Initiating non-insulin-based treatment in adults with type 2 diabetes: a practical guide
Intended for healthcare professionals

Primary Health Care

CPD    

Initiating non-insulin-based treatment in adults with type 2 diabetes: a practical guide

Martha Stewart Diabetes specialist nurse, University Hospitals Birmingham NHS Foundation Trust and deputy programme lead (MSc in advancing diabetes care), Birmingham City University, Birmingham, England
Share to Facebook Share to X Share to Whatsapp Share to Email More...

Why you should read this article:

  • • To reinforce your knowledge of the guidance on non-insulin-based treatment for type 2 diabetes

  • • To enhance your understanding of the mode of action, benefits and risks of diabetes medicines

  • • To contribute towards revalidation as part of your 35 hours of CPD (UK readers)

  • • To contribute towards your professional development and local registration renewal requirements (non-UK readers)

Type 2 diabetes is characterised by progressive pancreatic beta cell dysfunction, overproduction of glucose by the liver and insulin resistance. Furthermore, it can lead to microvascular and macrovascular complications. In addition to lifestyle changes, the management of type 2 diabetes usually involves medicines that address the characteristics and risks specific to the condition. As part of the pharmacological treatment of type 2 diabetes, patients are often prescribed, beyond insulin, one or more non-insulin-based medicines. This article discusses the non-insulin-based treatment options for type 2 diabetes and provides nurses with practical advice and useful resources to help them support their patients.

Primary Health Care. doi: 10.7748/phc.2024.e1828

Peer review

This article has been subject to external double-blind peer review and checked for plagiarism using automated software

@MChivima

Correspondence

Martha.Stewart@bcu.ac.uk

Conflict of interest

None declared

Stewart M (2024) Initiating non-insulin-based treatment in adults with type 2 diabetes: a practical guide. Primary Health Care. doi: 10.7748/phc.2024.e1828

Published online: 18 September 2024

Keywords :

blood glucose - clinical - community - diabetes - diabetic ketoacidosis - general practice - glycaemic control - hyperglycaemia - hypoglycaemia - medicines - practice nurses - prescribing - type 2 diabetes

Download PDF
Download Citation
Article metrics
Multiple-choice quiz

Aims and intended learning outcomes

As the prevalence of type 2 diabetes continues to rise (Hossain et al 2024), nurses working in primary care have a central role in supporting patients with the condition. The first point of contact of people with type 2 diabetes is often a general practice nurse. Furthermore, community and general practice nurses are often responsible for monitoring adherence to treatment, the effectiveness of treatment and potential side effects. They need to be familiar with diabetes treatment guidelines so that they can prescribe appropriately – if they are prescribers – and inform, advise and educate patients about their medicines. The aim of this article is to support nurses working in primary care to initiate non-insulin-based treatment in adults with type 2 diabetes and assist patients to understand their treatment and adhere to it. After reading this article and completing the time out activities you should be able to:

  • • Explain when and how to use the different non-insulin-based medicines that may be needed for managing type 2 diabetes.

  • • Describe the mode of action, benefits and risks of the different non-insulin-based medicines.

  • • Provide patients with appropriate information, advice and education about their non-insulin-based medicines.

Introduction

The management of type 2 diabetes involves a combination of lifestyle measures and pharmacological treatment. Type 2 diabetes is characterised by a progressive decline in the production of insulin by pancreatic beta cells, which means that many patients will require insulin therapy as their condition progresses (Home et al 2014, Tahrani et al 2016).

Beyond insulin, treatment regimens for type 2 diabetes often encompass non-insulin-based medicines. Insulin therapy for type 2 diabetes is the focus of a previous article by the author (Stewart 2024). This present article discusses the non-insulin-based treatment options for type 2 diabetes and provides nurses with practical advice and useful resources to help them support their patients.

Key points

  • • In 2022, the National Institute for Health and Care Excellence updated its guideline on type 2 diabetes in adults

  • • Beyond lifestyle measures and insulin, the management of type 2 diabetes often involves non-insulin-based medicines

  • • Medicines used for managing type 2 diabetes vary in their mode of action, benefits and risks

  • • Classes of medicines used in type 2 diabetes encompass biguanides, sulfonylureas, thiazolidinediones, sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors

  • • A thorough understanding of non-insulin-based medicines is important to be able to provide patients with education and advice

Characteristics of type 2 diabetes

Type 2 diabetes is a complex metabolic condition caused by defective insulin secretion, defective insulin action or both. It is characterised by progressive pancreatic beta cell dysfunction, leading to reduced insulin production (UK Prospective Diabetes Study (UKPDS) Group 1998, Kahn et al 2014). The loss of pancreatic beta cell function means patients may need to take medicines that stimulate insulin production (UKPDS Group 1998, Wysham and Shubrook 2020).

Another characteristic of type 2 diabetes is overproduction of glucose by the liver, even during normoglycaemia (Rines et al 2016). Incretin hormones secreted by the gut have an important role in glucose regulation. In type 2 diabetes, there is a deficiency of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), resulting in hyperglycaemia (Nauck and Müller 2023). People with type 2 diabetes may therefore need to take medicines that enhance the action of endogenous incretin hormones (Rines et al 2016).

