Choosing between incretins and bolus insulin is a key decision for many people with diabetes, particularly those with type 2 diabetes requiring treatment intensification. Incretins—including GLP-1 receptor agonists and DPP-4 inhibitors—work by enhancing the body's natural insulin response to food, whilst bolus insulin directly replaces mealtime insulin. Both approaches can improve blood glucose control, but they differ significantly in how they work, their side effects, and who they suit best. Understanding these differences, alongside UK guidance from NICE and the NHS, helps ensure the right treatment is selected for your individual circumstances, balancing effectiveness, safety, and quality of life.

What Are Incretins and Bolus Insulin?

Incretins are a class of glucose-lowering medications that work by mimicking or enhancing naturally occurring hormones in the body. The two main types are GLP-1 receptor agonists (such as semaglutide, dulaglutide, and liraglutide) and DPP-4 inhibitors (including sitagliptin, linagliptin, and vildagliptin). These medications enhance the body's own insulin secretion in response to food and suppress glucagon release. GLP-1 receptor agonists also slow gastric emptying and promote satiety, often leading to weight loss. By contrast, DPP-4 inhibitors are generally weight-neutral and do not meaningfully affect gastric emptying or appetite. GLP-1 receptor agonists are administered by subcutaneous injection (daily or weekly, depending on the formulation), whilst DPP-4 inhibitors are taken orally. Both incretin classes are particularly effective at reducing post-meal glucose spikes. Incretins are licensed for type 2 diabetes only and are not indicated for type 1 diabetes.

Bolus insulin, by contrast, is rapid-acting or short-acting insulin administered before (or, in some cases, shortly after) meals to control the rise in blood glucose that occurs after eating. Common rapid-acting analogues include insulin aspart (NovoRapid), faster aspart (Fiasp), insulin lispro (Humalog), and insulin glulisine (Apidra). Short-acting soluble insulin (such as Actrapid or Humulin S) is also used. Bolus insulin works by directly replacing or supplementing the body's natural mealtime insulin response, allowing glucose to enter cells for energy. Rapid-acting analogues are typically injected subcutaneously immediately before eating (or, for faster aspart, at the start of or within 20 minutes after starting a meal), whilst soluble insulin usually requires administration 30–45 minutes before meals. The dose is calculated based on carbohydrate intake and pre-meal glucose levels. Bolus insulin is a cornerstone of intensive insulin therapy, particularly for people with type 1 diabetes or advanced type 2 diabetes.

Both treatment options aim to improve glycaemic control, but they differ fundamentally in their mechanisms of action, administration requirements, and suitability for different patient populations. Understanding these differences is essential when considering which therapy may be most appropriate for individual circumstances.

Comparing Effectiveness: Incretins vs Bolus Insulin

When comparing effectiveness, both incretins and bolus insulin can significantly improve glycaemic control, but their performance varies depending on clinical context and patient characteristics. Bolus insulin provides predictable and potent glucose-lowering effects, with no maximum dose limitation—the dose can be titrated upwards as needed to achieve target HbA1c levels. Clinical trials demonstrate that intensive insulin regimens (basal-bolus therapy) can reduce HbA1c by 1.5–2.5% or more in people with poorly controlled type 2 diabetes. This makes bolus insulin particularly valuable when substantial glucose reduction is required or when other therapies have proven insufficient.

GLP-1 receptor agonists have shown comparable or sometimes superior HbA1c reductions in head-to-head trials. Studies comparing GLP-1 agonists with bolus insulin in people already taking basal insulin have demonstrated similar glycaemic improvements, with HbA1c reductions typically ranging from 1.0–1.8%. Trials such as AWARD-9, DURATION-7, 4B, GetGoal-Duo2, and DUAL VII have shown that adding a GLP-1 agonist to basal insulin can achieve glycaemic targets without the need for multiple daily injections. NICE guidance (NG28) recognises GLP-1 receptor agonists as an alternative to intensifying insulin therapy in type 2 diabetes, particularly when weight gain or hypoglycaemia are concerns and within licensed indications.

DPP-4 inhibitors generally produce more modest HbA1c reductions (0.5–1.0%) compared with either bolus insulin or GLP-1 agonists, making them less suitable when substantial glucose lowering is required. However, they offer convenience as oral medications and may be appropriate for people with milder hyperglycaemia.

A key consideration is hypoglycaemia risk. Bolus insulin carries a significantly higher risk of hypoglycaemic episodes, particularly if meals are delayed or carbohydrate intake is miscalculated. Incretins, by contrast, have a glucose-dependent mechanism—they stimulate insulin secretion only when blood glucose is elevated—resulting in substantially lower hypoglycaemia rates when used alone. However, when GLP-1 receptor agonists are combined with insulin or sulfonylureas, the risk of hypoglycaemia increases, and dose reduction of the insulin or sulfonylurea may be required under medical supervision. This safety advantage is particularly relevant for older adults or those at high risk of hypoglycaemia-related complications.

Side Effects and Safety Considerations

The side effect profiles of incretins and bolus insulin differ considerably, influencing treatment selection and patient acceptability. Bolus insulin's primary safety concern is hypoglycaemia, which can range from mild symptoms (tremor, sweating, palpitations) to severe episodes requiring third-party assistance. The risk increases with intensive insulin regimens, irregular eating patterns, alcohol consumption, or increased physical activity. Patients require education on recognising and treating hypoglycaemia, and some may experience problematic hypoglycaemia unawareness. Additionally, insulin therapy is associated with weight gain, typically 2–4 kg when initiating or intensifying treatment, which can be concerning for people with type 2 diabetes who are already overweight.

