Change the Status Quo: New Primary Care Guidance for T2D with Co-morbidities

Becky McCall

June 10, 2020

'Easy-to-use' guidance for GPs managing patients with type 2 diabetes and various comorbidities should help to navigate the complexities of treating these patients with the wide range of medications now available.

In particular, the guidelines contain a simple, evidence-based scheme to stratify for cardiovascular risk in patients with type 2 diabetes.

Dr Samuel Seidu, GP and clinical lecturer at the University of Leicester, is lead author of the guidance produced by a committee of primary care practitioners from across Europe and the US. They intend to provide a strategy that is both evidence-based and aimed at the generalist to address the complex challenges of multimorbidity in type 2 diabetes. 

Dr Samuel Seidu

"The main difference with this guidance compared to existing guidelines is the recommendation to initiate combination therapy at the start, so tackling both glycaemic control and cardiovascular risk, not one or the other," Dr Seidu told Medscape News UK.

Prevalence of type 2 diabetes is increasing in both developed and developing countries and approximately 90% of cases are managed in primary care. Dr Seidu emphasised that, "essentially, diabetes management has become complex with the proliferation of multiple medications, and despite making sense to specialists it can be overwhelming for frontline GPs who are mainly generalists".

He added that due to the increasing complexity around medications in patients with co-morbidities, a therapeutic inertia had set in. "We need to overcome this and treat the patient not as a diabetic patient but more holistically as a patient with diabetes. This is the primary care approach."

The full guidance is published in the Primary Care Diabetes journal, with an abridged version published simultaneously in Diabetes Research and Clinical Practice.

Proliferation of Diabetes Medications Complicating Treatment in Primary Care

Various trials over the past 5 years or so have shown that diabetes medications have beneficial effects on cardiovascular health. "As primary care doctors we treat the whole patient, so if my patient has diabetes, heart failure, and kidney failure, and there's a medication to tackle all three then that's a bonus," Dr Seidu remarked. "Currently, a GP tends to manage the diabetes patient's HbA1c and may only consider blood pressure, heart or kidney problems at a later consultation due to time pressures. This situation was the key driver for the report's combination medication recommendations."

The respective committees that developed the 2018 ADA Consensus Report  and the 2019 ESC Guidelines rarely include a GP, Dr Seidu pointed out, whereas the new position statement, entitled, 'A Disease State Approach to the pharmacological management of Type 2 Diabetes in Primary Care', was developed by those in primary care for primary care and provides the only guidance of its kind.

Redefining Risk Categories – Under 40s Very High CVD Risk

Cardiovascular disease is one of the most prevalent comorbidities causally associated with type 2 diabetes and is the primary reason for mortality in these patients, Dr Seidu pointed out. He explained that the various definitions of at-risk patients were inconsistent in existing guidelines. "The EASD [European Association for the Study of Diabetes] and ESC [European Society of Cardiology] guidelines classify young type 2 patients as medium risk. We wanted to redefine the at-risk groups to two groups only. These are patients with type 2 diabetes who have very high cardiovascular risk if they have any of a number of risk factors, otherwise patients are considered at high cardiovascular risk."

The risk factors for very high cardiovascular risk include history of cardiovascular disease (CVD); multiple uncontrolled CVD risk factors including hypertension, hyperlipidaemia, obesity, smoking and/or physical inactivity; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2; albuminuria; or age under 40 at diagnosis. All other patients with type 2 diabetes are considered to be at high cardiovascular risk.

"We don't think any patient with type 2 diabetes can be at low cardiovascular risk because just by having type 2 diabetes the patient is at risk, so we do not have a low or medium risk," Dr Seidu highlighted.

With respect to the under 40 years of age risk group, the new guidance differs markedly from other guidelines. Dr Seidu explained that relatively young patients are very high risk because evidence suggests that people with type 2 diabetes have a more aggressive form of the disease, and at diagnosis they usually have more complications than patients with type 1 or matched type 2 that is controlled.

"In primary care, many of our patients are in this category," added Dr Seidu. "This age group comprises the social and economic fabric of society and if they have a stroke or heart attack then everyone suffers. To have evidence saying they have aggressive type 2 diabetes and not to classify them as very high risk and provide appropriate treatment is doing society an injustice."

The very high risk for CVD category also includes patients with type 2 diabetes who have chronic kidney disease (CKD). This is due to the fact that eGFR and albuminuria are independent risk factors for CVD, but also because there are evidence-based treatments available to manage this in primary care, noted Dr Seidu.

Type 2 Diabetes with Atherosclerotic CVD, Heart Failure, Elderly People, and Obesity

Other key recommendations involve the stratification of patients by phenotype. In those who have atherosclerotic CVD - which is the primary cause of morbidity and mortality in individuals with type 2 diabetes - the recommendations suggest initiating both metformin plus a sodium-glucose co-transporter-2 inhibitor (SGLT2i)/glucagon like peptide-1 receptor agonist (GLP-1RA) at diagnosis, Dr Seidu explained.

"We recommend initial combination therapy, which is a brave move and is different to existing guidelines, because in a patient with established CVD and type 2 diabetes there is concern not just for each separately but for both together," he said. "We want to treat with SGLT2i/GLP-1RA to help control the cardiovascular risk factors but we don't want to forget glycaemic control either and keep the HbA1c as low as possible, for as long possible. We often start these patients on statins so why not a SGLT2i/GLP-1RA plus metformin?"

However, should a stepwise approach be preferred due to concerns about side effects or cost, then metformin should be initiated first, followed by the addition of SGLT2i/GLP-1RA if the patient's HbA1c level needs further control, and the patient has established CVD.

Dr Seidu added that he expected some GPs might be concerned about side effects with combination therapy, but he notes that in the right patients, the evidence suggests the side effect profile is good. "We don't want to keep following the status quo."

In heart failure patients, the guidance recommends starting on metformin plus SGLT2i in combination rather than taking a stepwise approach, and if not, then metformin can be given first-line, and SGLT2i second-line. A similar strategy is suggested for CKD with metformin plus SGLT2i together according to the approved restrictions of dose and indications by eGFR. Metformin is an option as first-line therapy if eGFR >30 mL/min/1.73 m2, and SGLT2i to be used as second-line therapy in patients with >45 mL/min/1.73 m2 even when well-controlled on metformin alone.

Treatment recommendations for patients at high cardiovascular risk comprise initiating metformin plus SGLT2i/GLP-1RA/DPP-4i, rather than used in a stepwise approach. Metformin can be used as first-line therapy and an SGLT2i, GLP-1RA or DPP-4i as second-line therapy where cost is not prohibitive, and preference would be for SGLT2i or GLP-1RA with proven cardiovascular benefit. In obesity, metformin should be used together with a GLP-1RA/SGLT2i, again rather than stepwise.

In elderly or frail patients, the guidance is more cautious, remarked Dr Seidu. "We recommend avoiding stringent glycaemic targets that increase the risk of hypoglycaemia, so we don't suggest initial combination therapy," he explained. "We recommend metformin as first-line if tolerated, and an easy to use, safe option is a dipeptidyl peptidase-4 (DPP-4i)."

A disease state approach to the pharmacological management of Type 2 diabetes in primary care: A position statement by Primary Care Diabetes Europe. Published 10th June 2020. doi.org/10.1016/j.pcd.2020.05.004

Dr Seidu declares he has received consultancy and speaker fees from Amgen, Boehringer Ingelheim, Napp Pharmaceuticals, Novartis and Roche; advisory board, consultancy and speaker fees from AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi; and trial grant funding from AstraZeneca, Janssen Pharmaceutica, Sanofi and Servier Laboratories.

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