A further characteristic of type 2 diabetes is insulin resistance, defined as reduced responsiveness of insulin-targeting tissues to physiological levels of insulin (Lee et al 2022), which may require patients to take medicines that increase the cells’ sensitivity to insulin. Overweight is a major risk factor for insulin resistance (Wondmkun 2020).

If inadequately managed, type 2 diabetes can lead to microvascular and macrovascular complications, which are major contributors to patient morbidity and mortality (World Health Organization 2019). People with type 2 diabetes are at high risk of cardiovascular and renal complications (Martín-Timón et al 2014). In addition to lifestyle changes, the management of type 2 diabetes therefore often involves medicines that address these risks.

Guidance on non-insulin-based medicines for type 2 diabetes

The complexity of type 2 diabetes has prompted significant interest in developing new pharmacological treatments (Dahlén et al 2022). In 2022, the National Institute for Health and Care Excellence (NICE) (2022) updated its guideline on the management of type 2 diabetes in adults to reflect findings from recent trials, particularly regarding the cardiovascular and renal benefits of certain medicines. This first section of the article describes NICE’s (2022) recommendations regarding first-, second- and third-line treatment aimed at reaching a glycated haemoglobin (HbA1c) level of 48mmol/mol. NICE (2022) emphasises that the HbA1c target should be individualised and recommends aiming for an HbA1c level of 53mmol/mol in older people and those at risk of hypoglycaemia.

Time Out 1

Review your local diabetes treatment guidelines. Do they reflect the latest NICE (2022) guidance, particularly regarding sodium glucose cotransporter-2 (SGLT-2) inhibitors? If so, how has this altered care provision? If not, what can you do to ensure they are updated?

First-line treatment

As first-line treatment, NICE (2022) recommends promoting lifestyle changes – eating a healthy diet and engaging in physical activity. If the target HbA1c level is not achieved after three months of lifestyle changes, metformin hydrochloride, unless not tolerated or contraindicated, is the first-line treatment of choice. If the patient experiences gastrointestinal side effects from the standard metformin formulation, they should be offered a slow-release formulation; if the slow-release formulation is not tolerated, alternatives are a dipeptidyl peptidase 4 (DPP-4) inhibitor, a sulfonylurea or pioglitazone (NICE 2022).

NICE (2022) also recommends that people with type 2 diabetes who have, or are at high risk of, cardiovascular disease take a sodium glucose cotransporter-2 (SGLT-2) inhibitor, which clinical trials have shown to offer cardio-renal protection (Xiang et al 2021). To distinguish between potential side effects, metformin should be initiated first, followed by a SGLT-2 inhibitor. There should be no delay in starting treatment with an SGLT-2 inhibitor once the tolerability of metformin has been determined (NICE 2022).

Second-line treatment

If the patient’s HbA1c level remains above target despite lifestyle changes and monotherapy with metformin (or an alternative), complemented by an SGLT-2 inhibitor where needed, second-line treatment is required. Second-line treatment consists in adding a DPP-4 inhibitor, a sulfonylurea, pioglitazone or an SGLT-2 inhibitor to the treatment regimen, according to which of these medicines have or have not already been introduced (NICE 2022).

Third-line treatment

If the target HbA1c level is still not achieved, there is scope to add either insulin or a second or third medicine, or to replace one of the existing medicines by a glucagon-like peptide-1(GLP-1) receptor agonist if the patient is eligible for it. Eligibility criteria for GLP-1 receptor agonists are (NICE 2022):

  • • Patients with a body mass index (BMI) ≤35kg/m2 for whom insulin therapy would have significant occupational implications.

  • • Patients in whom weight loss would be beneficial in terms of managing other significant obesity-related comorbidities.

  • • Patients with a BMI ≥35kg/m2 and specific psychological or other medical issues associated with obesity.

When determining eligibility for treatment with a GLP-1 receptor agonist, BMI thresholds need to be adjusted for people from certain minority ethnic backgrounds. People from a South Asian, Chinese, other Asian, Middle Eastern, black African or African-Caribbean background are prone to central adiposity and their cardiometabolic risk increases at a lower BMI than white people; however, the thresholds for healthy weight, overweight and obesity have been determined based on data gained mostly from white populations (Caleyachetty et al 2021, NICE 2023a). NICE (2023a) recommends that, for people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean backgrounds, the BMI thresholds for obesity class 2 and obesity class 3 are reduced by 2.5kg/m2.

Time Out 2

Consider how you could turn Table 1 into a practical resource for you and your colleagues. What would be the best format and medium? How would you go about it? Who would you need to speak to? What resources would you need?

Overview of non-insulin-based medicines used in the management of type 2 diabetes

• Muscle and adipose tissue

• Liver

• Nausea, vomiting, diarrhoea

• Lactic acidosis

• Muscle and adipose tissue

• Liver

• Vulval candidiasis

• Dehydration

• Euglycaemic diabetic ketoacidosis

• Enhanced insulin production

• Suppressed glucagon secretion

• Slowing of gastric emptying

• Reduced appetite and food intake

• Gastrointestinal system

• Pancreas

• Liver

• Nausea, vomiting, diarrhoea

• Pancreatitis

• Transient worsening of active retinopathy

• Gastrointestinal system

• Pancreas

• Liver

• Nausea, vomiting, diarrhoea

• Pancreatitis

(Adapted from American Diabetes Association 2022, National Institute for Health and Care Excellence 2022, GPnotebook 2023, Joint Formulary Committee 2024)

Non-insulin-based medicines for type 2 diabetes

Table 1 provides an overview of the different non-insulin-based medicines used in the management of type 2 diabetes.

