Reference

Type 2 diabetes in adults: management NICE guideline. Last updated: 29 June 2022

Abbreviations

ASCVD: atherosclerotic cardiovascular disease
CKD: chronic kidney disease with estimated glomerular filtration rate [eGFR] 20–60 mL/min/1.73 m2 and/or albuminuria
MASLD: Metabolic dysfunction–associated steatotic liver disease
Non-steroidal MRA: non-steroidal mineralocorticoid receptor antagonist (e.g. Finerenone),
Steroidal MRA: steroidal mineralocorticoid receptor antagonists (e.g. spironolactone or eplerenone)
GLP-1 RA: Glucagon-like peptide 1 (GLP-1) receptor agonist
GIP/GLP-1 RA: Dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist
SGLT-2i: Sodium–glucose cotransporter 2 inhibitor
DPP-4i: Dipeptidyl peptidase 4 inhibitors

Quiz (Answer True or False)

True.
Offer referral to a structured group education programme such as the DESMOND (Diabetes Education for Self-Management for Ongoing and Newly Diagnosed) programme, for the person and their family/carers.
False.
HbA1c monitoring is invalid because of disturbed erythrocyte turnover or abnormal haemoglobin type. Fructosamine or CGM can be used for glycaemic monitoring when an alternative to HbA1cis required.
True.
True.
Do not routinely offer self-monitoring of capillary blood glucose levels for adults with type 2 diabetes unless:
- the person is on insulin or
- there is evidence of hypoglycaemic episodes or
- the person is on oral medication that may increase their risk of hypoglycaemia while driving or operating machinery or
- the person is pregnant or is planning to become pregnant.
False.
Continuous glucose monitoring (CGM) may be intermittently scanned (isCGM) or real-time (rtCGM).
CGM may benefit individuals who experience recurrent or severe hypoglycaemia or have impaired hypoglycaemia awareness. CGM users will still need to take capillary blood glucose measurements to check the accuracy of their CGM device and act as as a back-up if the CGM system fails.
True.
False.
Before starting an SGLT2 inhibitor, check whether the person may be at increased risk of diabetic ketoacidosis (DKA), for example if:
- they have had a previous episode of DKA
- they are unwell with intercurrent illness
- they are following a very low carbohydrate or ketogenic diet.
High risk of developing cardiovascular disease is defined as:
- QRISK2 more than 10% in adults aged 40 and over or
- an elevated lifetime risk of cardiovascular disease (defined as the presence of ONE or more cardiovascular risk factors in someone under 40).
Cardiovascular disease risk factors:
hypertension
dyslipidaemia
smoking
obesity
family history of premature cardiovascular disease.
True.
Triple therapy (metformin, another oral drug (e.g. SGLT2 inhibitor), and GLP-1 RA) is indication in adults with type 2 diabetes who:
- have a body mass index (BMI) of 35 kg/m2 or higher (adjust accordingly for people from Black, Asian and other minority ethnic groups) and specific psychological or other medical problems associated with obesity or
- have a BMI lower than 35 kg/m2 and:
  - for whom insulin therapy would have significant occupational implications or
  - weight loss would benefit other significant obesity-related comorbidities.
True.
Only continue GLP-1 RA therapy if the adult with type 2 diabetes has had a beneficial metabolic response (a reduction of at least 11 mmol/mol [1.0%] in HbA1c and weight loss of at least 3% of initial body weight in 6 months).
True.
True.
Consider periodic assessment of vitamin B12 level in metformin-treated individuals, especially in those with anaemia or peripheral neuropathy.
False.

Definition

Type 2 diabetes is caused by a combination of
insulin resistance and
relative insulin deficiency (where the pancreas is unable to secrete enough insulin to compensate for this resistance)

Pathophysiology

Diagnosis (HbA1C ≥6.5% (≥48 mmol/mol)

Management

Type 2 diabetes and glucose-lowering therapeutic agents

NICE guideline, monotherapy: Offer standard-release metformin as first-line treatment, unless it is contraindicated.
NICE guideline, dual therapy: If monotherapy is ineffective, consider adding DPP-4i or Pioglitazone or Sulfonylurea or SGLT-2i
NICE guideline, triple therapy: Consider adding, DPP-4i or Pioglitazone or Sulfonylurea or SGLT-2i, OR, initiating insulin.
NICE guideline, triple therapy ineffective or not tolerated: substitute one drug for GLP-1 RA or dual GIP/GLP-1 RA