Other insulin-related adverse effects include injection site reactions (lipohypertrophy, bruising, or rarely lipoatrophy) and the psychological burden of multiple daily injections, which can affect treatment adherence and quality of life.

GLP-1 receptor agonists most commonly cause gastrointestinal side effects, including nausea (reported in 20–40% of users), vomiting, diarrhoea, and constipation. These symptoms are usually transient, improving over 4–8 weeks, and can be minimised by gradual dose titration. Unlike insulin, GLP-1 agonists typically promote weight loss (average 2–6 kg), which many patients find beneficial. Important safety considerations include an increased risk of gallbladder disease (cholelithiasis and cholecystitis). Semaglutide has been associated with worsening of diabetic retinopathy, particularly in patients with pre-existing retinopathy who experience rapid glycaemic improvement; retinopathy monitoring is advised in such patients. Acute pancreatitis has been reported with GLP-1 agonists; patients should be advised to stop treatment and seek immediate medical attention if persistent severe abdominal pain occurs. Rodent studies have shown C-cell tumours with GLP-1 receptor agonists, though the relevance to humans is uncertain; this is not a contraindication in the UK or EU. If insulin is rapidly reduced or discontinued when starting a GLP-1 agonist, there is a risk of diabetic ketoacidosis, particularly in type 1 diabetes (where GLP-1 agonists are not licensed).

DPP-4 inhibitors are generally well-tolerated with minimal side effects. Nasopharyngitis and headache are reported. Post-marketing surveillance has identified rare but important adverse effects: heart failure risk (particularly with saxagliptin and alogliptin), bullous pemphigoid, severe arthralgia, and pancreatitis. Vildagliptin requires liver function test monitoring before treatment and periodically thereafter.

Both incretins and insulin require consideration of renal function. Dose adjustments or alternative agents may be necessary in moderate to severe renal impairment. For example, exenatide is contraindicated at eGFR <30 mL/min/1.73 m², whilst most DPP-4 inhibitors require dose adjustment except linagliptin. The MHRA and individual Summaries of Product Characteristics (SmPCs) provide specific guidance for each medication. Patients should be counselled on recognising adverse effects and when to seek medical attention, particularly for severe gastrointestinal symptoms, signs of pancreatitis (persistent severe abdominal pain), recurrent hypoglycaemia, or symptoms of heart failure. Suspected adverse drug reactions should be reported via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk.

Which Treatment Is Right for You?

Selecting between incretins and bolus insulin requires individualised assessment, considering multiple clinical and personal factors. NICE guidance (NG28) provides a framework for treatment intensification in type 2 diabetes. When intensifying therapy beyond basal insulin, NICE recommends considering a GLP-1 receptor agonist instead of starting bolus insulin in appropriate people—for example, if weight gain or hypoglycaemia are concerns—within licensed indications. GLP-1 receptor agonists may be particularly suitable when BMI is ≥35 kg/m² (or ≥32.5 kg/m² for people of South Asian or related ethnicity) or when weight loss would benefit other obesity-related comorbidities.

Bolus insulin remains the treatment of choice for type 1 diabetes, where endogenous insulin production is absent or minimal. For type 2 diabetes, bolus insulin is particularly appropriate when:

• Substantial and rapid glucose lowering is required (e.g., symptomatic hyperglycaemia or persistently high HbA1c despite optimised therapy)

• Other therapies, including incretins, have proven inadequate

• The person is willing and able to perform multiple daily injections and blood glucose monitoring

• Weight gain is not a primary concern

• Cost considerations favour insulin (generally less expensive than GLP-1 agonists)

Incretins, particularly GLP-1 receptor agonists, may be preferable when:

• Weight loss is desirable or weight gain must be avoided

• Hypoglycaemia risk is a significant concern (e.g., older adults, those living alone, occupational drivers)

• The person wishes to avoid multiple daily injections

• Cardiovascular or renal benefits are sought (certain GLP-1 agonists have demonstrated cardiovascular and renal protection in outcome trials)

Practical considerations also matter. Bolus insulin requires carbohydrate counting skills, frequent blood glucose monitoring, and dose adjustment capabilities. Incretins require tolerance of potential gastrointestinal side effects and, for GLP-1 agonists, acceptance of injectable therapy (though less frequent than bolus insulin). Fixed-ratio combinations of basal insulin and GLP-1 agonist—such as Suliqua (insulin glargine/lixisenatide) and Xultophy (insulin degludec/liraglutide)—are available in the UK and can simplify treatment for some people, reducing injection burden whilst providing both basal glucose control and GLP-1 receptor agonist benefits.

Shared decision-making is essential. Discuss your preferences, lifestyle, concerns about injections or side effects, and treatment goals with your diabetes healthcare team. Your GP or diabetes specialist nurse can help determine the most appropriate strategy based on your individual circumstances, comorbidities, and HbA1c targets. Referral to a diabetes specialist team should be considered for insulin intensification, recurrent or problematic hypoglycaemia, or suspected serious adverse effects. Regular review and adjustment of therapy ensures optimal outcomes whilst minimising treatment burden and adverse effects.

Frequently Asked Questions