Biguanides

Metformin – the only medicine in the biguanide class – works by enhancing the sensitivity of muscle cells and adipose tissue to the action of insulin, allowing glucose to enter the cells and therefore lowering blood glucose levels (Joint Formulary Committee 2024). Metformin offers cardiovascular benefits (UKPDS Group 1998, Bu et al 2022), which is why it is the medicine of choice for first-line treatment. Additionally, metformin does not carry a risk of hypoglycaemia, since it does not target pancreatic beta cells (Electronic Medicines Compendium (EMC) 2022).

Common side effects of immediate-release metformin are gastrointestinal symptoms, including nausea, vomiting, abdominal pain and diarrhoea (Joint Formulary Committee 2024). Nurses need to advise patients to always take metformin with food to reduce the incidence of gastrointestinal side effects. If these persist, they are usually resolved by either gradual titration every ten to 15 days (Joint Formulary Committee 2024) or conversion to a modified-release formulation (Aggarwal et al 2018). Metformin is cleared via the kidneys and may accumulate when there is renal dysfunction, potentially causing lactic acidosis, so it is contraindicated in patients with an estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2 (Joint Formulary Committee 2024).

Patients must be given information about the side effects of metformin and advised to contact their surgery to discuss potential side effects. Patients’ renal function must be monitored and the metformin dose reduced if their eGFR decreases to <60mL/min/1.73m2, and reduced again if their eGFR decreases to <45mL/min/1.73m2 (Joint Formulary Committee 2024).

Time Out 3

One of your patients with type 2 diabetes is taking a sulfonylurea and metformin. She tells you she is having dizzy spells several times a week, but her HbA1c level is the closest to target it has ever been. What advice would you give her? What would your action plan be?

Sulfonylureas

Sulfonylureas work by binding to sulfonylurea receptors on pancreatic beta cells, causing an increase in plasma insulin concentration. Therefore, they only work in the early stages of type 2 diabetes when pancreatic beta cell function is not yet too diminished (Sola et al 2015, Dludla et al 2023). Their blood-glucose lowering effect is immediate, with plasma insulin levels reaching maximal concentrations within two to six hours of administration (Mills and Devendra 2015, Joint Formulary Committee 2024).

Type 2 diabetes is characterised by hyperglycaemia and patients who develop symptomatic hyperglycaemia will need to take either insulin or a sulfonylurea (NICE 2022). Furthermore, sulfonylureas are the first-choice oral treatment for corticosteroid-induced hyperglycaemia (Joint British Diabetes Societies for Inpatient Care 2021). For more information on the management of corticosteroid-induced diabetes and hyperglycaemia, see Morris (2022).

Because of the mode of action of sulfonylureas, their most common side effect is hypoglycaemia (Sola et al 2015, Beba et al 2023). Sulfonylureas should be avoided in older people with frailty and renal impairment because of the risk of falls (Sola et al 2015). Another drawback of sulfonylureas is weight gain, likely a result of increased appetite caused by efforts to avoid hypoglycaemia (Schwartz and Herman 2015). This can usually be mitigated by the concurrent administration of metformin (Sola et al 2015).

Patients who take a sulfonylurea need to be supplied with a blood glucose monitor and shown how to use it, to be advised on what blood glucose levels to aim for, and to receive education on the recognition, treatment and prevention of hypoglycaemia (NICE 2022). Regular reviews are important to reduce the harm caused by recurrent episodes of hypoglycaemia, so patients should be advised to inform their nurse if they experience ‘hypos’. If they drive, patients need to know the rules about informing the Driver and Vehicle Licensing Agency (DVLA) and how to test their blood glucose level before driving. See under ‘Further resources’ for information for healthcare professionals and patients on the recognition, management and prevention of hypoglycaemia.

Further Resources

TREND Diabetes – information for healthcare professionals on hypoglycaemia

TREND Diabetes – patient resource about hypoglycaemia

TREND Diabetes – patient resource about driving

Thiazolidinediones

Pioglitazone – the only medicine in the thiazolidinedione class – has been shown to reduce hepatic glucose production and increase insulin sensitivity (Soccio et al 2014). It does not target the pancreas and therefore does not cause hypoglycaemia (EMC 2020).

Before treatment with pioglitazone is started, patients’ suitability for the medicine needs to be established and their risk factors for bladder cancer assessed. This is because a randomised controlled trial showed an imbalance in the number of cases of bladder cancer with pioglitazone (Dormandy et al 2005). There is a small increased risk of bladder cancer associated with pioglitazone, so it should not be used in patients with active bladder cancer or a history of bladder cancer, and it should be used with caution in older people, since the risk of bladder cancer increases with age (Joint Formulary Committee 2024).

Pioglitazone is associated with weight gain, which may be due to fat accumulation. It may also be associated with fluid retention, which is a potential symptom of cardiac failure. Patients’ weight should therefore be closely monitored (EMC 2020).

