Type 2 diabetes management toolbox: from lifestyle to insulin

Diabetes management essentials

Type 2 diabetes continues to be a significant health issue in New Zealand. Overall, 5% of the adult population has been diagnosed with type 2 diabetes, with the highest rates among people of Māori, Pacific and South-Asian ethnicity, people who are socioeconomically disadvantaged and older people (aged > 65 years).^{1, 2} The prevalence is also increasing in younger people.

Optimal management, including lifestyle approaches (i.e. a healthy diet and exercise), diabetes education and support, and pharmacological treatments, are key to reducing the risk of long-term diabetes complications and help people with type 2 diabetes to live well.

For further information on diabetes in young people, see: “A rising tide of type 2 diabetes in younger people: what can primary care do?”

Management begins with lifestyle

A healthy lifestyle is the foundation of treatment for all people with type 2 diabetes. Cardiovascular disease (CVD) is the greatest cause of early mortality and morbidity in people with type 2 diabetes, and appropriate nutrition and physical activity interventions simultaneously address cardiovascular risk factors and levels of glycaemia.³

The first step following diagnosis of type 2 diabetes should be to try to induce remission through lifestyle interventions to achieve weight loss (see below) and metformin treatment (see: “Pharmacological treatment to reduce HbA_1c levels”).^{3, 4} Additional pharmacological treatments may be required to reduce HbA_1c levels, but these may be able to be de-escalated or discontinued in some patients who make significant changes to their lifestyle.⁴ Weight loss should be encouraged at any stage of type 2 diabetes to induce remission, slow progression, step down treatment intensity or delay the need to escalate treatment.

Key lifestyle goals for patients to aim for include:³

• At least 150 minutes per week of moderate intensity exercise – this may not be immediately achievable, but patients should have a plan to increase their level of physical activity to reach this goal
• Weight loss (5 – 10% of total body weight) in those who are overweight^* – various dietary approaches are available; consider patient preference, tolerance, nutritional requirements, co-morbidities, cultural suitability and cost
• Eating foods with a high fibre content, such as fruits, vegetables and whole grains, and avoiding sugar-sweetened beverages or foods with added sugars

^*BMI > 30 kg/m² or BMI > 25 kg/m² with waist circumference > 88 cm in females or > 102 cm in males³

For further information on weight loss in type 2 diabetes management, see: “Weight loss for the prevention and treatment of type 2 diabetes”

Diabetes education and support is a critical aspect of lifestyle management. The goal is to enable the patient to take an active role in their care without making them feel judged or to blame for having diabetes. Providing patients with an explanation of what goes wrong at a biological level with an increasing duration of type 2 diabetes can help them understand the need for making changes to their lifestyle and the role of medicines in diabetes management.

For example, explain to patients that their body is not responding to insulin as well as someone without diabetes, and that in turn the pancreas increases insulin levels in order to decrease blood glucose levels. However, this cannot be maintained long-term and for many people additional oral medicines or injecting dulaglutide or insulin becomes necessary as time goes on. Losing weight, exercising and eating well can improve the body’s sensitivity to insulin and therefore this is something that the patient can do to reduce their need for medicines. In some patients, significant sustained lifestyle changes can normalise HbA_1c levels and medicines may no longer be required.

Connect patients to services that can assist with lifestyle changes and provide support. This could include referring patients to a dietitian, providing them with a Green Prescription to connect with a Green Prescription support person, or making patients aware of programmes offered by a local PHO, DHB (e.g. DESMOND) or Māori health provider. Diabetes New Zealand has branches throughout the country that provide a variety of services. For further information, see: www.diabetes.org.nz

Pharmacological treatment to reduce HbA_1c levels

Prescribing medicines to reduce HbA_1c levels in patients with type 2 diabetes is a balancing act, which aims to reduce HbA_1c levels as far as possible without causing harm.⁵ Hypoglycaemia is the main limiting adverse effect associated with reducing HbA_1c levels, and it can carry substantial risks, particularly in patients who are frail. Hypoglycaemia is associated with an increased risk of falls and cognitive impairment, and may increase the risk of mortality.⁵

