.^{*83,228,236-238,245-249}

^{*To note, the efficacy for weight loss percentages represents findings from several studies of varying cohorts and study quality. They do not represent head-to-head comparison studies and are intended to provide a general indication of comparative efficacy. Figures for semaglutide and tirzepatide have been derived from published cardiovascular outcome trials. In the case of liraglutide, the SCALE trial was used as the reference for percentage total body weight lost, in preference to the LEADER cardiovascular outcome trial. The latter used approximately half the maintenance dose of liraglutide that is indicated for weight management. For each intervention, the bar represents the upper end of the range for approximate percentage of total body weight loss.}

Practice points

Initiation and titration

Pharmacotherapy may be considered when weight-related health improvements, such as improvements in lipids, blood glucose levels, blood pressure and metabolic dysfunction-associated steatotic liver disease, have not been attained with behaviour modifications alone, or the weight loss required is higher than what can be achieved through behaviour modifications.
Pharmacotherapy for obesity management should be initiated as part of a comprehensive management plan, which includes the continuation of behaviour modifications (nutrition and physical activity).
In certain cases, especially among individuals with a higher BMI and existing complications, initiation of pharmacotherapy may be warranted as a first-line intervention along with behaviour modifications. Shared decision-making is critical at that stage, factoring in the person’s preferences and values. The high cost of obesity management medications, particularly incretin-based agents, means they remain inaccessible for many people.
The starting dose of semaglutide is 0.25 mg subcutaneous once weekly, which can be increased incrementally every four weeks to a maintenance dose of 2.4 mg:²⁵⁰

weeks 1–4: 0.25 mg
weeks 5–8: 0.5 mg
weeks 9–12: 1 mg
weeks 13–16: 1.7 mg
maintenance dose: 2.4 mg.

Slow initiation helps to minimise gastrointestinal side effects.

To note, Wegovy (semaglutide) is a higher dose semaglutide formulation which has been approved by the TGA for chronic weight management at a maximum dose of 2.4 mg weekly. Ozempic is only TGA-approved for type 2 diabetes. Oral formulations of semaglutide exist (one is TGA-approved for diabetes) but are not commercially available in Australia at the time of writing. A higher dose injectable semaglutide formulation (7.2 mg) is currently pending TGA approval.²⁵¹

The starting dose of tirzepatide is 2.5 mg subcutaneous once weekly. After four weeks, the dose can be increased to 5 mg weekly. Dose can be further increased by 2.5 mg every four weeks to a maximum dose of 15 mg once weekly as required.²⁵²

The starting dose of liraglutide is 0.6 mg subcutaneous once daily. Doses should be increased in 0.6 mg increments at intervals of at least one week to a maintenance dose of 3 mg daily.^219,234
Oral agents (e.g. orlistat, naltrexone/bupropion and phentermine) have a limited role in the management of overweight/obesity in people with or at high risk of CVD due to their minimal impact on weight, unknown CVD benefits and poor tolerability.
After commencement of pharmacotherapy, regularl assessment of weight, cardiometabolic risk factors and treatment tolerability should be undertaken. The dose of pharmacotherapy should be adjusted if required to achieve health targets (increasing or decreasing the dose). Monitor for nutritional adequacy if clinical concerns such as poor diet quality, disordered eating behaviour or very rapid weight loss occur (typically > 1.5–2 kg per week). See section on ‘Dietary advice for people on incretin-based medications’. Engage multidisciplinary team, including pharmacists and allied healthcare professionals, to support adherence.
Advise people that ongoing pharmacotherapy, in conjunction with behaviour modifications, is likely to be needed to maintain a healthy weight and effectively manage CVD risk in the long term. Weight regain is common after cessation of pharmacotherapy. Some studies show up to 60% of weight lost during treatment is regained one-year post cessation,¹⁹⁶ and cardiometabolic risk factor improvements may be reversed (e.g. HbA1c, cholesterol and blood pressure).²⁵³