Patients should be advised to seek immediate medical attention if they experience side effects of pioglitazone, notably (EMC 2020):

  • • Unusual shortness of breath, rapid increase in weight and localised swelling (oedema), which can indicate heart failure.

  • • Blood in urine, pain when urinating and sudden need to urinate, which can indicate bladder cancer.

  • • Broken bones.

  • • Blurred vision or worsening of existing blurred vision, which can be caused by swelling (or fluid) at the back of the eye.

Sodium glucose cotransporter-2 inhibitors

SGLT-2 inhibitors work by inhibiting the sodium-glucose transport protein SGLT-2 in the proximal convoluted tubules in the kidneys to reduce glucose reabsorption and encourage glucose excretion (Joint Formulary Committee 2024). They have been shown to improve cardiovascular outcomes in adults with type 2 diabetes and chronic heart failure or established atherosclerotic cardiovascular disease (NICE 2023b). They also reduce the risk of chronic kidney disease (CKD) progression and mortality and the risk of cardiovascular events in adults with type 2 diabetes and CKD (NICE 2022). The use of SGLT-2 inhibitors induces a weight loss of 2kg-4kg after six-to-12 months of treatment and does not cause hypoglycaemia (Fonseca-Correa and Correa-Rotter 2021).

The disadvantages of SGLT-2 inhibitors include an increased risk of genital infections due to the passing of glucose-containing urine (Fonseca-Correa and Correa-Rotter 2021). The use of SGLT-2 inhibitors has been associated with Fournier’s gangrene, a rare but potentially life-threatening infection affecting the genital or perineal area (Joint Formulary Committee 2024). Patients therefore need to be advised to maintain adequate genital hygiene.

If taken during acute illness, SGLT-2 inhibitors can lead to dehydration and acute kidney injury (AKI), increasing the risk of euglycaemic diabetic ketoacidosis (EDKA) (Pfützner et al 2017, Joint Formulary Committee 2024). EDKA refers to diabetic ketoacidosis (DKA) occurring with normal or close-to-normal blood glucose levels (Chow et al 2023). Because of the risk of EDKA, patients should be advised to avoid a ketogenic or very low carbohydrate diet during acute illness, since such diets increase the risk of ketone formation and dehydration (Fukuyama et al 2020, Musso et al 2020, Diabetes UK 2021). Before prescribing an SGLT-2 inhibitor, it is important to assess the patient’s risk of DKA, determine whether they have previously had DKA, check whether they are unwell with intercurrent illness and ascertain whether they are following a ketogenic or very low carbohydrate diet. Patients who use a blood glucose meter must be made aware that their blood glucose levels will not necessarily be elevated if they develop EDKA. Furthermore, patients need to be educated about the signs and symptoms of DKA (Box 2).

Box 2. Signs and symptoms of diabetic ketoacidosis

  • • Excessive thirst

  • • Polyuria

  • • Dehydration

  • • Shortness of breath and laboured breathing

  • • Abdominal pain

  • • Leg cramps

  • • Nausea and vomiting

  • • Loss of appetite

  • • Mental confusion and drowsiness

  • • Lethargy

  • • Fatigue

(Adapted from Down 2020)

Preventive foot care, which is important for all patients with diabetes mellitus, is a special consideration for patients taking SGLT-2 inhibitors. This is because the SGLT-2 inhibitor canagliflozin – and possibly the other medicines in that class – may increase the risk of lower limb amputation (mainly toes) in patients with type 2 diabetes (Neal et al 2017, European Medicines Agency 2017, Medicines and Healthcare products Regulatory Agency (MHRA) 2017, Joint Formulary Committee 2024). Patients must be advised to stay well hydrated, carry out routine preventive foot care and seek medical advice promptly if they develop skin ulceration, discolouration or new pain or tenderness in their feet. All patients will need to be monitored for signs and symptoms of water or salt loss, in particular those with risk factors for amputation – such as previous amputations, existing peripheral vascular disease or existing neuropathy. Canagliflozin may need to be stopped in case of significant lower limb complication, such as skin ulcer, osteomyelitis or gangrene (MHRA 2017, Joint Formulary Committee 2024).

Time Out 4

How well do you know the modes of action of SGLT-2 inhibitors and GLP-1 receptor agonists? Would you know how to choose one against the other? To learn more, watch this video on YouTube: www.youtube.com/watch?v=ewHiXyy0z34

Glucagon-like peptide-1 receptor agonists

GLP-1 receptor agonists work by binding to and activating the GLP-1 receptor in a manner similar to endogenous GLP-1, thereby prolonging the action of endogenous GLP-1 (Elsevier Diabetes 2024), resulting in enhanced insulin secretion, slowing of gastric emptying, suppressed glucagon secretion and reduced appetite and food intake.

The most significant benefit of GLP-1 receptor agonists is weight loss (Uccellatore et al 2015, De Block et al 2022). Gastrointestinal symptoms are their most common side effects and can require the discontinuation of treatment (Elsevier Diabetes 2024, Joint Formulary Committee 2024). The risk of pancreatitis is very small, but the summary of product characteristics warns against using GLP-1 receptor agonists in patients with a history of pancreatitis (EMC 2024). In patients with diabetic retinopathy treated with insulin and the GLP-1 receptor agonist semaglutide, an increased risk of developing complications of diabetic retinopathy has been observed. A rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy (EMC 2024).