ADA guideline: To achieve both glycaemic and weight management goals, prioritise agents that induce weight loss:
Weight loss >10%: GLP-1 RA, dual GIP/GLP-1 RA
Weight loss <10%: SGLT-2i, metformin
Weight neutral: DPP-4i
Weight gain: sulfonylureas, thiazolidinediones, and **insulin
*Concurrent use of DPP-4i with a GLP-1 RA or a dual GIP/GLP-1 RA is not recommended.
**Consider initiating insulin if symptoms of hyperglycemia or when HBA1c is very high (>10% or >86 mmol/mol)
If insulin is used, consider combination therapy with a GLP-1 RA or dual GIP/GLP-1 RA, for greater glycaemic effectiveness as well as beneficial effects on weight and hypoglycemia risk.

Type 2 diabetes and overweight/obesity
Sustained loss of >10% of body weight confers disease-modifying effects and possible remission of type 2 diabetes (particularly if new-onset diabetes within 6 years).

Consider a short-term nutrition intervention e.g. very-low-calorie meals (800 kcal/day): NHS Type 2 Diabetes Path to Remission Programme
Pharmacotherapy e.g. GLP-1 RA, dual GIP/GLP-1 RA.
Bariatric/Metabolic surgery, recommended by NICE, if
Poorly controlled type 2 diabetes AND BMI ≥35.0 kg/m2 OR
Poorly controlled type 2 diabetes and diabetes is of short duration (<10 years) and BMI is 30-34.9 kg/m2

Type 2 diabetes and established or high-risk ASCVD OR Heart Failure (HFrEF, HFpEF)
NICE guideline: offer an SGLT-2i with proven cardiovascular benefit in addition to metformin.
ADA guideline: GLP-1 RA and SGLT-2i are recommended or both glycaemic management and cardiovascular risk reduction.

Type 2 diabetes and CKD
Optimise blood pressure management (aim for <130/80 mmHg).
ACE inhibitor or an angiotensin receptor blocker (ARB) is recommended if eGFR <60 mL/min/1.73 m2 and/or increased albuminuria, to maximally tolerated dose to prevent the progression of kidney disease and reduce cardiovascular events.
An SGLT2i or GLP-1 RA will slow progression of CKD and reduce adverse cardiovascular events.
The glycemic benefits of SGLT2i is reduced at eGFR <45 mL/min/1.73 m2.
If CKD Stage 3 and 4 with albuminuria, and serum potassium ≤5 mmol/L, then initiate Finerenone (a non-steroidal MRA).

Type 2 diabetes AND MASLD AND overweight/obesity
Consider GLP-1RA, or dual GIP/GLP-1 RA.

What are the treatment targets for adults with type 2 diabetes?

Lifestyle including diet management — 48 mmol/mol (6.5%).

Lifestyle including diet PLUS single drug not associated with hypoglycaemia (such as metformin) — 48 mmol/mol (6.5%).
Drug treatment associated with hypoglycaemia (such as a sulfonylurea): 53 mmol/mol (7.0%).
Measure HbA1c levels at 3–6-monthly intervals (tailored to individual needs) until the HbA1c is stable on unchanging treatment, then at 6-monthly intervals.
If HbA1c levels are not adequately controlled by a single drug and rise to 58 mmol/mol (7.5%) or higher:
intensify antidiabetic drug treatment.

Consider relaxing the target HbA1c level if:

The person is unlikely to achieve longer-term risk-reduction benefits, for example they have a reduced life expectancy.
Tight blood glucose control poses a high risk of the consequences of hypoglycaemia, for example in people who are at risk of falling, people who have impaired awareness of hypoglycaemia, and people who drive or operate machinery as part of their job.
Intensive management would be inappropriate, for example in a person with significant comorbidities.

RESCUE therapy at any phase of treatment

If an adult with type 2 diabetes is symptomatically hyperglycaemic, consider insulin or a sulfonylurea, and review treatment when blood glucose control has been achieved.