Type 2 diabetes in adults: management

Modified-release metformin

NICE's guideline on type 2 diabetes in adults recommends starting metformin with a modified-release formulation. There was limited evidence comparing standard-release and modified-release metformin. However, it was agreed that there are benefits to recommending modified-release metformin first. Compared with standard-release metformin, it has similar clinical effectiveness on HbA1c and weight reduction and similar safety results for hypoglycaemia but is associated with reduced gastrointestinal adverse events. Though the price of modified-release metformin can fluctuate, in December 2025 it cost less than standard-release metformin.

Standard-release metformin tablets (which can be crushed and mixed with soft food) or metformin in liquid form may be preferable for people with swallowing difficulties. The guideline also recommends that people currently taking standard-release metformin can continue on this, or switch to modified release if standard release is not tolerated or the person prefers.

See the section on initial medicines for people with type 2 diabetes and no relevant comorbidities in NICE's guideline on type 2 diabetes in adults.

SGLT-2 inhibitors

For most people with type 2 diabetes, the initial treatment recommended by NICE is modified-release metformin and an SGLT-2 inhibitor, or monotherapy with an SGLT-2 inhibitor if metformin is contraindicated or not tolerated. When frailty makes SGLT-2 inhibitors unsuitable because of their adverse effects, metformin alone is recommended.

Overall, combining metformin with an SGLT-2 inhibitor was found to be more clinically effective than metformin alone or any other combination of metformin and another medicine at reducing:

Some SGLT-2 inhibitors also reduce the risk of end-stage renal failure.

Weighing these cardiovascular and renal benefits against the risk of adverse effects with SGLT-2 inhibitors (such as volume depletion and genital mycotic infections), it was agreed that, for most people, the benefits would outweigh the risks. However, whether or not to take an SGLT-2 inhibitor alongside metformin should be a shared decision made with each person before treatment, taking into account the person's individual needs and circumstances.

The evidence of benefit from SGLT-2 inhibitors was identified in a diverse group of people. Some had multiple cardiovascular risk factors or existing atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. Others are likely to have had a lower cardiovascular risk. None of the evidence came solely from a group of people with type 2 diabetes but no comorbidities or other cardiovascular risk factors, who would all be at a relatively lower cardiovascular risk (including those who would otherwise be identified to have a QRISK score below 10%). However, all people with type 2 diabetes have an inherent increased lifetime risk of cardiovascular disease compared with people without type 2 diabetes. So, metformin with an SGLT-2 inhibitor is recommended to reduce this risk for all people with type 2 diabetes.

None of the evidence came from a group including only people with early onset type 2 diabetes. However, these people have a high lifetime risk of cardiovascular and renal complications, and are more likely to be living with obesity, so early intensive treatment can provide benefits.

SGLT-2 inhibitors were cost effective in people with type 2 diabetes and heart failure, chronic kidney disease, atherosclerotic cardiovascular disease, or living with obesity. Based on the clinical evidence, cost-effectiveness evidence and the health inequalities report, SGLT-2 inhibitors and metformin are recommended for all groups covered in the guideline, apart from those for whom they would not be clinically appropriate (that is, people with a level of frailty that would place them at risk of adverse events from SGLT-2 inhibitors).

When more than 1 medicine from the same drug class are equally suitable for the person, the guideline recommends using the least expensive one. Though dapagliflozin is not specifically recommended, NICE is aware of the large reduction in price of generic dapagliflozin and supports its use while it is the least expensive of the SGLT-2 inhibitors that may be suitable.

For details, see the sections on:

GLP-1 receptor agonists or tirzepatide

Initial treatment with a GLP-1 receptor agonist or tirzepatide, added to metformin and an SGLT-2 inhibitor, is recommended by NICE for some groups at higher cardiovascular risk. Subcutaneous semaglutide (Ozempic), up to 1 mg once a week, is recommended for people with type 2 diabetes and atherosclerotic cardiovascular disease. Any GLP-1 receptor agonist or tirzepatide can be considered for people with early onset type 2 diabetes.

In a group of people with type 2 diabetes that included a large proportion of people with atherosclerotic cardiovascular disease, subcutaneous semaglutide was the most cost-effective and clinically effective GLP-1 receptor agonist, leading to reductions in HbA1c, weight and cardiovascular events. Evidence was identified only for doses of up to 1 mg of subcutaneous semaglutide once a week. Evidence was not available to NICE to evaluate tirzepatide for this population at this time.

None of the evidence came from a group solely including people with early onset type 2 diabetes. However, it was agreed that evidence of a reduction in risk of cardiovascular and renal events in a group of people with type 2 diabetes that did not have an early onset could be extrapolated to people with early onset type 2 diabetes. It was also agreed that these benefits could be increased with long-term use. The health economic evidence for this group was highly uncertain. However, it was agreed that GLP-1 receptor agonists or tirzepatide should be considered in addition to metformin and an SGLT-2 inhibitor, given the relatively small size of this group, the health inequalities that this group would face if they did not receive treatment early, and challenges in identifying appropriate data.

The recommendation for people with early onset diabetes is to consider any GLP-1 receptor agonist or tirzepatide. However, a shared decision should be made about this with the person ahead of treatment, taking into account each person's:

For people with type 2 diabetes living with obesity, any GLP-1 receptor agonist or tirzepatide can be considered as additional treatment if the person has been taking initial therapy for at least 3 months and further medicines are needed to reach their individualised glycaemic targets.

If weight reduction is the primary aim of treatment, healthcare professionals should follow NICE's guideline on overweight and obesity management instead of the guideline on type 2 diabetes in adults.

See also the following sections in NICE's guideline on type 2 diabetes:

Other medicines for further treatment

For most people with type 2 diabetes who need further medicines to reach their individualised glycaemic targets, NICE recommends adding a DPP-4 inhibitor to the person's current treatment. If this is not suitable or not effective, it recommends adding a sulfonylurea, pioglitazone or an insulin-based treatment, as appropriate to the individual person's circumstances.

Combining a GLP-1 receptor agonist or tirzepatide with a DPP-4 inhibitor is not recommended to treat type 2 diabetes. This is because they have similar mechanisms of action, so combining them is unlikely to provide any additional benefit.