Advice for patients includes avoiding oily foods and foods with strong odours and eating little and often. Patients need to be educated about the signs and symptoms of pancreatitis – which include sudden onset of upper abdominal pain that radiates to the back, abdominal pain that worsens after eating, nausea and vomiting – and advised to seek urgent medical attention if they experience any of them (Gorgojo-Martínez et al 2022).

Increased demand for GLP-1 receptor agonists for licensed and off-label indications, including for weight loss, has led to a national shortage (MHRA 2024). The Association of British Clinical Diabetologists and the Primary Care Diabetes Society (2023) have issued guidance on how to manage the shortage.

Dipeptidyl peptidase-4 inhibitors

DPP-4 is an enzyme that deactivates endogenous GLP-1. By inhibiting DPP-4, DPP-4 inhibitors (also called gliptins) enhance the effects of GLP-1. Advantages include that these medicines do not cause weight gain or hypoglycaemia. The DPP-4 inhibitor linagliptin is suitable for use at all stages of renal function and does not require dose adjustment, since it is excreted mainly via the liver, whereas other gliptins are excreted via the kidneys (Joint Formulary Committee 2024).

Patients taking DPP-4 inhibitors can experience nausea and vomiting (Joint Formulary Committee 2024) and they are at risk of developing pancreatitis; acute pancreatitis is associated with significant mortality and morbidity (Singh et al 2013). It has been theorised that incretin-based medicines, because they increase insulin production by the pancreas, can lead to an overactivation of pancreatic cells and therefore to inflammation and damage (Abd El Aziz et al 2020). An increase in hospitalisation rates for heart failure has been observed in clinical trials in patients taking the DPP-4 inhibitor saxagliptin, so saxagliptin is contraindicated in patients with a history of heart failure (Joint Formulary Committee 2024).

GLP-1 receptor agonists and DPP-4 inhibitors have similar mechanisms of action, so there is no clinical benefit in prescribing them concurrently (American Diabetes Association 2022). It is good practice to explain this to patients. Providing an explanation and giving patients an opportunity to ask questions can support adherence to treatment. GLP-1 receptor agonists are usually preferred to DPP-4 inhibitors because they are associated with greater reductions in blood glucose levels and in HbA1c and with greater weight loss (Gilbert and Pratley 2020). However, patients with an aversion to needles and injections may prefer to take a DPP-4 inhibitor, since DPP-4 inhibitors come in the form of oral tablets whereas most GLP-1 receptor agonists are administered via subcutaneous injections.

Further considerations

With many non-insulin-based medicines prescribed for type 2 diabetes, the dose needs to be adjusted according to the patient’s renal function. In certain cases, medicines need to be discontinued or not used at all. TREND Diabetes (2020) provides comprehensive guidance on prescribing for patients with diabetes and renal impairment.

Suboptimal management of diabetes during intercurrent illness can lead to deterioration and the development of serious conditions such as DKA, hyperosmolar hyperglycaemic state or AKI. Any intercurrent illness can cause glucose levels to rise, and continuing or omitting certain medicines can exacerbate patients’ diabetes. Several medicines and classes of medicines should be temporarily stopped when patients have an intercurrent illness, including (Down 2020):

  • • Metformin – there is an increased risk of lactic acidosis if metformin is taken during an acute illness that can lead to dehydration.

  • • SGLT-2 inhibitors – there is an increased risk of euglycaemic DKA if SGLT-2 inhibitors are taken during an acute illness that can lead to dehydration.

For more information on managing diabetes during intercurrent illness, see TREND Diabetes (2022). For more information on sick day rules, see Down (2020).

Time Out 5

Now that you have read the article, are there any changes you and your colleagues should implement in your practice setting? What are these changes and how will you go about making them?

Conclusion

As part of the pharmacological treatment of type 2 diabetes, patients are often prescribed, beyond insulin, one or more non-insulin-based medicines. Classes of medicines used in the management of type 2 diabetes encompass biguanides, sulfonylureas, thiazolidinediones, SGLT-2 inhibitors, GLP-1 receptor agonists and DPP-4 inhibitors. Each has a different mode of action, with potential benefits but also risks and disadvantages. Nurses need a thorough understanding of these medicines so that they can explain to patients the rationale for their treatment regimen, promote adherence to treatment, and educate patients to recognise and act on side effects.