Side effects

Advise people that the most common side effects of incretin-based obesity management medications are gastrointestinal and can include nausea, diarrhoea, constipation and vomiting. These side effects have been reported in approximately 20–40% of people and are most common during dose initiation and escalation.^250,252 In most people, these side effects can be mitigated by commencing at a lower dose and titrating the dose gradually over weeks.
People should be advised that having smaller, more frequent meals and avoiding fatty foods can alleviate nausea and vomiting side effects during treatment initiation.254 Adequate fluid and fibre intake can also help alleviate the side effect of constipation.254
The use of GLP-1 receptor agonists has been associated with rarer side effects including an increased risk of acute pancreatitis, gastroparesis and intestinal obstruction although incidence is rare (<0.1%).²¹⁹ Inform people about the symptoms of pancreatitis and when to seek medical attention.²⁵⁰If pancreatitis occurs, the GLP-1 receptor agonist should not be restarted. Similarly, exercise caution when commencing these medications in people with a history of acute pancreatitis.
A newly identified safety signal, based on a small number of case reports, indicates a possible association between GLP-1 receptor agonists (including tirzepatide) and suicidal ideation.^255,256 Whilst international regulators (e.g. US Food and Drug Administration) have now removed such warnings, the Therapeutic Goods Administration has updated product safety warnings and advised healthcare professionals to monitor people for changes in mood, behaviour or emerging suicidal thoughts or behaviours.
Case reports have linked GLP-1 receptor agonists and GLP-1/GIP receptor agonists to an increased potential risk of regurgitation and pulmonary aspiration during anaesthesia due to delayed gastric emptying.²⁵⁷ Preprocedural clinical consensus advice should be followed (see Resources and further reading).
Advise people that most over-the-counter and online weight loss products, including complementary and herbal supplements, have limited or no evidence for their safety and efficacy. Counterfeit medications disguised as weight loss products are not uncommon. These agents are illegal and can contain harmful, undisclosed ingredients, including sibutramine which has been shown to increase the risk of heart attack and stroke.²⁵⁸

Lean muscle mass loss

Sarcopenia (loss of muscle strength, mass and function) can be exacerbated by chronic comorbidities, including CVD, and is associated with faster disease progression and higher mortality in these groups.²⁵⁹
Maintenance of lean mass is important during weight loss because muscle mass facilitates a higher metabolic rate and makes it easier to lose and maintain body weight after a weight loss intervention.
While dietary weight loss strategies typically cause some loss of lean muscle, GLP-1 and GIP/GLP-1 receptor agonists are associated with significant loss of lean mass ranging from 15–45% of total weight loss,260 varying by agent.
Strategies to mitigate lean muscle loss while on treatment include optimising dietary protein, recognising that GLP-1 and GIP/GLP-1 receptor agonists may suppress appetite and substantially reduce overall energy intake, increasing the risk of inadequate protein consumption.260-262
Regular resistance exercise training can help preserve lean muscle mass during weight loss and should be performed on two or more days per week, where clinically appropriate.159

Dietary advice for people on incretin-based medications

Incretin-based medications increase the risk of muscle loss, sarcopenic obesity and nutrient deficiencies.²⁶³Prescribers of obesity management medications should consider concurrent referral to an Accredited Practising Dietitian to optimise outcomes.²⁶³
People on incretin-based medications should prioritise adequate protein intake (1.2–1.60 g/kg of body weight per day, or an absolute target of 80–120 g/day where appropriate),²⁵⁴combined with structured resistance exercise, to support preservation of lean mass during weight loss. Increased protein intake alone is unlikely to preserve muscle mass in the absence of resistance training.
Supplementation may assist in meeting protein and micronutrient requirements when dietary intake is insufficient.²⁶³
Reduced appetite with GLP‑1 receptor agonists may result in unintentional intermittent fasting. Individuals should be encouraged to consume meals at regular intervals, as prolonged fasting without adequate protein intake or dietary variety may increase the risk of nutritional inadequacy.²⁵⁴
More aggressive caloric restriction strategies including LEDs and VLEDs are generally not appropriate in combination with incretin-based medications unless under close specialist supervision with monitoring of body composition and nutritional status.

Considerations in people with type 2 diabetes

In adults living with type 2 diabetes and overweight or obesity, consider prescription of glucose-lowering agents with dual weight management and cardiovascular benefits to reduce the risk of major adverse cardiovascular events.
GLP-1 receptor agonists with demonstrated cardiovascular benefit in people with type 2 diabetes include liraglutide,²²⁷semaglutide,²²⁹and dulaglutide.²⁶⁴
Tirzepatide, a GIP/GLP-1 receptor agonist, has also demonstrated cardiovascular benefit in people with type 2 diabetes.²⁴⁵
At the time of writing, semaglutide and dulaglutide can only be prescribed on the PBS for type 2 diabetes specifically, not obesity management.
SGLT-2 inhibitors (such as empagliflozin and dapagliflozin) are also indicated for the treatment of type 2 diabetes and have been shown to have modest weight-lowering effects in this population.²⁶⁵These drugs offer significant cardiovascular and renal benefits.266
Healthcare professionals should be aware of potential drug interactions with the use of GLP-1 receptor agonists and GIP/GLP-1 receptor agonists in combination with other glucose-lowering agents (e.g. sulfonylureas, insulin) due to an increased risk of hypoglycaemia.^250,252 Monitor and consider titrating the dose of sulfonylurea or insulin when commencing a GLP-1 receptor agonist or GIP/GLP-1 receptor agonist.²⁶⁷
In people with type 2 diabetes, assess for retinopathy during GLP-1 receptor agonist initiation and titration, due to the increased risk of retinopathy associated with a rapid reduction in glycosylated haemoglobin (HbA1c).²⁶⁸
Emerging safety signals suggest a possible rare association between GLP-1 receptor agonists (particularly semaglutide) and GIP/GLP-1 receptor agonists, and non-arteritic anterior ischemic optic neuropathy in people with type 2 diabetes, however further research is warranted.^269-271