Choosing a target: the first step

A HbA_1c target should be individualised and determined by factors such as the patient’s co-morbidities, potential duration of the patient’s exposure to hyperglycaemia, history of hypoglycaemia and overall health status (Table 1).^{3, 6}

Reaching and maintaining target HbA_1c levels can reduce a patient’s risk of microvascular complications, e.g. retinopathy, nephropathy, and neuropathy.^{3, 6} Reducing HbA_1c in patients with particularly high levels, e.g. > 80 mmol/mol, to a more moderate level, e.g. < 65 mmol/mol, is thought to offer the greatest reductions in risk of microvascular complications.⁶ Aiming for a very low target is not always best if the risks associated with reducing HbA_1c levels, e.g. hypoglycaemia, outweigh the benefits.^{3, 6} Reducing HbA_1c is also part of the multi-factorial risk reduction strategy, which includes increasing physical activity, smoking cessation and managing hypertension and dyslipidaemia, to reduce macrovascular complications of diabetes.⁷

For further discussion on adjusting HbA_1c treatment targets, see: bpac.org.nz/2019/diabetes-elderly.aspx

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Table 1: Patient characteristics to consider when selecting a HbA_1c target^3,5,6

Prescribing glucose-lowering medicines: choosing the right tools for the job

The pharmacological management of type 2 diabetes typically follows a stepwise progression with lifestyle interventions, i.e. diet and exercise to induce weight loss, reinforced at each intensification step (Figure 1). The intensity of pharmacological treatments required to reduce and maintain HbA_1c at target levels varies greatly between patients and also depends on the extent of lifestyle changes, the length of time they have had diabetes and their particular circumstances and preferences.⁵ For patients with high HbA_1c levels (> 64 mmol/mol) at diagnosis, initiating two medicines is recommended (e.g. metformin and vildagliptin).³ For patients with very high HbA_1c levels, e.g. > 80 – 90 mmol/mol, or significant symptoms of hyperglycaemia at diagnosis, initiation of insulin (in addition to metformin) is recommended.³ It is often possible to reduce insulin or remove it from the regimen once HbA_1c stabilises.⁸

Figure 1: Optimising the management of HbA_1c levels with glucose-lowering medicines in patients with type 2 diabetes^{3, 5}

Step 1: Metformin is the initial choice of oral medicine for most patients

Metformin is recommended as the initial pharmacological approach for patients with type 2 diabetes, as it reduces HbA_1c levels, decreases cardiovascular disease risk independent of glycaemic control, may assist with weight loss and has a low risk of hypoglycaemia (Figure 1 and Table 2).³ Initiate metformin at a low dose, e.g. 500 mg once daily, and gradually increase the dose over the following weeks to a maximum of 1.5 – 2 g daily, in divided doses, as tolerated.⁹ A higher maximum dose of 3 g, daily may be prescribed for patients with creatinine clearance > 120 mL/min.^{9 *}

^*While in many cases eGFR will be sufficient to estimate renal function in patients taking metformin, the NZF recommends using the Cockcroft-Gault equation for a more accurate calculation of creatinine clearance, which may be particularly useful in people with more severe renal impairment.⁹ A calculator is available here: www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation

Step 2: Prescribing combination treatment

If patients require intensification of pharmacological management, the recommended next step is to combine metformin with another non-insulin glucose-lowering medicine (or use two of these medicines if metformin is contraindicated or not tolerated). Funded options include:^{3, 9}

• A sodium-glucose co-transporter 2 (SGLT-2) inhibitor: empagliflozin^{* †}
• A glucagon-like peptide (GLP-1) receptor agonist: dulaglutide^†
• A dipeptidyl-peptidase 4 (DPP-4) inhibitor: vildagliptin^*
• A sulfonylurea: either gliclazide or glipizide^**
• A thiazolidinedione: pioglitazone