Time Out 6

Undertaking this CPD article can be used as evidence for revalidation, or the equivalent in the country where you work. Now that you have completed it, reflect on your practice in this area and consider writing a reflective account. Guidelines are available at rcni.com/reflective-account

References

  1. Abd El Aziz M, Cahyadi O, Meier JJ et al (2020) Incretin-based glucose-lowering medications and the risk of acute pancreatitis and malignancies: a meta-analysis based on cardiovascular outcomes trials. Diabetes, Obesity and Metabolism. 22, 4, 699-704. doi: 10.1111/dom.13924
    [CROSSREF] [Google Scholar]
  2. Aggarwal N, Singla A, Mathieu C et al (2018) Metformin extended-release versus immediate-release: an international, randomized, double-blind, head-to-head trial in pharmacotherapy-naïve patients with type 2 diabetes. Diabetes, Obesity and Metabolism. 20, 2, 463-467. doi: 10.1111/dom.13104
    [CROSSREF] [Google Scholar]
  3. American Diabetes Association (2022) Standards of Medical Care in Diabetes – 2022 abridged for primary care providers. Clinical Diabetes. 40, 1, 10-38. doi: 10.2337/cd22-as01
    [CROSSREF] [Google Scholar]
  4. Association of British Clinical Diabetologists, Primary Care Diabetes Society (2023) Glucagon-Like-Peptide 1 Receptor Agonist National Shortage. http://abcd.care/sites/default/files/2023-08/PCDS_ABCD%20GLP-1%20RA%20shortage_20230710.pdf (Last accessed: 5 September 2024.)
    [Google Scholar]
  5. Beba H, Baig S, Diggle J (2023) Prescribing pearls: a guide to sulfonylureas. Diabetes & Primary Care. 25, 2, 41-43.
    [Google Scholar]
  6. Bu Y, Peng M, Tang X et al (2022) Protective effects of metformin in various cardiovascular diseases: clinical evidence and AMPK-dependent mechanisms. Journal of Cellular and Molecular Medicine. 26, 19, 4886-4903. doi: 10.1111/jcmm.17519
    [CROSSREF] [Google Scholar]
  7. Caleyachetty R, Barber TM, Mohammed NI et al (2021) Ethnicity-specific BMI cutoffs for obesity based on type 2 diabetes risk in England: a population-based cohort study. Lancet Diabetes and Endocrinology. 9, 7, 419-426. doi: 10.1016/S2213-8587(21)00088-7
    [CROSSREF] [Google Scholar]
  8. Chow E, Clement S, Garg R (2023) Euglycemic diabetic ketoacidosis in the era of SGLT-2 inhibitors. BMJ Open Diabetes Research and Care. 11, 5, e003666. doi: 10.1136/bmjdrc-2023-003666
    [CROSSREF] [Google Scholar]
  9. Dahlén AD, Dashi G, Maslov I et al (2022) Trends in antidiabetic drug discovery: FDA approved drugs, new drugs in clinical trials and global sales. Frontiers in Pharmacology. 12, 807548. doi: 10.3389/fphar.2021.807548
    [CROSSREF] [Google Scholar]
  10. De Block CE, Dirinck E, Verhaegen A et al (2022) Efficacy and safety of high-dose glucagon-like peptide-1, glucagon-like peptide-1/glucose-dependent insulinotropic peptide, and glucagon-like peptide-1/glucagon receptor agonists in type 2 diabetes. Diabetes, Obesity and Metabolism. 24, 5, 788-805. doi: 10.1111/dom.14640
    [CROSSREF] [Google Scholar]
  11. Diabetes UK (2021) Position Statement: Low Carb Diets for People with Diabetes. http://diabetes-resources-production.s3.eu-west-1.amazonaws.com/resources-s3/public/2021-05/low-carb-diets-for-people-with-diabetes-position-statement-may-2021.pdf (Last accessed: 5 September 2024.)
    [Google Scholar]
  12. Dludla PV, Mabhida SE, Ziqubu K et al (2023) Pancreatic β-cell dysfunction in type 2 diabetes: implications of inflammation and oxidative stress. World Journal of Diabetes. 14, 3 , 130-146. doi: 10.4239/wjd.v14.i3.130
    [CROSSREF] [Google Scholar]
  13. Dormandy JA, Charbonnel B, Eckland DJ (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 366, 9493, 1279-1289. doi: 10.1016/S0140-6736(05)67528-9
    [CROSSREF] [Google Scholar]
  14. Down S (2020) How to advise on sick day rules. Diabetes & Primary Care. 22, 3, 47-48.
    [Google Scholar]
  15. Electronic Medicines Compendium ( 2020) Package Leaflet: Information for the Patient: Pioglitazone 15mg Tablets, Pioglitazone 30mg Tablets, Pioglitazone 45mg Tablets. http://www.medicines.org.uk/emc/files/pil.8836.pdf (Last accessed: 5 September 2024.)
    [Google Scholar]
  16. Electronic Medicines Compendium (2022) Glucophage 500 mg Film Coated Tablets. http://www.medicines.org.uk/emc/product/987/smpc (Last accessed: 5 September 2024.)
    [Google Scholar]
  17. Electronic Medicines Compendium (2024) Ozempic 0.5 mg Solution for Injection in Pre-Filled Pen. http://www.medicines.org.uk/emc/product/9750/smpc (Last accessed: 5 September 2024.)
    [Google Scholar]
  18. Elsevier Diabetes (2024) Glucagon-like Peptide 1 (GLP-1) Receptor Agonists and Dual Agonists. http://elsevier.health/en-US/preview/glucagon-like-peptide-1-glp-1-receptor-agonists (Last accessed: 5 September 2024.)
