Section 1 – Janet

Janet, a 65-year-old Caucasian woman, has had type 2 diabetes for 14 years. She has background retinopathy but is otherwise without serious medical problems.

Current medication:

• Metformin 1 g twice daily.
• Dapagliflozin 10 mg once daily.
• Semaglutide 1 mg subcutaneously once weekly.
• Losartan 100 mg once daily.
• Atorvastatin 20 mg once daily.

Recent results:

• HbA_1c 68 mmol/mol (8.4%).
• eGFR 63 mL/min/1.73 m².
• Total cholesterol 3.6 mmol/L; non-HDL cholesterol 2.4 mmol/L.
• LFTs normal.
• Urinary ACR <3 mg/mmol.
• BMI 30.2 kg/m².
• Blood pressure 133/73 mmHg.

What would be your target HbA_1c for Janet?

Section 2

NICE (2025) guidelines for type 2 diabetes set an “ideal” HbA_1c target of 53 mmol/mol (7.0%) on multiple therapy for hyperglycaemia. This could reasonably be revised upward, however, if medication side effects and issues such as hypoglycaemia become problematic.

How would you seek to manage Janet’s hyperglycaemia and why?

Section 3

Firstly, reinforce lifestyle measures aimed at improving hyperglycaemia. Janet cannot identify any easily correctable issues to account for the rise in her HbA_1c, and so we need to consider escalating her glucose-lowering therapy.

Considering oral glucose-lowering medication options first:

DPP-4 inhibitors (gliptins): As Janet is already using a GLP-1 receptor agonist (GLP-1 RA), addition of a DPP-4 inhibitor – a less powerful incretin-based agent – is regarded as unhelpful (ADA Professional Practice Committee for Diabetes, 2026).

Pioglitazone is an option but may lead to unacceptable side effects, including fluid retention, weight gain and heart failure, and an increased risk of osteoporosis and possibly bladder cancer (Dormandy et al, 2005; Lewis et al, 2015). There also remains a concern over increased fracture risk, which would weigh against the use of pioglitazone in a post-menopausal woman such as Janet.

Sulfonylurea: Checking Janet’s medication history, she has previously used gliclazide but this was discontinued in favour of other glucose-lowering agents, owing to hypoglycaemia and weight gain. After 14 years of diabetes, Janet’s beta-cell function may now have declined to the extent that stimulation of insulin release would be ineffective (Davies et al, 2018).

Whilst insulin resistance is one of the defining features of type 2 diabetes, insulin deficiency becomes increasingly likely as duration of type 2 diabetes increases and beta-cell function declines. If endogenous insulin supply is running low, introduction of exogenous insulin therapy is a logical strategy and the most likely treatment to get Janet towards her HbA_1c target.

A basal insulin is the most common and simplest starting point for insulin therapy in people with type 2 diabetes (NICE, 2025; ADA Professional Practice Committee for Diabetes, 2026), and has the advantage of causing less hypoglycaemia and weight gain than regimens that use a pre-mixed biphasic insulin or add in a prandial insulin (Ilag et al, 2007).

What are the problems and disadvantages of using insulin?

Section 4

Problems with using insulin include:

• The need to inject.
• Requirement for regular glucose monitoring.
• Stricter rules for driving.
• Complexity of dose titration.
• Risk of hypoglycaemia.
• Weight gain.
• Potential psychological factors.

An intensive education package from an appropriately trained healthcare professional should always accompany insulin initiation (NICE, 2025; ADA Professional Practice Committee for Diabetes, 2026).

Even when there are convincing reasons to start insulin, a variety of factors may confound this. Fear of hypoglycaemia and weight gain, an unwillingness to monitor glucose and needle phobia are all reasons why people with type 2 diabetes may seek to avoid insulin therapy. For some, starting insulin might result in loss (or at least disruption) of employment; this is notably the case for drivers of large goods vehicles and passenger-carrying vehicles. Such individuals may choose to delay insulin initiation and accept suboptimal glycaemic levels.

In addition, health beliefs and issues around how insulin use may have been communicated in past may be barriers to taking up insulin therapy (for example, people are often incorrectly advised that “they will end up on insulin” if they do not follow advice).

The decision to commence insulin therapy for type 2 diabetes should only be arrived at after full discussion and with shared decision-making at the centre of the person’s care.

Janet considers a basal insulin regimen as her best option for glycaemic management. She is referred to the Community Diabetes Specialist Nurse for initiation of a basal insulin, together with the necessary education.