^*Available in a single formulation and in combination with metformin

^†Special Authority criteria apply. For further information see: “New diabetes medicines funded: empagliflozin and dulaglutide”

**Glibenclamide is another subsidised sulfonylurea, however, prescribing glibenclamide is generally not recommended as it is associated with a higher risk of hypoglycaemia than other sulfonylureas⁵

When prescribed in combination with metformin there are no clinically meaningful differences in the extent of HbA_1c lowering between the non-insulin glucose-lowering medicines; adding one of these medicines to metformin treatment generally reduces HbA_1c by approximately 8 – 11 mmol/mol.^{8, 10} There are, however, other reasons for selecting one medicine over another (see: “Which medicine to choose?”).

Acarbose is another fully funded glucose-lowering medicine which could be added to metformin treatment if other medicines are not tolerated, however, available data suggest it is less effective at lowering HbA_1c levels when added to metformin than the medicines above.¹¹ Adverse effects include bloating, flatulence, diarrhoea and, rarely, deranged liver function tests.³

Which medicine to choose?

Clinicians and patients can jointly decide which of the above options to add to treatment after considering any contraindications, co-morbidities, risk of hypoglycaemia, effects on weight, medicines interactions, adverse effects and eligibility for funding (Table 2).

Empagliflozin or dulaglutide are preferred for people with established or at high risk of CVD, or with heart failure or diabetic kidney disease, regardless of their HbA_1c levels; currently only patients with HbA_1c levels > 53 mmol/mol who are at high risk of CVD or renal complications are eligible for funded treatment.³ A combination metformin + empagliflozin formulation is available fully funded with Special Authority.

For further information on prescribing these medicines, see: “New diabetes medicines funded: empagliflozin and dulaglutide”

Vildagliptin is preferred for patients who are not eligible for funded empagliflozin or dulaglutide treatment.³ A combination formulation of metformin + vildagliptin is available fully funded without restriction.

Some guidelines favour the addition of vildagliptin or a sulfonylurea instead of pioglitazone due to potential adverse effects associated with pioglitazone.⁵ Vildagliptin or pioglitazone may be preferred over a sulfonylurea if patients have problems with hypoglycaemia.

N.B. Prior to initiating vildagliptin, request baseline liver function tests (Table 2).³

For further information on prescribing vildagliptin, see “Prescribing vildagliptin for type 2 diabetes”

Escalating beyond dual treatment

Options for treatment intensification for patients who have HbA_1c levels above the desired target despite optimal use of two non-insulin medicines and lifestyle approaches are:

• Initiating a third non-insulin medicine (either an oral medicine or an injectable GLP-1 receptor agonist [i.e. dulaglutide])
• Initiating insulin (i.e. Step 3 – see below)

Take into account the patient’s other prescribed medicines, which will often include an angiotensin-converting enzyme (ACE) inhibitor, statin, antihypertensives and aspirin, and consider whether triple oral therapy is likely to create difficulties with adherence.

There is very little clinical trial evidence to guide choice of which third non-insulin medicine to add. In general, the incremental effect of adding a third oral medicine is likely to be less than when these medicines are used alone or in dual treatment combinations.⁸

In international guidelines, adding a GLP-1 receptor agonist is the preferred next step for patients requiring escalation to injectable treatment, however, not all patients will be eligible for funded treatment in New Zealand.^{3, 8} Initiating dulaglutide may be more acceptable to patients than insulin. While both are injectable treatments, dulaglutide is administered once weekly and self-monitoring of blood glucose levels is not necessary (unless their regimen includes a sulfonylurea).