Considerations in older people

Evidence for the safety and efficacy of obesity management medications in older people is limited. Healthcare professionals should consider the increased risk of sarcopenia and nutrient deficiencies when prescribing these medications and reinforce appropriate nutrition and resistance training.^263,272

Considerations in women

Women of reproductive age taking a GLP-1 receptor agonist or tirzepatide should be advised to use contraception concurrently due to potential safety concerns associated with taking these pharmacotherapies in pregnancy (as shown in animal studies).^273,274 Semaglutide and tirzepatide are both classified as pregnancy category D medications.^250,252
Tirzepatide and GLP-1 receptor agonists may decrease absorption of oral contraceptives due to delayed gastric emptying, however the evidence is inconsistent.275 As a precaution to avoid unplanned pregnancy, current product information for tirzepatide includes advice that women should switch to a non-oral contraceptive or add a barrier method of contraception for four weeks after initiation, and for four weeks after each dose escalation.²⁷⁶This advice has not been extended to GLP-1 receptor agonists (liraglutide and semaglutide) at the time of writing.

Considerations in people with heart failure

When initiating and escalating semaglutide or tirzepatide in people with obesity and heart failure with preserved ejection fraction (HFpEF), monitor kidney function and electrolytes and adjust other medications (e.g. diuretics, antihypertensives, glucose-lowering agents) if required, particularly if the person is experiencing gastrointestinal side effects.²⁷⁷
Semaglutide and tirzepatide have been shown to improve quality of life and functional capacity in people with HFpEF and BMI ≥ 30 kg/m2, but insufficient evidence exists to conclude cardiovascular outcome benefits.^278,279
There is a lack of high-quality trial data evaluating the cardiovascular impact of GLP-1 receptor agonists in people with heart failure with reduced ejection fraction.
SGLT-2 inhibitors are also indicated for the management of both reduced and preserved ejection fraction heart failure and may have modest weight-lowering effects in these populations.²⁸⁰ These medications include empagliflozin and dapagliflozin, which are included on the PBS for the indication of chronic heart failure.

Considerations in people with other comorbidities

Tirzepatide is also indicated for the treatment of moderate-to-severe obstructive sleep apnoea in adults with obesity.²⁵²
GLP-1 receptor agonists have emerged as an important treatment option for diabetic kidney disease in the context of type 2 diabetes, with semaglutide showing reduced risk of clinically important kidney outcomes and death from cardiovascular causes in people with type 2 diabetes and chronic kidney disease.²⁸¹
Incretin-based therapies are emerging as a treatment for metabolic dysfunction-associated liver disease (formerly non-alcoholic fatty liver disease), with evidence suggesting benefits in liver histology and a reduction in liver fat.^282,283 The Therapeutic Goods Administration has recently provisionally approved semaglutide for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) in adults with moderate to advanced liver fibrosis.^231,284

Summary of the evidence

Evidence for the use of incretin-based therapies in a CVD primary prevention cohort largely draws from trials involving people with type 2 diabetes. The LEADER, SUSTAIN-6, and REWIND trials collectively demonstrate the cardiovascular outcome benefits of GLP-1 receptor agonists in people with type 2 diabetes and at high CVD risk.