What are the key educational requirements when starting insulin?

Section 5

Education and empowerment of the person with diabetes are key to the success of instituting insulin therapy. Essential points to be covered are listed below (NICE, 2025):

• Injection technique and site rotation.
• Sharps disposal.
• Self-monitoring of blood glucose.
• Self-adjustment of insulin dose.
• Recognition and response to hypoglycaemia.
• Sick day guidance.
• Insurance and driving implications.
• Storage conditions for insulin, including travel arrangements.
• Point of contact for any problems.

Janet is commenced on a biosimilar insulin glargine at an initial dose of 10 units per day. More detail on when to start insulin, available basal insulins and starting doses can be found at the end of these case studies.

How can Janet’s dose of basal insulin be safely uptitrated from here?

Section 6

The supervision of insulin initiation and uptitration, as well as review of injection technique, is commonly performed by specialist diabetes services, but it is useful for primary care to have a working knowledge of this process.

In the case of a once-daily basal insulin, usually given in the evening, the insulin dose can be uptitrated according to morning (fasting) capillary glucose readings. Potentially, this could be undertaken in General Practice.

Thus, in Janet’s case, the insulin could be uptitrated from an initial daily dose of 10 units by 2 units every 4–5 days, aiming for morning capillary glucose readings in the range of 5–8 mmol/L (NICE, 2025).

If the dose of insulin becomes significantly higher (e.g. around 40 units daily), then the dose should be increased more quickly (for example, by 4 units every 4–5 days, i.e. approximately 10% of the total dose).

When adding insulin to the glucose-lowering regimen of a person with type 2 diabetes, what would be your position on continuing non-insulin treatments?

Section 7

In general, aim to continue metformin, SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 or GIP/GLP-1 receptor agonists, as these can reduce insulin requirements. Metformin can provide cardiovascular protection, whilst SGLT2 inhibitors and certain incretin therapies offer cardiorenal benefits and, by inducing weight loss, help mitigate the weight gain associated with insulin use (ADA Professional Practice Committee for Diabetes, 2026).

However, the combination of insulin with pioglitazone may increase the risk of fluid retention and heart failure, so caution is needed here. Sulfonylureas (and meglitinides such as repaglinide) further increase the risk of hypoglycaemia when used in combination with insulin, and consideration should be given to stopping these treatments when insulin is initiated, and certainly if the insulin regimen contains a prandial insulin component. Sulfonylureas are often continued with basal insulin if they have been effective but are stopped for pre-mixed and prandial insulin regimens.

Janet asks you about symptoms of hypoglycaemia and how she should treat it. How would you advise her?

Section 8

Janet should be warned about the autonomic symptoms of hypoglycaemia; these occur secondary to the corrective autonomic response of adrenalin, and include sweating, tremor, palpitations, nausea, hunger and a tingling sensation around the mouth.

A further set of neuroglycopenic symptoms Janet and her partner need to be aware of, reflecting an inadequate supply of glucose to the brain, include blurred vision, speech difficulty, dizziness, confusion, irritability and, eventually, seizures and coma.

If hypoglycaemic awareness is reduced (see At a glance factsheet: Impaired hypoglycaemia awareness), it may be necessary to allow glucose readings to run higher than ideal levels.

Treating hypoglycaemia

Advise Janet to always carry a supply of fast-acting carbohydrate with her to deal with impending hypoglycaemia. In cases of mild hypoglycaemia, 15–20 g of fast-acting carbohydrate should be given. Some examples of suitable oral treatments are as follows (Milne and Thomas, 2025):

• Five to seven dextrose tablets.
• Five glucose tablets.
• Four large jelly babies.
• 200 mL pure fruit juice.
• Two tubes of glucose gel (e.g. Glucogel, Dextrogel).
• One 60 mL Lift (Formerly GlucoJuice) juice shot.

Treatment can be repeated after 10–15 minutes if symptoms persist or if blood glucose remains <4 mmol/L. It is good advice to then take on board a longer-acting starchy carbohydrate snack, such as a banana, sandwich or cereal bar, to maintain glucose levels subsequently.

Janet asks you what action she needs to take in regard to her driving now that she is using insulin. What basic advice could you offer her?