Combination SGLT-2 inhibitor and GLP-1 receptor agonist treatment, in addition to metformin, is the recommended next step for people at high risk of cardiovascular or renal complications who were previously treated with just one of these medicine classes, however, dual treatment is not currently funded.³

Step 3: Insulin

Discuss insulin initiation with patients who have HbA_1c levels above the desired target despite optimal use of two oral medicines and lifestyle approaches, or where a rapid escalation of pharmacological treatment is required because of high HbA_1c levels. Insulin has the largest effect on reducing HbA_1c levels of all glucose-lowering medicines, however, it is also associated with greater weight gain and a higher risk of hypoglycaemia than other glucose-lowering medicines (Table 2).⁸ Weight gain typically plateaus after the first one to three years of treatment and is dose-dependent.^{19, 20}

Reassurance and advice is often required when discussing the possibility of initiating insulin with patients to ensure that any anxieties about insulin are addressed, e.g. feeling that it signifies an escalation in the seriousness of their condition, being worried or embarrassed about self-injection, needles or calculating doses, and fear of weight gain or hypoglycaemia. After discussing options some patients may wish to trial more intensive changes to their dietary or physical activity approaches instead of initiating insulin. If this is the case, agree to a time frame for review to ensure that insulin treatment is not unduly delayed.

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Table 2: Funded glucose-lowering medicines and factors to consider when prescribing.^3,9

^* While in many cases eGFR will be sufficient to estimate renal function in patients taking metformin, the NZF recommends using the Cockcroft-Gault equation for a more accurate calculation of creatinine clearance, which may be particularly useful in people with more severe renal impairment.⁹ A calculator is available here: www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation

^† The combination vildagliptin + metformin formulation is not recommended in patients with eGFR < 60 mL/min/1.73m²; prescribing metformin and vildagliptin in separate tablets may be preferable to allow for an appropriate reduced dose of metformin.

Summary of key points for initiating patients with type 2 diabetes on insulin:³

A detailed discussion on initiating and up-titrating insulin, including the different regimens, insulins and devices, is available in: “Initiating insulin for people with type 2 diabetes“

• Most patients are initiated on once-daily basal insulin, injected at night; isophane insulin (an intermediate-acting insulin) is an appropriate choice for most patients
• A weight-based approach is recommended to determine the initial basal insulin dose:
  • 0.1 units/kg daily if at least one of:
    • HbA_1c < 64 mmol/mol
    • BMI < 18 kg/m² (less likely to have type 2 diabetes)
    • Older (e.g. aged > 65 years) or frailty
    • Renal or liver failure
  • 0.2 units/kg daily if HbA_1c > 64 mmol/mol and BMI > 18 kg/m²
• Patients initiating basal insulin should begin self-monitoring blood glucose levels; a once daily measurement before breakfast (if insulin is taken at night) is sufficient; the aim of treatment is to achieve blood glucose levels between 6 – 8 mmol/L
• Patients will need to titrate the insulin dose upwards from this starting point based on their fasting blood glucose levels
• Patients who continue to have elevated HbA_1c levels while using a basal insulin regimen may require intensification of insulin treatment. This could include switching to a biphasic insulin formulation, which includes long-acting and short-acting insulins in a premixed solution, or continuing with a basal insulin and adding a short-acting insulin at mealtimes.
• More frequent blood glucose monitoring is advised when introducing other insulin regimens, e.g. adding a fast-acting insulin at mealtimes. Monitoring before meals and before bed is useful.
• Ask patients to check their blood glucose levels if they experience symptoms consistent with hypoglycaemia. If an obvious cause is not apparent, e.g. missed meals, changes to carbohydrate intake or exercise regimen, patients should reduce their insulin dose by 10 – 20%.

Patient information on recognising and responding to hypoglycaemia is available at: www.healthnavigator.org.nz/health-a-z/l/low-blood-glucose

Continuing other medicines

Metformin is usually continued when insulin is started as it can result in less weight gain and lower doses of insulin being required to meet HbA_1c targets.²¹

Empagliflozin is usually continued when insulin is initiated; combining SGLT-2 inhibitor and insulin treatment can result in less weight gain and greater reduction in HbA_1c levels without increasing the risk of hypoglycaemia.²² Empagliflozin also provides cardiovascular and renal benefits independent of its actions on glycaemia.³

Dulaglutide is usually continued when insulin is initiated; combining GLP-1 receptor agonist and insulin treatment can result in less weight gain and greater reduction in HbA_1c levels without increasing the risk of hypoglycaemia.²³ Dulaglutide also provides cardiovascular and renal benefits independent of its actions on glycaemia.³

Vildagliptin may be continued when insulin is initiated, but in practice is often withdrawn to simplify the regimen. The formulation of vildagliptin + metformin is also approved for use in combination with insulin.

