LEAPS and BOUNDS: Improving Patient Outcomes Through Advances in Diabetes Mellitus Management Webinar Highlights

The knowledge regarding diabetes mellitus and its management has grown significantly over the past few years, driven by its continuing clinical relevance and its burden on patients and their families globally. Greater awareness of the different aspects of this disease led to a better understanding of its complications and their impact on a patient’s quality of life. As a result, the focus and goals of diabetes management have seen significant changes over the past few years, which are anchored on new and emerging evidence. Fortunately, newer pharmacologic agents which address these goals are now available.  

In a recent event held by Zuellig Pharma Therapeutics, in partnership with the Philippine Academy of Family Physicians and the Institute for Studies on Diabetes Foundation Inc., entitled Leaps and Bounds: Improving Patient Outcomes Through Advances in Diabetes Mellitus Management, the benefits of Dulaglutide (Trulicity), a long-acting glucagon-like peptide 1 receptor agonist (GLP-1 RA) in achieving these new goals in the management of diabetes mellitus was discussed.

Dr Rima Tandico Tan – a senior faculty at the UERMMMC Institute for Studies on Diabetes Foundation Inc. (ISDFI) and the past president of Diabetes Philippines and the Philippine Society of Diabetologists - led the discussion. She was joined by Dr Limuel Anthony Abrogena, the national director of the Philippine Academy of Family Physicians, as well as Dr Leilani A. Baldeviso, who gave her reaction on behalf of the UERMMMC ISDFI.  



Diabetes Mellitus and Cardiovascular Risk
Dr Rima Tan started her discussion by illustrating that patients with type 2 diabetes mellitus (T2DM) are two to four times more likely to develop cardiovascular diseases (CVD) compared to those without T2DM.¹ In fact, these increased CVD risks start even before the diagnosis of T2DM is made.² A significant proportion of patients with T2DM have a significant history of CVD such as stroke or heart attack, although a majority of the general T2DM population does not have a history of CVD but possesses multiple risk factors for such.³  

A Broader Focus in Diabetes Management: Updated guidelines and recommendations
Glycemic control and HbA1c reduction have been clearly demonstrated to be important in reducing the risk of cardiovascular (CV) events in patients with T2DM, as such, management of T2DM in the past focused on glycemic control. However, according to Dr Tan, the focus of T2DM management has now moved on to consider CV benefit, renal outcomes, and ultimately, long-term survival. Dr Tan further reiterates that this more comprehensive approach includes the four pillars of glycemic management, namely: glycemic management, blood pressure management, lipid management, and administration of pharmacological agents with CV and renal benefits.⁴ She also discussed in detail the most recent algorithm for T2DM management which was published by the American Diabetes Association (ADA). In the said recommendations, metformin coupled with lifestyle modification is still the first step in T2DM management. However, these recent guidelines recommend classifying patients into those with established atherosclerotic cardiovascular disease (ASCVD), those with indicators of high-risk ASCVD, and those without. As illustrated by Dr Tan, these guidelines dictate that for patients with indicators for high-risk ASCVD, specific agents with CV benefits such as GLP1RA and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are strongly recommended. ⁴ These are also in line with the most recent recommendations published by the European Association for the Study of Diabetes and the European Society of Cardiology as well as those from the American College of Cardiology and American Heart Association. Similarly, the Philippine Heart Association recommends the use of SGLT2i and GLP1RA, either alone or in combination to reduce major CV Events.   

Assessing the Evidence of Dulaglutide Benefit
Dr Rima Tan further reinforced the benefits of Dulaglutide use by providing existing and recent evidence supporting its use. Multiple studies have demonstrated that Dulaglutide provides significant improvement in HbA1c control when administered on top of SGLT2i.⁵ Considering their mechanisms of action, it is apparent that SGLT2i and GLP1RA work synergistically, accounting for the significant improvement of HbA1c which translates to reduced CV risk and ultimately better patient outcomes.⁶ Dr Tan also discussed the AWARD trials, a series of ten trials where more than 6000 patients were enrolled and showed Dulaglutide in head-to-head trials spanning the continuum of diabetes care. These studies collectively demonstrated the powerful HbA1c reduction achieved with Dulaglutide use. In these studies, 56% to 76% of patients who started on 1.5mg Dulaglutide achieved their HbA1c target of less than 7%. Furthermore, this HbA1c reduction was shown to be sustained for 104 weeks, which was the longest measuring point for the studies. Equally important were the findings of the AWARD 5 trial, which compared Dulaglutide against Sitagliptin (a DPP4 inhibitor). The study not only demonstrated the non-inferiority of Dulaglutide, but also showed greater HbA1c reduction compared to Sitagliptin, and was sustained over 104 weeks.⁷

Dulaglutide in primary and secondary prevention of CV events
Because most patients with T2DM have no previous CVD but have multiple risk factors, it is also relevant to assess the role of Dulaglutide in the primary prevention of CVD aside from its role in secondary prevention in patients with previous CVD. This evidence came with the conclusion of the REWIND Study. Dr Rima Tan highlights that the REWIND study differed from other cardiovascular outcome trials (CVOT) in that only 31% of enrolled patients had prior CVD, making the study population more representative of the general T2DM population. Although these patients had no prior CVD, they were noted to possess multiple CV risk factors at the start of the trial. The results after 5.4 years of follow-up showed a 12% reduction in CV events, which were a composite of non-fatal stroke, CV death, and non-fatal myocardial infarction when dulaglutide was compared with standard therapy. This divergence in CV risk was apparent within 1 year upon initiation of the study and was magnified as the trial progressed.⁸ This highlights the role of Dulaglutide in the primary prevention of CV events for patients with T2DM and multiple CV risk factors. 

Injectable Therapy and Patient Preference
In her discussion, Dr Rima Tan acknowledged the hesitancy among patients and even doctors in initiating injectable therapy for T2DM management, either as part of intensifying existing therapy or to achieve greater CV risk reduction. However, in a study assessing patient preference, it was found that most patients (94%) preferred the use of a Dulaglutide (Trulicity) pen and were willing to continue to use Dulaglutide (Trulicity) pen.⁹ This is essential to ensure compliance and to ensure that these benefits will translate to better patient outcomes in the real world. 

Summary
In conclusion of the discussion, Dulaglutide (Trulicity) comes in a ready-to-use pen which has been shown to be preferred by patients. Its once-weekly dosing allows for more convenient use, and more importantly, causes little to no disruption of patients’ day-to-day activities. It has superior HbA1c reduction and is the first and only GLP1 RA to demonstrate both primary and secondary prevention of major adverse CV events, backed up by recent and definitive evidence.