Saxenda (liraglutide 3.0 mg) is a glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for weight management in adults with obesity or overweight with weight-related comorbidities. A common question is whether Saxenda increases glucagon levels. In fact, Saxenda suppresses glucagon secretion from pancreatic alpha cells when blood glucose is elevated, rather than increasing it. This glucagon-lowering effect, combined with glucose-dependent insulin enhancement, helps regulate blood sugar and supports weight loss. Understanding how Saxenda affects glucagon and other metabolic hormones is important for safe and effective use.

How Saxenda Works in the Body

Saxenda (liraglutide 3.0 mg) is a glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for weight management in adults with obesity or overweight with weight-related comorbidities. As a synthetic analogue of human GLP-1, Saxenda mimics the action of this naturally occurring incretin hormone, which is released from the intestine in response to food intake.

The primary mechanism of action involves binding to GLP-1 receptors located throughout the body, particularly in the pancreas, brain, and gastrointestinal tract. In the pancreas, Saxenda stimulates insulin secretion from beta cells in a glucose-dependent manner—meaning insulin is released primarily when blood glucose levels are elevated and this effect diminishes as glucose normalises. Simultaneously, it suppresses glucagon secretion from pancreatic alpha cells, rather than increasing it. This glucagon suppression is also glucose-dependent, occurring primarily when blood glucose levels are raised.

Beyond pancreatic effects, Saxenda acts on appetite centres in the hypothalamus to reduce hunger and increase satiety, leading to decreased caloric intake. It also slows gastric emptying, which prolongs the feeling of fullness after meals and contributes to weight loss, though this effect may attenuate with chronic use. The medication has a half-life of approximately 13 hours, allowing for once-daily subcutaneous administration.

The glucose-dependent nature of Saxenda's action is particularly important from a safety perspective, as it means the medication's effects on insulin and glucagon are modulated by prevailing blood glucose levels, reducing the risk of hypoglycaemia when used as monotherapy for weight management.

Saxenda's Effects on Blood Sugar and Hormones

Contrary to what the question implies, Saxenda does not increase glucagon—it actually suppresses glucagon secretion when blood glucose levels are elevated. This glucagon-lowering effect is one of the key mechanisms by which GLP-1 receptor agonists help regulate blood glucose homeostasis. Glucagon is a counter-regulatory hormone that raises blood glucose by promoting hepatic glucose production; by suppressing inappropriate glucagon release, Saxenda helps prevent excessive glucose output from the liver. Importantly, GLP-1 receptor agonists generally do not impair counter-regulatory glucagon responses during hypoglycaemia.

The hormonal effects of Saxenda are multifaceted and glucose-dependent. When blood glucose rises after a meal, Saxenda enhances insulin secretion from pancreatic beta cells whilst simultaneously reducing glucagon release from alpha cells. This dual action helps lower postprandial (after-meal) blood glucose levels. Importantly, as blood glucose falls towards normal levels, these effects diminish, which explains why Saxenda monotherapy carries a low risk of hypoglycaemia.

Clinical studies, including the SCALE Obesity and Prediabetes trials, have demonstrated that liraglutide treatment leads to improvements in glycaemic control markers, including reductions in HbA1c (a measure of average blood glucose over three months) and fasting plasma glucose. These effects are observed even in individuals without diabetes who use Saxenda for weight management, though the magnitude of glucose-lowering is naturally greater in those with impaired glucose regulation.

Additionally, Saxenda influences other metabolic parameters. Weight loss achieved with the medication often leads to improvements in insulin sensitivity and favourable changes in lipid profiles. Some patients experience modest reductions in blood pressure, likely related to weight loss.

What This Means for Diabetes and Weight Management

The glucagon-suppressing properties of Saxenda, combined with its glucose-dependent insulin enhancement, make it particularly relevant for individuals with obesity, including those with type 2 diabetes. However, it's important to note that Saxenda (liraglutide 3.0 mg) is specifically licensed for weight management, whilst a lower dose formulation, Victoza (liraglutide up to 1.8 mg), is licensed for type 2 diabetes treatment. The mechanisms of action are identical, but the dosing and licensed indications differ.

For weight management in people without diabetes, Saxenda's effects on glucagon and insulin help maintain stable blood glucose levels during caloric restriction and weight loss. This can prevent the compensatory increases in hunger that often undermine weight loss efforts. The medication's ability to suppress glucagon when glucose is elevated, without causing problematic hypoglycaemia, provides metabolic stability during the weight loss journey.

In individuals with prediabetes or metabolic syndrome, Saxenda may offer additional benefits beyond weight reduction. By improving the balance between insulin and glucagon, the medication can help restore more normal glucose regulation.

NICE guidance recommends considering pharmacological interventions for weight management in adults with a BMI of 30 kg/m² or above, or 27 kg/m² with weight-related comorbidities, when dietary and exercise interventions alone have been insufficient. According to the NICE Technology Appraisal for liraglutide, Saxenda should be discontinued if patients have not lost at least 5% of their initial body weight after 12 weeks at the maintenance dose, as continued treatment is unlikely to provide meaningful benefit. The medication works best as part of a comprehensive weight management programme including dietary modification, increased physical activity, and behavioural support.

Safety Considerations and Monitoring While Taking Saxenda

Whilst Saxenda does not increase glucagon and carries a low intrinsic risk of hypoglycaemia when used alone, several important safety considerations require attention. The most common adverse effects include gastrointestinal symptoms—particularly nausea, vomiting, diarrhoea, and constipation—which typically occur during dose escalation and often improve with continued use. Starting at a low dose (0.6 mg daily) and gradually increasing over five weeks helps minimise these effects.

Monitoring requirements include regular assessment of weight loss progress, tolerability, and any emerging adverse effects. Patients should be advised to stay well hydrated, especially if experiencing gastrointestinal symptoms, as dehydration can lead to acute kidney injury. Those with pre-existing renal impairment require careful monitoring. Blood pressure and heart rate should be checked periodically, as some patients experience modest increases in resting heart rate (typically 2-3 beats per minute).

Important precautions include monitoring for symptoms such as neck mass, dysphagia or hoarseness in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, as GLP-1 receptor agonists have been associated with thyroid C-cell tumours in rodent studies (though there is no established link in humans). Saxenda is not recommended in patients with severe gastrointestinal disease, including diabetic gastroparesis, due to its effects on gastric emptying. It is not recommended during pregnancy or breastfeeding.

Patients should contact their GP or healthcare provider if they experience:

• Severe, persistent abdominal pain (potential pancreatitis)

• Signs of dehydration or reduced urine output

• Symptoms of gallbladder disease (right upper abdominal pain, especially after meals)

• Persistent rapid heartbeat or palpitations

• Signs of depression or suicidal thoughts (rare but reported)

Patients should report any suspected side effects via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk).

For individuals taking Saxenda alongside other glucose-lowering medications (particularly insulin or sulfonylureas), dose adjustments of these medications may be necessary to prevent hypoglycaemia, and closer blood glucose monitoring is essential. Regular follow-up with healthcare professionals ensures optimal safety and effectiveness throughout treatment.

Frequently Asked Questions