Section 9

Janet has a group 1 (car and motorcycle) licence. The key actions that Janet needs to know are (DVLA, 2025):

• Notify the DVLA and her driving insurance company that she is using insulin.
• Check glucose levels before driving, and every 2 hours thereafter if continuing to drive.
• If glucose levels are <5 mmol/L, take on board a longer-acting carbohydrate. “Do not drive below five”.
• Carry rapid-acting carbohydrate for treating hypoglycaemia.
• Carry glucose monitoring equipment. This could include continuous glucose monitoring and/or fingerprick glucose monitoring.

If symptoms of hypoglycaemia occur when driving:

• Pull over and stop the car in a safe location.
• Remove keys from the ignition and move out of the driver’s seat.
• Treat the hypoglycaemia.
• Do not drive until 45 minutes after glucose levels have returned to normal (at least 5 mmol/L).

Several months later, Janet sees you for a matter unrelated to diabetes, but mentions that she has been experiencing symptoms of hypoglycaemia at night-time. Her dose of biosimilar insulin glargine is now 28 units pre-bedtime.

What action would you advise Janet to take to avoid nocturnal hypoglycaemia?

Section 10

You should advise Janet to reduce her evening dose of insulin by 10–20%, or to revert to the previous dose at which she did not experience hypoglycaemia.

Janet’s dose is reduced to 24 units pre-bedtime. She is encouraged to carefully monitor her morning glucose levels and to contact the Diabetes Specialist Nurse for further advice.

This ends Janet’s case study.

Section 11 – Raj

Raj is 59 years old, of South Asian ethnicity, and has had type 2 diabetes for 11 years. He has diabetic nephropathy and diabetic retinopathy, and suffered a myocardial infarction 4 years ago.

Medication:

• Metformin modified-release 1 g once daily.
• Gliclazide 160 mg twice daily.
• Empagliflozin 10 mg once daily.
• Linagliptin 5 mg once daily.
• Aspirin 75 mg once daily.
• Bisoprolol 5 mg once daily.
• Ramipril 10 mg once daily.
• Atorvastatin 80 mg once daily.

Recent results:

• HbA_1c 81 mmol/mol (9.6%).
• eGFR 38 mL/min/1.73 m².
• Urinary ACR 27 mg/mmol.
• BMI 29.1 kg/m².

How would you try to improve Raj’s glycaemic control?

Section 12

Firstly, check that Raj is tolerating and correctly taking his glucose-lowering medications. Ask him if he would like to discuss lifestyle measures, including diet, physical activity, sleep and stress/emotional wellbeing.

Raj’s dose of metformin cannot safely be increased because of his low eGFR (due to risk of lactic acidosis) (Inzucchi et al, 2014). The glycaemic-lowering efficacy of SGLT2 inhibitors declines with falling eGFR, although his empagliflozin should nonetheless be continued because the cardiorenal protection offered by SGLT2 inhibitors is maintained at lower eGFR values (Heerspink et al, 2020; Herrington et al, 2023; NICE, 2025). Pioglitazone is an option in chronic kidney disease but, as mentioned in Janet’s case study, has a range of possible side effects and concerns, and it is unlikely to achieve the desired glucose levels.

It is decided to try a GLP-1 RA injection (with discontinuation of linagliptin). Unfortunately, Raj experiences persistent nausea and gastrointestinal upset with two different GLP-1 RAs.

What might be your next treatment option for Raj?

Section 13

Insulin looks to be the best option now, and Raj is referred to the secondary care diabetes clinic with this in mind. After dose titration, Raj is established on 48 units of a basal insulin.

A year later, his HbA_1c has fallen to 68 mmol/mol (8.4%). Morning blood glucose levels are now reasonably controlled, in the range of 5–9 mmol/L. Raj is asked to record pre-lunch, pre-evening-meal and pre-bedtime glucose readings, and these turn out to be in the range of 9–18 mmol/L.

What would be the next step in optimising Raj’s glucose levels?

Section 14

Raj’s insulin regimen needs to be intensified to include a prandial (mealtime) insulin component alongside the basal insulin. This would allow optimisation of his daytime glucose readings.

There are two principal ways of achieving this (Vanderpant et al, 2024):

Option 1: Replace the basal insulin with a biphasic pre-mixed insulin (a short-acting insulin combined with an intermediate-acting insulin) twice daily. This is appropriate if Raj has regular meal content and timings.

• This could be a pre-mixed human insulin preparation (e.g. Humulin® M3), or alternatively a pre-mixed insulin analogue preparation (e.g. Novomix® 30, Humalog® Mix 25 or 50).

Option 2: Add in prandial doses of a short-acting insulin, with one to three meals a day, alongside the basal insulin. This offers more flexibility if meal content and timings are variable.