    [Google Scholar]
  19. European Medicines Agency (2017) SGLT2 Inhibitors: Information on Potential Risk of Toe Amputation to be Included in Prescribing Information. http://www.ema.europa.eu/en/news/sglt2-inhibitors-information-potential-risk-toe-amputation-be-included-prescribing-information (Last accessed: 5 September 2024.)
    [Google Scholar]
  20. Fonseca-Correa JI, Correa-Rotter R (2021) Sodium-glucose cotransporter 2 inhibitors mechanisms of action: a review. Frontiers in Medicine. 8, 777861. doi: 10.3389/fmed.2021.777861
    [CROSSREF] [Google Scholar]
  21. Fukuyama Y, Numata K, Yoshino K et al (2020) Euglycemic diabetic ketoacidosis due to a strict low-carbohydrate diet during treatment with sodium-glucose cotransporter 2 inhibitors. Acute Medicine and Surgery. 7, 1, e480. doi: 10.1002/ams2.480
    [CROSSREF] [Google Scholar]
  22. Gilbert MP, Pratley RE (2020) GLP-1 analogs and DPP-4 inhibitors in type 2 diabetes therapy: review of head-to-head clinical trials. Frontiers in Endocrinology. 11, 178. doi: 10.3389/fendo.2020.00178
    [CROSSREF] [Google Scholar]
  23. Gorgojo-Martínez JJ, Mezquita-Raya P, Carretero-Gómez J et al (2022) Clinical recommendations to manage gastrointestinal adverse events in patients treated with glp-1 receptor agonists: a multidisciplinary expert consensus. Journal of Clinical Medicine. 12, 1, 145. doi: 10.3390/jcm12010145
    [CROSSREF] [Google Scholar]
  24. GPnotebook (2023) Shortcut – What Next After Metformin in Type 2 Diabetes? http://gpnotebook.com/en-GB/pages/general-information/gpnotebook-shortcut-what-next-after-metformin-in-type-2-diabetes (Last accessed: 5 September 2024.)
    [Google Scholar]
  25. Home P, Riddle M, Cefalu WT et al (2014) Insulin therapy in people with type 2 diabetes: opportunities and challenges? Diabetes Care. 37, 6, 1499-1508. doi: 10.2337/dc13-2743
    [CROSSREF] [Google Scholar]
  26. Hossain MJ, Al-Mamun M, Islam MR (2024) Diabetes mellitus, the fastest growing global public health concern: early detection should be focused. Health Science Reports. 7, 3, e2004. doi: 10.1002/hsr2.2004
    [CROSSREF] [Google Scholar]
  27. Joint British Diabetes Societies for Inpatient Care (2021) Management of Hyperglycaemia and Steroid (Glucocorticoid) Therapy. http://abcd.care/sites/default/files/site_uploads/JBDS_Guidelines_Archive/JBDS_08_Steroids_DM_Guideline_FINAL_28052021_Archive.pdf (Last accessed: 5 September 2024.)
    [Google Scholar]
  28. Joint Formulary Committee (2024) British National Formulary. No. 87. BMJ Group and the Royal Pharmaceutical Society of Great Britain, London.
    [Google Scholar]
  29. Kahn SE, Cooper ME, Del Prato S (2014) Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet. 383, 9922, 1068-1083. doi: 10.1016/S0140-6736(13)62154-6
    [CROSSREF] [Google Scholar]
  30. Lee SH, Park SY, Choi CS (2022) Insulin resistance: from mechanisms to therapeutic strategies. Diabetes and Metabolism Journal. 46, 1, 15-37. doi: 10.4093/dmj.2021.0280
    [CROSSREF] [Google Scholar]
  31. Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A et al (2014) Type 2 diabetes and cardiovascular disease: have all risk factors the same strength? World Journal of Diabetes. 5, 4, 444-470. doi: 10.4239/wjd.v5.i4.444
    [CROSSREF] [Google Scholar]
  32. Medicines and Healthcare products Regulatory Agency (2017) SGLT2 Inhibitors: Updated Advice on Increased Risk of Lower-limb Amputation (Mainly Toes). http://www.gov.uk/drug-safety-update/sglt2-inhibitors-updated-advice-on-increased-risk-of-lower-limb-amputation-mainly-toes (Last accessed: 5 September 2024.)
    [Google Scholar]
  33. Medicines and Healthcare products Regulatory Agency (2024) Shortage of GLP-1 receptor agonists (GLP-1 RA) Update. http://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=103245 (Last accessed: 5 September 2024.)
    [Google Scholar]
  34. Mills E, Devendra S (2015) Steroid-induced hyperglycaemia in primary care. London Journal of Primary Care. 7, 5, 103-106. doi: 10.1080/17571472.2015.1082344
    [CROSSREF] [Google Scholar]
  35. Morris D (2022) How to diagnose and manage steroid-induced diabetes and hyperglycaemia. Diabetes & Primary Care. 24, 5,143-145.
    [Google Scholar]
  36. Musso G, Saba F, Cassader M et al (2020) Diabetic ketoacidosis with SGLT2 inhibitors. BMJ. 371, m4147. doi: 10.1136/bmj.m4147
    [CROSSREF] [Google Scholar]
  37. National Institute for Health and Care Excellence (2022) Type 2 Diabetes in Adults: Management. NICE guideline No. 28. NICE, London.
    [Google Scholar]
  38. National Institute for Health and Care Excellence (2023a) Obesity: Identification, Assessment and Management. Clinical guideline No. 189. NICE, London.