LEADER (9,340 participants, median 3.8 years) showed liraglutide reduced major adverse cardiovascular events compared with placebo (HR 0.87; 95% CI 0.78–0.97).²²⁷
SUSTAIN-6 (3,297 participants, median two years) found semaglutide provided an even greater relative risk reduction compared with placebo (HR 0.74; 95% CI 0.58–0.95).²²⁹
REWIND (around 9,900 participants, approximately one third with established CVD, median 5.4 years) demonstrated dulaglutide lowered major adverse cardiovascular event risk compared with placebo (HR 0.88; 95% CI 0.79–0.99).²⁶⁴

The cardiovascular outcome trial for tirzepatide (SURPASS-CVOT) has demonstrated cardiovascular benefit in people with type 2 diabetes and atherosclerotic CVD.^229,245,285 In SUPRASS-CVOT, tirzepatide was found to be non-inferior to dulaglutide (HR 0.92; 95% CI 0.83-1.01).²⁴⁵ At the time of writing, the SURMOUNT-MMO trial is currently underway to investigate the cardiovascular outcomes of tirzepatide in people with overweight/obesity without type 2 diabetes.²⁸⁶
The landmark SELECT trial has demonstrated the cardiovascular benefits of the GLP-1 receptor agonist, semaglutide (2.4 mg subcutaneous once weekly), in people established atherosclerotic CVD and with a BMI ≥ 27 kg/m2 (without type 2 diabetes). In this double-blind, placebo-controlled randomised clinical trial of 17,604 adults, semaglutide reduced the incidence of cardiovascular death, myocardial infarction and stroke (HR 0.80; 95% CI 0.72–0.90).²²⁸
There is growing evidence to support the role of GLP-1 receptor agonists and GIP/GLP-1 receptor agonists in improving heart failure-related symptoms and quality of life in people with HFpEF in the setting of obesity,^278,279 and in concurrent obesity and type 2 diabetes.²⁸⁷ In the SUMMIT trial, tirzepatide showed a significant reduction in heart failure events in people with HFpEF but results should be interpreted with caution due to small event numbers.²⁷⁹
Emerging unpublished observational data suggest that GLP-1 receptor agonists may also play a secondary prevention role in people with atrial fibrillation, obesity and type 2 diabetes, although further research is underway.²⁸⁸

Resources and further reading

Australian Register of Therapeutic Goods Product Information
Pharmaceutical Benefits Scheme
Australian Diabetes Society. Clinical practice recommendations: Periprocedural use of GLP-1 RAs and GLP-1/GIP RAs

Emerging pharmacotherapies

Several novel obesity management medications and formulations are currently being investigated in clinical trials. Some selected new therapies on the horizon are discussed below.

Retatrutide, a triple agonist against GLP-1, GIP and glucagon receptors, has demonstrated significant weight loss (up to a 24% reduction in body weight at the highest dose) and metabolic benefits in people with obesity, both with and without type 2 diabetes in phase 2 clinical trials.^289,290
Survodutide is a novel dual glucagon receptor and GLP-1 receptor agonist.291 In phase 2 trials, it conferred significant weight loss (up to 19% of total body weight) in people with obesity without type 2 diabetes.²⁹² Phase 3 clinical trials are currently underway in both people with and without type 2 diabetes, in addition to a cardiovascular outcomes trial.²⁹³
Oral semaglutide (25 mg) daily achieved 11.4% reduction in body weight compared with placebo (95% CI -13.9-9.0) in people with overweight and obesity.²⁹⁴ While not a head-to-head study, this is comparable to observed body weight reduction achieved with subcutaneous semaglutide 2.4 mg weekly. Trials have demonstrated that oral semaglutide reduces the risk of major adverse cardiovascular events (HR 0.86; 95% CI 0.77 to 0.96) in people with type 2 diabetes and established CVD and/or chronic kidney disease, without an increase in risk of serious adverse events.²⁹⁵
A novel oral GLP-1 receptor agonist – orforglipron– has shown significant glycaemic and weight loss benefits in people with and without type 2 diabetes.^296-298
CagriSema, a combination of cagrilinitide and semaglutide, is a dual GLP-1 receptor agonist and long-acting amylin analogue. The REDEFINE trials have shown that CagriSema confers clinically significant weight loss (approximately 20% of total body weight) compared with placebo, in both people with and without type 2 diabetes.^299,300
Phase 2 trials of once weekly administration of the amylin receptor agonist, eloralintide, in adults with overweight or obesity and without type 2 diabetes have demonstrated significant weight loss, with a mean decrease in body weight ranging from 9–16%, compared with 0.4% in the placebo group.301 Combination therapy of amylin and semaglutide has also shown promise in weight management, with over 40% of trial participants achieving a decrease in body weight of ≥ 25%.³⁰²
Monthly injectable agents have shown promise in the treatment of obesity in adults with and without type 2 diabetes. Maridebart cafraglutide (MariTide) is a combined GLP-1 receptor agonist and GIP receptor antagonist. Results from a phase 2 clinical trial suggest this pharmacotherapy produces clinically significant weight loss compared with placebo.³⁰³

Several other pharmacotherapies are used off label, including lisdexamfetamine and a combination of phentermine and topiramate, but none are Therapeutic Goods Administration-approved for weight loss in Australia.