Both the UK National Institute for Health and Care Excellence (NICE) guidance for managing type 2 diabetes and the joint European Association for Study on Diabetes (EASD) and American Diabetes Association (ADA) consensus report released major updates in 2022 for managing hyperglycemia in type 2 diabetes.

These publications cemented a shift in approach in managing people living with type 2 diabetes, says Kevin Fernando, MSc
- We are now encouraged to think beyond glycemia and choose therapies driven by the presence of comorbidities to reduce future cardiorenal risk rather than by the traditional glucose-centric stepwise approach to managing type 2 diabetes.

Notable discrepancies exist between these publications which is why, even as a UK-based clinician, I have preferentially adopted using the joint EASD-ADA consensus report over implementing the NICE guideline in my routine clinical practice.

To be fair to NICE, the joint EASD-ADA publication is an expert consensus rather than a guideline per se and doesn't consider the impact of cost implementation to healthcare systems. These cost-effectiveness assessments by NICE have driven inconsistencies in recommendations, which I strongly feel is not always in the best interests of people living with type 2 diabetes and the delivery of evidence-based yet person-centered care.

Metformin Remains First Choice but Consider SGLT2 Inhibitors

However, both publications are consistent with firm recommendations that metformin remains the first-line pharmacologic choice for most people living with type 2 diabetes. For those with established atherosclerotic cardiovascular disease (ASCVD), who are at high risk for ASCVD, or with chronic heart failure or chronic kidney disease, sodium-glucose cotransporter 2 (SGLT2) inhibitors should be considered independent of metformin use and glycemic control, ie, A1c.  

In these clinical scenarios, NICE explicitly states to commence metformin alone initially but as soon as metformin tolerability is confirmed, introduce the SGLT2 inhibitor. In practical terms, for most individuals with the above comorbidities, I now commence metformin 500 mg once daily for 1 week then increase to 500 mg twice daily for 1 week. If metformin is well tolerated at this juncture (ie, no significant gastrointestinal disturbance), I introduce the SGLT2 inhibitor. I will then gradually increase the metformin dose over the subsequent weeks.

In my highest-risk patients living with type 2 diabetes (eg, multiple cardiovascular risk factors such as dyslipidemia and hypertension and/or significantly elevated 10-year or lifetime cardiovascular risk) I start dual combination therapy with both metformin and a SGLT2 inhibitor at the outset. Currently, most SGLT2 inhibitors are available as combination preparations with metformin to reduce pill burden.

Recommendations on the use of glucagon-like peptide 1 (GLP-1) receptor agonists significantly diverge between both publications; the EASD-ADA consensus recommendations are more proactive in positioning GLP-1 receptor agonists for glucose management, weight management, and cardiorenal benefits compared with NICE.

In the NICE guideline, GLP-1 receptor agonists appear to be an afterthought (they are placed as fourth-line agents after triple therapy with metformin and two other oral drugs). These recommendations are largely unchanged from the previous version of the NICE guideline published in 2015 despite compelling evidence to the contrary published during the intervening years.

As alluded to above, the evidence reviewed by NICE did not suggest cost-effectiveness of GLP-1 receptor agonists, hence their positioning in the management algorithm.  However, this has been vociferously challenged by many experts in the field citing an incomplete evidence base leading to erroneous conclusions.

The EASD-ADA consensus reminds us that GLP-1 receptor agonists are insulin-sparing agents and should be considered in all people living with type 2 diabetes (if not contraindicated) before insulin therapy initiation to reduce injection burden, reduce the risk for hypoglycemia, and mitigate weight gain. 

Furthermore, the EASD-ADA consensus acknowledges the cardiorenal benefits of certain GLP-1 receptor agonists and recommends their use pari passu with SGLT2 inhibitors for those living with type 2 diabetes with established ASCVD or indicators of high ASCVD risk (those aged 55 years or older with two or more additional risk factors such as obesity, smoking, hypertension, dyslipidemia, or albuminuria), again, independent of metformin use and glycemic control.

For many years now, my standard practice for those living with type 2 diabetes is to discuss lifestyle modifications: I am a big fan of the "importance of 24-hour physical behaviors for type 2 diabetes" infographic in the EASD-ADA consensus, which highlights breaking up prolonged sitting, moderate to vigorous activity, stepping, strengthening, and sleep as key lifestyle interventions. I then offer metformin and escalate therapy (as required) with an SGLT2 inhibitor followed by a GLP-1 receptor agonist.

After metformin and an SGLT2 inhibitor, the logic of offering a sulfonylurea (associated with weight gain and too high risk for hypoglycemia), or pioglitazone (associated with weight gain, peripheral and central fluid retention, and bone fractures) or a dipeptidyl peptidase 4 inhibitor (low potency and weight neutral) escapes me when compared with the compelling benefits of GLP-1 receptor agonists, which are efficacious glucose lowering agents with additional benefits of significant weight reduction (again more so than SGLT2 inhibitors) and cardiorenal protection.

Indeed, the EASD-ADA consensus states that weight loss between 5% and 15% should be a primary focus of management for many people living with type 2 diabetes and that certain GLP-1 receptor agonists (liraglutide and semaglutide) are now licensed specifically for chronic weight management independent of a type 2 diabetes diagnosis.

Finally, technology and type 2 diabetes: Both publications have opened the doors to continuous glucose monitoring (CGM) for many more people living with type 2 diabetes.

The EASD-ADA consensus reminds us that technology can be empowering for people living with type 2 diabetes but needs to be supported with high-quality education. They recommend that we consider CGM for all people living with type 2 diabetes on insulin therapy.

NICE mostly agrees with this but is more restrictive in whom we can offer either intermittently scanned CGM (isCGM) or real-time CGM (rtCGM), again largely driven by cost.

NICE recommends that we offer isCGM to adults with type 2 diabetes who are on multiple daily insulin injections (two or more daily insulin injections, which could be either a basal-bolus regimen or more than one daily insulin injection) in certain clinical situations, such as a history of recurrent hypoglycemia or severe hypoglycemia, or a requirement to self-check blood glucose at least eight times daily.

Of note, NICE recommends considering rtCGM as an alternative to isCGM if it's available for the same or lower cost. There are now rtCGM systems available via UK National Health Service prescription in the United Kingdom that fulfill this criterion.

In conclusion, both publications reflect recent seminal published evidence and contemporary management of type 2 diabetes; however, there is a notable discrepancy with respect to the positioning of the GLP-1 receptor agonist class of therapy.

Overall, because NICE guidelines hinge on cost-effectiveness of recommendations, there are inevitably restrictions or inconsistencies within their guidance, which is why I find the clinical recommendations suggested by the EASD-ADA consensus far more liberating.


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