Sulfonylureas may be continued if patients are using basal insulin as a lower dose of insulin is required to meet the HbA_1c target.³ However, there is an increased risk of hypoglycaemia when these medicines are used in combination.³ Sulfonylureas are titrated down and withdrawn if treatment with a short-acting insulin is initiated.²¹

Pioglitazone is typically discontinued when insulin is initiated as combined use increases the risk of oedema.²⁴

Regularly revise treatment approaches and goals

Most people with type 2 diabetes will have it for the rest of their lives. Regular review of treatment is necessary to optimise individual goals of treatment and ensure medicine regimens remain appropriate.

Measuring HbA_1c levels at three to six month intervals is recommended to determine the effect of lifestyle and pharmacological approaches (Figure 1).³ Treatment can then be optimised by checking and reinforcing lifestyle approaches, adjusting doses, adding or withdrawing medicines, or adjusting HbA_1c targets, as appropriate. An annual check is sufficient for patients with stable, well controlled HbA_1c levels.

Discuss diet and physical activity. For all patients, sustaining lifestyle changes and maintaining weight loss is required for long term improvements in HbA_1c levels and cardiovascular risk factors. Achieving this can be difficult; offer regular encouragement and assess barriers the patient is experiencing. Monitor body weight and ideally waist circumference annually.³

For further information on lifestyle management, see: “Weight loss for the prevention and treatment of type 2 diabetes”

Discuss medicine use and adverse effects. Ask patients about adverse effects or any difficulties they are having with their prescribed medicines which could contribute to reduced adherence.

Consider the simplicity of the patient’s medicine regimen,including medicines prescribed for co-morbidities, and whether any changes are possible to improve adherence.⁵

Ask about hypoglycaemia if the patient is taking a sulfonylurea or insulin. If patients have symptoms of hypoglycaemia, discuss when they occurred, and the circumstances involved, e.g. a missed meal, acute illness. Ensure the patient is aware of symptoms of nocturnal hypoglycaemia, such as nightmares or disturbed sleep, being particularly hungry in the morning or waking with wet sheets due to sweating.³ Problems with hypoglycaemia should prompt consideration of reducing doses of medicines, changing medicines or adjusting HbA_1c targets.

Review management of cardiovascular and renal risk factors: Annual review of cardiovascular and renal risk factors, including blood pressure and lipid levels, albumin:creatinine ratio and eGFR, is recommended.³ In addition, an annual foot check and recall for retinopathy screening at least every two years is recommended. Many PHOs have funding for this review. N.B. More frequent review may be indicated depending on the patient’s risk factors.

A calculator to assess CVD risk in people with type 2 diabetes is available here: www.nzssd.org.nz/calculators/calculator/1/cvd-risk-assessment/

For further information on an annual diabetes review, see: “The annual diabetes review: screening, monitoring and managing complications”

Patient information

• Patient information on type 2 diabetes, the importance of diet and physical activity, and recognising and responding to hypoglycaemia is available from:
  • Diabetes New Zealand: www.diabetes.org.nz
  • Ministry of Health “Keeping well with diabetes” booklet, available in English, Māori, Cook Islands Māori, Samoan, Tongan and Niuean: www.healthed.govt.nz/search?topic%5B0%5D=3&type=resource&mode=picture-view
  • Health Navigator: https://www.healthnavigator.org.nz/health-a-z/d/diabetes-type-2/
• A guide to initiating insulin for patients with type 2 diabetes, produced by the Waitematā District Health Board, is available in various languages: http://www.saferx.co.nz/patient-guides/