    [Google Scholar]
  39. National Institute for Health and Care Excellence (2023b) Type 2 Diabetes in Adults. Quality standard No. 209. NICE, London.
    [Google Scholar]
  40. Nauck MA, Müller TD (2023) Incretin hormones and type 2 diabetes. Diabetologia. 66, 10, 1780-1795. doi: 10.1007/s00125-023-05956-x
    [CROSSREF] [Google Scholar]
  41. Neal B, Perkovic V, Mahaffey KW et al (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. NEJM. 377, 7, 644-657. doi 10.1056/NEJMoa1611925
    [CROSSREF] [Google Scholar]
  42. Pfützner A, Klonoff D, Heinemann L et al (2017) Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapy – an emerging problem and solutions offered by diabetes technology. Endocrine. 56, 1, 212-216. doi: 10.1007/s12020-017-1264-y
    [CROSSREF] [Google Scholar]
  43. Rines AK, Sharabi K, Tavares CD et al (2016) Targeting hepatic glucose metabolism in the treatment of type 2 diabetes. Nature Reviews Drug Discovery. 15, 11, 786-804. doi: 10.1038/nrd.2016.151
    [CROSSREF] [Google Scholar]
  44. Schwartz S, Herman M (2015) Revisiting weight reduction and management in the diabetic patient: novel therapies provide new strategies. Postgraduate Medicine. 127, 5, 480-493. doi: 10.1080/00325481.2015.1043182
    [CROSSREF] [Google Scholar]
  45. Singh S, Chang HY, Richards TM et al (2013) Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Internal Medicine. 173, 7, 534-539. doi: 10.1001/jamainternmed.2013.2720
    [CROSSREF] [Google Scholar]
  46. Soccio RE, Chen ER, Lazar MA (2014) Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes. Cell Metabolism. 20, 4, 573-591. doi: 10.1016/j.cmet.2014.08.005
    [CROSSREF] [Google Scholar]
  47. Sola D, Rossi L, Schianca GP et al (2015) Sulfonylureas and their use in clinical practice. Archives of Medical Science. 11, 4, 840-848. doi: 10.5114/aoms.2015.53304
    [CROSSREF] [Google Scholar]
  48. Stewart M (2024) Initiating insulin therapy in adults with type 2 diabetes: a practical guide. Primary Health Care. doi: 10.7748/phc.2024.e1829
    [CROSSREF] [Google Scholar]
  49. Tahrani AA, Barnett AH, Bailey CJ (2016) Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus. Nature Reviews. Endocrinology. 12, 10, 566-592. doi: 10.1038/nrendo.2016.86
    [CROSSREF] [Google Scholar]
  50. TREND Diabetes (2020) Prescribing Guidance in People with Renal Impairment. http://trenddiabetes.online/wp-content/uploads/2020/08/HCP_Renal_TREND_v26.pdf (Last accessed: 5 September 2024.)
    [Google Scholar]
  51. TREND Diabetes (2022) Managing Diabetes During Intercurrent Illness. http://trenddiabetes.online/wp-content/uploads/2022/04/HCP_Illness_TREND_2022.pdf (Last accessed: 5 September 2024.)
    [Google Scholar]
  52. Uccellatore A, Genovese S, Dicembrini I et al (2015) Comparison review of short-acting and long-acting glucagon-like peptide-1 receptor agonists. Diabetes Therapy. 6, 3, 239-256. doi: 10.1007/s13300-015-0127-x
    [CROSSREF] [Google Scholar]
  53. UK Prospective Diabetes Study (UKPDS) Group (1998) Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 352, 9131, 854-865.
    [Google Scholar]
  54. Wondmkun YT (2020) Obesity, insulin resistance, and type 2 diabetes: associations and therapeutic implications. Diabetes, Metabolic Syndrome and Obesity. 13, 3611-3616. doi: 10.2147/DMSO.S275898
    [CROSSREF] [Google Scholar]
  55. World Health Organization (2019) Classification of Diabetes Mellitus 2019. http://iris.who.int/bitstream/handle/10665/325182/9789241515702-eng.pdf?sequence=1 (Last accessed: 5 September 2024.)
    [Google Scholar]
  56. Wysham C, Shubrook J (2020) Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications. Postgraduate Medicine. 132, 8, 676-686. doi: 10.1080/00325481.2020.1771047
    [CROSSREF] [Google Scholar]
  57. Xiang B, Zhao X, Zhou X (2021) Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients. Cardiovascular Diabetology. 20, 1, 78. doi: 10.1186/s12933-021-01266-x
    [CROSSREF] [Google Scholar]

Share this page

Share to Facebook Share to X Share to Whatsapp Share to Email More...

01 October 2024 / Vol 34 issue 5

TABLE OF CONTENTS

SUBSCRIBE

Journals
Related articles

Use of olaparib in BRCA mutation-positive ovarian cancer
Nurses should understand the role and purpose of the new...

Diagnosis and treatment of diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is an acute and serious...

Metformin-associated lactic acidosis
This article discusses the case of a 68-year-old emergency...

Management of pain in pre-hospital settings
Assessment and management of pain in pre-hospital care...

Managing paediatric patients with pyrexia
Pyrexia is the most common clinical complaint seen in...