• This could involve adding either a rapid-acting insulin analogue (e.g. Apidra®, NovoRapid®, Humalog®, Trurapi®, Fiasp®, Lyumjev®), or a short-acting soluble human insulin (e.g. Actrapid®, Humulin® S) to the basal insulin.

Raj is referred to the local diabetes clinic, where he is commenced on a twice-daily biphasic mixed insulin, 32 units taken with breakfast and 16 units with the evening meal, to replace his basal insulin.

The gliclazide is discontinued and Raj continues to take metformin and empagliflozin. The biphasic insulin is uptitrated according to daily glucose readings.

Raj contacts the surgery during an episode of diarrhoea and vomiting. What advice would you give him?

Section 15

Advise Raj to (Down, 2020):

• Continue his twice-daily biphasic insulin.
• Temporarily discontinue his metformin (risk of lactic acidosis), empagliflozin (risk of diabetic ketoacidosis) and ramipril (risk of acute kidney injury).
• Maintain a good fluid intake, with regular sipping if necessary: water, tea, milk or fruit juice (at least 100 mL/hour).
• Aim for a simple, light diet containing carbohydrates.
• Regularly monitor glucose levels.
• If blood glucose levels are low, take sugary fluids.
• If blood glucose levels are 11–17 mmol/L, take 2 units extra of biphasic insulin. If 17–22 mmol/L, take 4 units extra. If >22 mmol/L, take 6 units extra.
• If vomiting persists or blood glucose levels are persistently >22 mmol/L, or if he has symptoms of diabetic ketoacidosis or tests positive for ketones, then seek urgent medical advice.

This ends Raj’s case study. The final two sections provide a recap of when insulin therapy is appropriate and on starting a basal insulin regimen.

Section 16 – When might insulin therapy be appropriate in people with type 2 diabetes?

• When lifestyle and non-insulin therapies are unable to achieve the individual’s target HbA_1c (NICE, 2025; ADA Professional Practice Committee for Diabetes, 2026). See Janet’s case study.
• When there is intolerance or contraindication to non-insulin based treatments. See Raj’s case history.
• When HbA_1c is very high (>86 mmol/mol) or there are osmotic symptoms (polyuria, polydipsia, weight loss) (ADA Professional Practice Committee for Diabetes, 2026). See How to: Rescue therapy in the management of type 2 diabetes.
• When there is uncertainty over the diagnosis of type 2 diabetes – where autoimmune or pancreatogenic diabetes is suspected, insulin is the safest treatment option.
• In pregnancy, where tight glycaemic control is crucial to avoid maternal and neonatal problems. Whilst lifestyle change and metformin may be tried initially, the preferred treatment option, for safety and efficacy, is insulin (NICE, 2020).
• In situations of acute illness or surgery, insulin may be necessary to achieve satisfactory glycaemic control and to avoid the risk of toxicity from other agents.

NICE (2025) positions insulin as one of the options for triple therapy in the treatment of type 2 diabetes, such that it may be used as an add-on to dual oral therapy when HbA_1c has risen above 58 mmol/mol. ADA guidelines recommend a basal insulin as one possible second-line option to add to metformin, as an alternative to other oral therapies and GLP-1 RA injections (ADA Professional Practice Committee for Diabetes, 2026).

The ADA does recommend GLP-1 and GIP/GLP-1 RAs as the first-choice injectable therapy in type 2 diabetes, ahead of insulin, in people without evidence of insulin deficiency. This is because these incretin agents:

• Offer greater improvements in HbA_1c.
• Induce weight loss, rather than the weight gain seen with insulin.
• Carry a lower risk of hypoglycaemia and do not require intensive glucose monitoring.
• Are available as once-weekly injections.
• Have an easier titration regimen.
• Potentially offer cardiorenal benefits.

Section 17 – Starting a basal insulin: initial dosing and choice of agent

• Initial dose of basal insulin: 0.1–0.2 units/kg/day, or 10 units/day.
• Use human NPH insulin (e.g. Humulin® I, Insulatard®) or a long-acting basal insulin analogue such as Lantus® (insulin glargine), Semglee® (biosimilar insulin glargine), Abasaglar® (biosimilar insulin glargine), Tresiba® (insulin degludec) or Toujeo® (300 units/mL insulin glargine).
• Long-acting basal insulin analogues carry a lower risk of hypoglycaemia (including nocturnal hypoglycaemia) than human NPH insulin (Semlitsch et al, 2020)